The small intestinal ‘mysteriome’: A potentially important but uncharted microbiome

By Eamonn MM Quigley MD FRCP FACP MACG FRCPI, Lynda K and David M Underwood, Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital, Houston, Texas, USA

 

Over recent years, countless publications have documented the status of the microbiota of the gastrointestinal tract by examining fecal samples. While this approach does provide a “snapshot” or representation of what is going on in the gut, and especially in the colon, it is a crude measure of the complex interactions between micro-organisms in the gut, as well as between these same microorganisms and us (their hosts). Fecal samples comprise a terminal microbial ecosystem, characterized by depletion of readily fermentable substrates, with a concomitant change in microbial composition, even compared to those farther upstream in the colon. It is unlikely, for example, that studies using fecal samples provide a full picture of what happens when bacteria (or other microorganisms) “talk” to the lining of the gut (the mucosa) or interact with the immune system of the intestine. Even less likely is that they provide any insights into bacterial populations in the small intestine, where most of the digestion of food and absorption of nutrients takes place. The small intestine also possesses the most abundant immune tissue of the entire gastrointestinal tract.

Yet, details of which bacteria actually inhabit this long and important organ, the small intestine, are sketchy. This lack of knowledge has apparently not restricted much theorizing and speculation about the role of an overgrowth of colonic-type bacteria (referred to as small intestinal bacterial overgrowth – SIBO) in the small intestine in many symptoms, disorders, and diseases. According to one especially popular theory – the “leaky gut” hypothesis – the list of conditions is nearly endless. The “leaky gut” hypothesizes that dysbiosis in the small intestine (in other words SIBO) and a disruption of the gut barrier leads to “leakage” of bacteria and bacterial products into the circulation causing inflammation, allergy, and autoimmunity.

There are several leaps of faith involved in “leaky gut” including, of course, the definition and diagnosis of SIBO. Traditional methods of diagnosing SIBO (obtaining fluid samples directly from the upper small intestine or a variety of breath tests) are fraught with problems and, in essence, have precluded a universally accepted definition of SIBO.

Fundamental to this dilemma is the definition of the normal small intestinal microbiome – how can we diagnose abnormal when we do not know the limits of normality? I would contend that, while there are situations where it is undoubted (based on the clinical context and various laboratory and other findings) that SIBO is an issue, there are countless more instances where SIBO is over-diagnosed and incorrectly implicated as the cause of an individual’s symptoms. This is an important issue as it can lead to the inappropriate use of antibiotics – something we all wish to avoid.

There is some good news – clever techniques exist for obtaining uncontaminated fluid samples from the small intestine, a capsule technology that permits live sampling of intestinal gases (generated by bacteria) as it traverses the intestine and the application, at last, of high-throughput sequencing, metagenomics, metabolomics, and metatranscriptomics to small intestinal microbiota suggest that the accurate definition of the normal small intestinal microbiome is not far off. At that time, we can all agree on an accurate and clinically meaningful definition of SIBO.

 

Is probiotic colonization essential?

By Prof. Maria Marco, PhD, Department of Food Science & Technology, University of California, Davis

It is increasingly appreciated by consumers, physicians, and researchers alike that the human digestive tract is colonized by trillions of bacteria and many of those bacterial colonists have important roles in promoting human health. Because of this association between the gut microbiota and health, it seems appropriate to suggest that probiotics consumed in foods, beverages, or dietary supplements should also colonize the human digestive tract. But do probiotics really colonize? What is meant by the term “colonization” in the first place? If probiotics don’t colonize, does that mean that they are ineffective? In that case, should we be searching for new probiotic strains that have colonization potential?

My answer to the first question is no – probiotics generally do not colonize the digestive tract or other sites on the human body. Before leaping to conclusions on what this means for probiotic efficacy, “colonization” as defined here means the permanent, or at least long-term (weeks, months, or years) establishment at a specific body site. Colonization can also result in engraftment with consequential changes to the gut microbiota composition and function. For colonization to occur, the probiotic should multiply and form a stably replicating population. This outcome is distinct from a more transient, short-term (a few days to a week or so) persistence of a probiotic. For transient probiotics, it has been shown in numerous ways that they are metabolically active in the intestine and might even grow and divide. However, they are not expected to replicate to high numbers or displace members of the native gut microbiota.

Although some studies have shown that digestive tracts of infants can be colonized by probiotics (weeks to months), the intestinal persistence times of probiotic strains in children and adults is generally much shorter, lasting only few days. This difference is likely due to the resident gut microbiota that develops during infancy and tends to remain relatively stable throughout adulthood. Even with perturbations caused by antibiotics or foodborne illness, the gut microbiome tends to be resilient to the long-term establishment of exogenous bacterial strains. In instances where probiotic colonization or long-term persistence was found, colonization potential has been attributed more permissive gut microbiomes specific to certain individuals. In either case, for colonization to occur, any introduced probiotic has to overcome the significant ecological constraints inherent to existing, stable ecosystems.

Photo by http://benvandenbroecke.be/ Copyright, ISAPP 2019.

This leads to the next question: Can probiotics confer health benefits even if they do not colonize? My answer is definitely yes! Human studies on probiotics with positive outcomes have not relied on intestinal colonization by those microbes to cause an effect. Instead of colonizing, probiotics can alter the digestive tract in other ways such as by producing metabolites that modulate the activity of the gut microbiota or stimulate the intestinal epithelium directly. These effects could happen even on short-time scales, ranging from minutes to hours.

Should we be searching for new probiotic strains that have greater colonization potential? By extension of what we know about the resident human gut microbiota, it is increasingly attractive to identify bacteria that colonize the human digestive tract in the same way. In some situations, colonization might be preferred or even essential to impacting health, such as by engrafting a microbe that performs critical metabolic functions in the gut (e.g. break down complex carbohydrates). However, colonization also comes with risks of unintended consequences and the loss of ability to control the dose, frequency, and duration of exposure to that particular microbe.

Just as most pharmaceutical drugs have a transient impact on the human body, why should we expect more from probiotics? Many medications need to be taken life-long in order manage chronic conditions. Single or even repeated doses of any medication are similarly not expected to cure disease. Therefore, we should not assume a priori that any observed variations in probiotic efficacy are due to a lack of colonization. To the contrary, the consumption of probiotics could be sufficient for a ripple effect in the intestine, subtly altering the responses of the gut microbiome and intestinal epithelium in ways that are amplified throughout the body. Instead of aiming for engraftment directly or hand-wringing due to a lack of colonization, understanding the precise molecular interactions and cause/effect consequences of probiotic introduction will lead to a path that ultimately determines whether colonization is needed or just a distraction.

Prebiotics do better than low FODMAPs diet

By Francisco Guarner MD PhD, Consultant of Gastroenterology, Digestive System Research Unit, University Hospital Vall d’Hebron, Barcelona, Spain

Bloating and visible abdominal distention after meals is a frequent complaint of people suffering from irritable bowel syndrome, but even generally healthy people sometimes have these complaints. These symptoms are thought to be due to fermentation of food that escapes our digestive processes. Some sugars and oligosaccharides end up at the far end of our small bowel and cecum, where they become food for our resident microbes.

To manage this problem, medical organizations recommend antibiotics to suppress the microbial growth in our small intestine (known as small intestinal bacterial overgrowth or SIBO) or avoidance of foods that contain fermentable oligosaccharides, disaccharides, monosaccharides and polyols, called a low “FODMAP” diet. These approaches are generally successful in reducing symptoms, but do not provide permanent relief: symptoms typically return after the strategies are stopped.

Even worse, both approaches are known to disrupt the entire gut microbial ecosystem (not only at small bowel and cecum). Whereas a healthy microbial gut ecosystem has many different types of bacteria, antibiotics deplete them.  The low FODMAP diet deprives beneficial bacteria (such as Faecalibacterium, Roseburia, Bifidobacterium, Akkermansia, Lactobacillus and others) of the food they like to eat, and these species wane (see here).

Prof. Glenn Gibson, a founding father of prebiotic and synbiotic science, suggested that increasing ingestion of certain prebiotics could increase levels of bifidobacteria. These bifidobacteria in turn could prevent excessive gas production since they are not able to produce gas when fermenting sugars.  (Instead, bifidobacteria product short chain fatty acids, mainly lactate, which are subsequently converted to butyrate by other healthy types of bacteria, such as Faecalibacterium and Roseburia.)

Prof. Gibson’s hypothesis was tested in pilot studies where volunteers ingested a prebiotic known as galacto-oligosaccharide (Brand name: Bimuno). Healthy subjects were given 2.8 g/day of Bimuno for 3 weeks. At first, they had more gas: significantly higher number of daily anal gas evacuations than they had before taking the prebiotic (see here). The volume of gas evacuated after a test meal was also higher. However, after 3 weeks of taking the prebiotic, daily evacuations and volume of gas evacuated after the test meal returned to baseline. The microbe populations also started to recover. The relative abundance of healthy butyrate producers in fecal samples increased and correlated inversely with the volume of gas evacuated. This suggested that the prebiotic induced an adaptation of microbial metabolism, resulting in less gas.

Then researchers launched a second study, also in healthy volunteers, to look at how the metabolic activity of the microbiota changed after taking this prebiotic. They showed that adaptation to this prebiotic involves a shift in microbiota metabolism toward low-gas producing pathways (see here).

A third controlled study (randomized, parallel, double-blind), this time in patients with functional gastrointestinal disorders with flatulence, compared the effects of the prebiotic supplement (2.8 g/d Bimuno) plus a placebo diet (mediterranean-type diet) to a placebo supplement plus a diet low in FODMAPs. The study subjects were divided between these 2 diets, which they consumed for 4 weeks (see here). Both groups had statistically significant reductions in symptom scores during the 4-week intervention. Once subjects stopped taking the prebiotic, they still showed improved symptoms for 2 additional weeks (at this point, the study was completed). However, for subjects on the low-FODMAP diet, once the diet was stopped, symptoms reappeared. Very interestingly, these 2 diets had opposite effects on fecal microbiota composition. Bifidobacterium increased in the prebiotic group and decreased in the low-FODMAP group, whereas Bilophila wadsworthia (a sulfide producing species) decreased in the prebiotic group and increased in the low-FODMAP group.

The bottom line conclusion is that a diet including intermittent prebiotic administration might be an alternative to the low FODMAP diets that are currently recommended for people with functional gut symptoms, such as bloating and abdominal distention. Since low FOD MAP diets are low in fiber, the prebiotic option may provide a healthier dietary option.

 

  1. Halmos EP, Christophersen CT, Bird AR, Shepherd SJ, Gibson PR, Muir JG. Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut. 2015;64(1):93–100.
  2. Mego M, Manichanh C, Accarino A, Campos D, Pozuelo M, Varela E, et al. Metabolic adaptation of colonic microbiota to galactooligosaccharides: a proof-of-concept-study. Aliment Pharmacol Ther. 2017;45(5):670–80.
  3. Mego M, Accarino A, Tzortzis G, Vulevic J, Gibson G, Guarner F, et al. Colonic gas homeostasis: Mechanisms of adaptation following HOST-G904 galactooligosaccharide use in humans. Neurogastroenterol Motil. 2017;29(9):e13080.
  4. Huaman J-W, Mego M, Manichanh C, Cañellas N, Cañueto D, Segurola H, et al. Effects of Prebiotics vs a Diet Low in FODMAPs in Patients With Functional Gut Disorders. Gastroenterology. 2018;155(4):1004-7.

 

Additional reading:

Halmos EP, Christophersen CT, Bird AR, Shepherd SJ, Gibson PR, Muir JG. Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut. 2015;64(1):93–100.

Mego M, Manichanh C, Accarino A, Campos D, Pozuelo M, Varela E, et al. Metabolic adaptation of colonic microbiota to galactooligosaccharides: a proof-of-concept-study. Aliment Pharmacol Ther. 2017;45(5):670–80.

Mego M, Accarino A, Tzortzis G, Vulevic J, Gibson G, Guarner F, et al. Colonic gas homeostasis: Mechanisms of adaptation following HOST-G904 galactooligosaccharide use in humans. Neurogastroenterol Motil. 2017;29(9):e13080.

Huaman J-W, Mego M, Manichanh C, Cañellas N, Cañueto D, Segurola H, et al. Effects of Prebiotics vs a Diet Low in FODMAPs in Patients With Functional Gut Disorders. Gastroenterology. 2018;155(4):1004-7.

Halmos EP, Gibson PR. Controversies and reality of the FODMAP diet for patients with irritable bowel syndrome. J Gastroenterol Hepatol. 2019 Jul;34(7):1134-1142. doi: 10.1111/jgh.14650. Epub 2019 Apr 4.

 

 

The Children of Masiphumelele Township

Gregor Reid PhD MBA FCAHS FRSC, Professor, Western University and Scientist, Lawson Health Research Institute, London, Canada

Just off the main road from Cape Town, South Africa to Simon’s Town, sits Masiphumelele township where challenges of poverty, malnutrition, HIV and the risk of violence face people every day.

It is also the location for the Desmond Tutu HIV Foundation Youth Centre, a safe haven that provides adolescent-friendly sexual and reproductive health services alongside educational and recreational activities for youth living in Masiphumelele and surrounding areas.

To understand some of the dangers that children face, in 2017, about 270,000 people in South Africa were newly infected with HIV, adding to one of the highest HIV prevalence rates in the world. The Tutu Youth Centre aims at helping educate youth to reduce their risk of becoming another HIV statistic.

I was invited there by University of Cape Town Professor Jo-Ann Passmore, a woman not only recognized for her research but whose passion for helping others is reflected in her warm smile (4th from left in group photo). She asked if I would be interested in holding a workshop to illustrate to the youth how using sachets of probiotic bacteria could empower them. I jumped at the chance. On an afternoon break from the Keystone Symposium, thirty researchers joined me along with Jo-Ann and my wife Debbie, a teacher of children with learning disabilities.

After a tour of the areas where children learn on computers, play games in safety, or have personal discussions about sexual health, everyone filled the room with a stunning backdrop of the Nobel Laureate’s image. Having been privileged to meet the Archbishop when he was hosted by St. Joseph’s Healthcare Foundation in 2008, it was a nerve-tingling experience for me.

Giving a lecture on beneficial microbes is hard enough to peers sitting in the back of the room, but to do so with young South Africans was more somewhat daunting. However, it proved to be a lot of fun especially when we had to identify kids who were good leaders (the boys all pointed to a girl), who liked to make stuff and sell it to others (two boys stood out). By the end, we had picked the ‘staff’ of a new company.

The next step was for four groups to decide on the company’s name, what products they’d make from the probiotic sachets (the options were many including yoghurt, cereals, fruit juices, maize), what marketing tools they would use and who they would target to obtain a respectable income.

Interestingly, several of the conference participants seemed less engaged, as if they had never considered how microbiology research could affect real lives. In front of them were children facing huge challenges on a day-to-day basis. In one group, the kids were quiet until my wife brought out pens and paper, then they went to town designing products, names and labels. A lesson for me on how different people need different stimuli to become engaged. The faculty left early to beat the traffic back to Cape Town, so unfortunately, they did not hear the outcome of the children’s work.

When we re-assembled to present the results, I was impressed with what could be created in such a short time. My favourite was the Amazing Maize, a bottle shaped like a corn cob with the idea it would contain fermented maize. It emphasized the importance of marketing and for products to taste and look good to be purchased.

It has been over ten years since Archbishop Tutu applauded us for the Western Heads East project and thanked us for empowering women and youth and contributing to nutrition in Africa. Since then, thanks to the huge efforts of Western staff and students, and more recently IDRC funding and partnerships especially with Yoba-for-life, Heifer International and Jomo Kenyatta University of Agriculture and Technology, over 260,000 people in east Africa are now consuming probiotic yoghurt every week. The children of the South African townships were maybe too young to join in this new wave of microenterprises, but at least now they have heard about it and the importance of fermented food and beneficial bacteria.

In the background of the workshop several wonderful women committed to start up a new production unit using the Yoba/Fiti sachets developed by Yoba-for-life. I left them some sachets for them to try out the process.

But it was me who left with the biggest lesson on how precious each life is, and how those of us with the knowledge, need to provide the means for others to use their own talents to fulfill the purposes of their lives.

No better way than to start with the children.

I have IBS – should I have my microbiome tested?

By Prof.  Eamonn Quigley, MD. The Methodist Hospital and Weill Cornell School of Medicine, Houston

I am a gastroenterologist and specialize in what is referred to as “neurogastroenterology” – a rather grandiose term to refer to those problems that arise from disturbances in the muscles or nerves of the gut or in the communications between the brain and the gut.  Yes, the gut has its own nervous system – as elaborate as the spinal cord – which facilitates the two-way communication between the brain and gut.

The most common conditions that I deal with are termed functional gastrointestinal disorders (FGIDs) among which irritable bowel syndrome (IBS) is the most frequent. I have cared for IBS sufferers and been involved in IBS research for decades. But while much progress has been made, IBS continues to be a frustrating problem for many sufferers. No, it will not kill you, but it sure can interfere with your quality of life. Dietary changes, attention to life-style issues (including stress) and some medications can help but they do not help all sufferers all of the time. It is no wonder, therefore, that sufferers look elsewhere for relief. Because, symptoms are commonly triggered by food, there are a host of websites and practitioners offering “food allergy” testing even though there is minimal evidence that food allergy (which is a real problem, causes quite different symptoms and can be fatal) has anything to do with IBS. Nevertheless, sufferers pay hundreds of dollars out of pocket to have these worthless tests performed.

Now as I sit in clinic I am confronted by a new phenomenon – “microbiome testing”. I cringe with despair when a patient hands me pages of results of their stool microbiome analysis. Has their hard-earned money been well spent? The simple answer is NO! Let me explain. First, our knowledge of the “normal” microbiome is still in evolution so we can’t yet define what is abnormal – unless it is grossly abnormal. Second, we have learned that many factors, including diet, medications and even bowel habit can influence the microbiome.  These factors more than your underlying IBS may determine your microbiome test results.  Third, while a variety of abnormalities have been described in the microbiome in IBS sufferers, they have not been consistent. Someday we may identify a microbiome signature that diagnoses IBS or some IBS subgroups – we, simply, are not there yet. Indeed, our group, together with researchers in Ireland and the UK, are currently involved in a large study looking at diet, microbiome and other markers in an attempt to unravel these relationships in IBS.

There have been a lot of exciting developments in microbiome research over the past few years. One that has caused a lot of excitement comes from research studies showing that the microbiome can communicate with the brain (the microbiome-gut-brain axis). It is not too great a leap of faith to imagine how such communications could disturb the flow of signals between and brain and the gut and result in symptoms that typify IBS. We also know that some antibiotics and probiotics can help IBS sufferers. Indeed, about 10% of IBS suffers can date the onset of their symptoms to an episode of gastroenteritis (so-called post-infection IBS). All of this makes it likely that the microbiome has a role in IBS; what we do not know is exactly how. Is the issue a change in the microbiome? Is it how we react to our microbiome? Is it the bacteria themselves or something that they produce? Could our microbiome pattern predict what treatments we will respond to? These are fascinating and important questions which are being actively studied. In the meantime, I feel that microbiome testing in IBS (unless conducted as part of a research study) is not helpful.

If you are interested in our research study please contact me at equigley@nullhoustonmethodist.org

 

Related Reading:

Microbiome analysis: hype or helpful?

A clinician’s guide to microbiome testing

Here’s the poop on getting your gut microbiome analyzed

 

Where does our food come from – why should we care?

Dr. Karen Scott, The Rowett Institute, University of Aberdeen,  Scotland

The food we eat feeds our microbes, gives us energy and nutrition, and keeps us healthy. The choices we make about our food clearly affects our health, but also has a huge effect on the world around us. We need to make more effort to choose correctly.

Sometimes it seems that everywhere we look, someone has an opinion on what we should be eating. Television is full of programmes telling us how and what to cook – suitable for a range of abilities. In supermarkets we are continually targeted with special offers and promotions, encouraging us to buy things we do not need, that are not on our shopping list. In magazines there are page long adverts, letting us know many reasons why our lives will be enriched if we purchase product Y, and perhaps even how we will be missing out if we do not. Even newspapers print articles telling us which foods are “super” this week, and will endow us with youthful skin, long life, and/or a svelte figure. Next week there will be another article with a new superfood, and one demoting last week’s superfood to the “standard” food, or even demonising it completely.

Yet even with all this focus on what we should be eating, do we really care about where our food comes from? Shouldn’t we really be more concerned with the provenance and sustainability of our food, rather than whether it is “super”?

Quinoa is a grain with a high nutrient content, high protein content (including all nine essential amino acids) and is also a source of some essential micronutrients and vitamins. By popular measures, a “superfood”. Quinoa is primarily grown in South America (Peru, Chile and Bolivia) where it is an important dietary staple. The increased demand and resultant export of quinoa has contributed considerably to the Peruvian economy. On the other hand, the cost increases associated with the increased worldwide demand means that the local Andean population now struggle to afford to include this healthy food in their own diets. Additionally the enlarged land area now used for quinoa production has reduced the amount of land available to grow alternative crops, and this reduced diversity has a negative impact on soil quality and on wildlife. Not so “super”.

Another healthy food-fad with a negative environmental impact is avocado. The current demand for avocados as part of the ‘green smoothie’ revolution has resulted in considerable deforestation in Mexico to make way for avocado plantations. Avocado trees also need a lot of water, which, given that they are frequently grown in climates with problems of drought, is clearly not sustainable.

The other factor is price – we are constantly persuaded that we should be looking for the best deal, getting those “2-for-1 offers”, or buying our food in the specific supermarket “saving you the most on your weekly shop”. The reality is that we spend a smaller % of our income on food today than we ever have – and this is not because we eat less, far from it. But if we think about it, it is not the large supermarket that loses money when it introduces offers. Buy one get one free offers on, for example fruit, usually mean that the farmer is only getting paid for one of every two oranges sold. Is this fair? If you ask a people doing their food shopping if they think that milk should cost more than water – most people would say “yes of course”. Yet at the milk counter in the supermarket they automatically reach for the “special offer”, cheapest product. Sometimes the farmer gets paid less for the milk he sells the supermarket than it costs to produce. Again if you asked people in the shop if they thought this was fair, they would no doubt say no, but they still reach for the “special offer”, cheapest product. This is already driving smaller dairy farmers out of business. Is this what we want? We as consumers, as well as the supermarkets, have to take responsibility.

Similarly with meat products and eggs. Most people, when asked about the best and most humane ways to look after animals on farms, prefer the low density, outside methods often depicted in children’s story books. Yet when we reach the meat counter in the supermarket we are more likely to reach for the cheaper product than the one from the farm which assures humane conditions, but which may cost twice as much. Such farming methods are more expensive to run, so the products have to cost more. We have to make more effort to include our instinctive morality when we are actually making purchases of food.

We have also become accustomed to being able to buy anything, at any time of year. If we want to buy fruit that is out-of-season in our own country, it will be in-season somewhere else and can be flown across the world for display in our local supermarket. When we ask people if they care about global warming – most will agree that it is a big problem, threatening the world. Yet they will buy specific fruits or vegetables that have been flown 1000s of miles, in aeroplanes contributing CO2 emissions, without a thought. Locally produced food, eaten in season, completely avoids this non-essential contribution to global warming.

Feeding our microbes is easy – they just eat our leftovers. But perhaps we also need to think about them. Food produced in intensively farmed conditions contains more pesticide and antibiotic residues than foods produced less intensively. Depending where we live, imported foods may have fewer controls on additives and production methods than those produced locally. Although specific studies have not been carried out to gauge the effect of such residues on our microbes, it is likely that there will be an effect. The healthy compounds in fruits develop best when they are allowed to ripen on the bush/tree and are not harvested unripe and then transported across the world. Our ancestors ate fresh foods in season and produced locally. People living in remote areas of the modern world without access to the diverse range of foods in a supermarket have a more diverse, healthy microbiota than those of us consuming “western diets”. Our microbes do not need, and potentially do not want, intensively produced foods.

Many of us are in the fortunate position of being able to afford to pay a bit more for our food, and thus to support it being produced in the way we would prefer if we stopped to think about it. This is why we DO have to stop to think and not automatically reach for the cheapest product on the shelf.  If we do not support farmers who are producing food in the most humane way, they will go out of business and we will be left with no choice but to buy mass-produced, often imported, food. Is this really what we want?

We have become so accustomed to paying less for our food, and looking for bargains, that we seem to care less about the quality and provenance than the price. Unless we change our outlook we will affect whole populations and environments forever. We need to stop the disconnect between our thoughts about what our foods should be, and what we actually buy, and we need to do it before it is too late.

rdamicrobes

Recommended daily allowance (RDA) for microbes?

By Prof. Colin Hill, Alimentary Pharmabiotic Centre, Food for Health Ireland, University College Cork

In this months’ issue of The Biochemist (August 2018) I explored the concept of whether or not there could be a health benefit to ingesting large numbers of safe microbes in our diet (see the open access article here).  This was an effort, though I should stress not a scientifically rigorous effort, to consider the long history of encounters between humans and ingested microbes.

This opinion piece was prompted by a series of open questions which have often puzzled me.  Why is so much of our immune system focussed on the gut?  Why not simply let the microbes and food constituents pass through and get digested without such strict surveillance?  Surely it would be more metabolically favourable to only react to those microbes that breach our epithelial barriers?  Why does our enteric nervous system devote so much of its resources to the gut?  Why is there a generally beneficial effect of many probiotics across so many health conditions?  Why is mother’s milk designed to promote the growth of microbes?

Could the solution to all of these questions be down to a very simple answer? Because the gut ‘expects and requires’ constant encounters with microbes for full functionality. Given that humans evolved into a microbial world, and that we have consumed a diet rich in microbes for most of our evolutionary history, it makes sense that our enteric systems would be designed to appropriately deal with microbes of all types, selecting out those which can cause damage and destroying them, accommodating those which will become part of our microbiomes and letting the rest pass through.  Surely we are monitoring and controlling our ‘microbial’ organ in the same way that our eukaryotic organs are monitored and controlled.

Could it be that the rise in autoimmune diseases could be, at least in part, due to an immune system primed to expect more microbes than it currently sees?  Should we recommend that a daily dose of safe microbes should be included in dietary guidelines – in the form of more safe raw foods, more fermented foods and more probiotics? It must be emphasized that some serious pathogens must be controlled or eliminated from food – not ALL live microbes are safe. But the goal can be to process only when needed for safety reasons, so foods can be a source of the safe microbes they harbour.

Lots of questions, and not many answers.  But I for one am taking account of this concept in my daily diet and am deliberately eating more microbes – I’ll let you know how it goes!

Talking Science with ISAPP’s Science Translation Committee

By Christopher Cifelli, PhD, VP of Nutrition Research, National Dairy Council.

Communicating with others is an essential part of everyday life. We are constantly sharing information about a variety of topics with friends, family, and even strangers. Most of the time the interaction is easy and natural – and sometimes even fun. But, have you ever talked to a scientist or asked a scientist a question?

Scientists love to talk about their research. And, other scientists want other to know about their research. They enjoy expounding on the minute details of their work and can spend hours on the littlest detail. That is one trait that makes a scientist effective – the attention to detail needed to posit hypotheses and then experimentally test them in controlled, thought-out manners. Scientists can talk to other scientists easily – but, ask some of them to explain their work to the average person and it doesn’t always go so well.

ISAPP is composed of scientists that are world-renowned experts on probiotics, prebiotics, and fermented foods. And, like other scientists, ISAPP wants others to know and understand these complex topics so that they can make informed decisions that may benefit their health. The question was – how does ISAPP do that? The answer: focusing on effectively translating the science. I offered ISAPP my leadership of a new committee to take on this task. ISAPP formed the Science Translation Committee nearly 3 years ago with a goal of taking complex scientific topics and making them easy to understand for consumers and health professionals. The result of this effort has been the development of numerous infographics, blog posts, and informational videos that translate years of research into easily digestible nuggets of information that people can use. The most recent infographic focused on dispelling some common myths about probiotics – because, who doesn’t like some myth busting!

Effective science communication is essential – essential because it can help people understand the complex and enable them to make choices that can benefit their overall health. ISAPP – which is grounded in science – will continue to be the voice of probiotic and prebiotic science and work to help people understand these fun and interesting topics. So, check out our website and our resources and start learning!

blog foodomics image

Global FoodOmics: A Crowd-Sourced Window Into Microbes In Our Foods

January 25, 2018. By Mary Ellen Sanders, PhD , Dairy & Food Culture Technologies

Among the factors under our control, diet may be the most important determinant of our gut microbiota. Observations from the American Gut Project suggest that foods containing live microbes increase fecal bacterial diversity, which is generally associated with a healthy gut.

An initiative, Global FoodOmics, was launched earlier this year at the University of California San Diego under the auspices of the American Gut Project to learn more about bacteria in foods and the small molecules they produce. Dr. Julia Gauglitz is the project manager. Food samples (over 2000 have been collected to date) have been analyzed for their small molecule composition and will be tested by 16S rDNA sequencing to determine the bacterial species present. Although currently in its early stages, the aim for this project is to inventory the vast different foods consumed by people around the world.

Although many fermented foods (beer, bread, wine, kefir, many cheeses and others) rely on yeast or molds as fermentation or ripening agents, this project will aim to detect bacterial DNA, but these DNA approaches cannot distinguish between life and dead bacteria.  Labels and other descriptors accompanying submitted food samples may help determine if the species detected are likely to be alive. Fermented foods that retain live bacteria are more likely to influence our colonizing microbiota.

The small molecules being assayed are not limited to the ones produced by microbes. They may be due to microbial growth in the food (by food fermentation microbes or perhaps by spoilage or food poisoning microbes), may be innate to the food, or may be intentional or incidental (e.g., pesticides) additives to foods.

The intent is to turn Global FoodOmics into a crowd-sourced project. It will join the American Gut Project as an avenue for citizens to directly participate in science and enable the project to make all of the data publically available to other researchers and clinicians.

It is notable that this project is not the first attempt to understand the microbial components of food. Food microbiologists for decades have been assaying foods for microbes used to produce food, responsible for food spoilage and linked to food poisonings.  Recently, Prof. Bob Hutkins, University of Nebraska, on behalf of the International Scientific Association for Probiotics and Prebiotics (ISAPP) and with support from the National Dairy Council, embarked on a project to learn the state of knowledge about levels of live microbes in fermented foods. They dug into the published literature and emerged with “A survey of live microorganisms in fermented foods”, In Press at Food Microbiology. This paper gives us a summary of what is known about populations of live microbes in fermented foods, information that is very useful for people wanting to add live microbes to their diet.

Another effort to understand microbes in foods is the Consortium for Sequencing the Food Supply Chain, a partnership between IBM Research and Mars Inc. This project, focused on food safety, aims to develop a baseline of normal microbial communities in foods.

Both Global FoodOmics and the Consortium for Sequencing the Food Supply Chain will leverage modern DNA sequencing technologies to allow us better understand the microbes associated with foods. Global FoodOmics is the first project to understand the microbes and molecules in foods, by pairing small molecule metabolomics measurements with rDNA sequencing.

stool sample for lab

Microbiome Analysis – Hype or Helpful?

September 2017. By Karen Scott, PhD, Rowett Institute, University of Aberdeen, Scotland.

Since we have realized that we carry around more microbial than human cells, and that these microbial inhabitants are important to maintain our health, searching for the bacterial species that are implicated in causing disease has become the holy grail of microbiology. However, to understand which bacteria are unnaturally present or absent in a disease state, we first have to understand what constitutes normal. This is hampered by the fact that we are all different – and our microbial communities are also all different. In fact, the faecal bacterial community in samples taken months apart from one person will be identifiable as coming from that specific healthy adult, but the community will be quite distinct from samples from any other healthy adult. In the same way, the microbial community of two individuals suffering from the same disease will be different.

Despite these differences, scientists have managed to establish some facts over the past 15 years. Too many Proteobacteria, which includes Enterobacteria and E.coli, in your large intestine is not generally good news. Firstly, it means that conditions in the large intestine are probably not as anaerobic as they should be. Secondly, an expansion in these populations usually means a decline in something else – after all food and places to live are finite resources. Bacterial diversity in the adult intestine is also important. The main factor that has been found across many different diseases is that bacterial diversity is lower in diseased individuals than their healthy counterparts. This does not necessarily mean that a low diversity is causing the disease, as various features of the disease (including any antibiotic therapy, inflammation, decreased or increased transit time) may all themselves affect the diversity of the microbiota.

Although scientists have not succeeded in defining a ‘healthy microbiota,’ there is an increasing trend to get your microbiome tested. Entrepreneurial microbiome companies are bombarding us with offers to “send in a small sample and find out about your gut microbiota”. All of course, for a ‘reasonable’ price. So, should you?

This really depends why you want to know, and what level of detail of analysis is being offered. Remember the orders of taxonomy? Kingdom, phylum, class, order, family, genus, and species.  Some companies identify the bacteria in your faeces only to the phylum level. This is a taxonomic level above the level needed to differentiate mammals and fish (these are ‘classes’). If you told someone that there were more fish in the Indian Ocean than mammals would this be a surprise? It would be such an expected fact it would be meaningless. This is similar to describing the microbiota at a phylum level – Bacteroidetes numbers versus Firmicutes numbers. Such numbers are meaningless. However, continuing the fish analogy, if you said that there were more mackerel than tuna in the North Atlantic Ocean this becomes a bit more meaningful. The fisherman immediately knows what type of fish he is more likely to catch, and perhaps even which net to use. The same is true of the microbiome. Telling someone that he/she has a lot of Enterobacteria and few Roseburia is actually useful as we know from studies that this represents an abnormal balance of bacteria and something should be done to redress this. Yet the bottom line health consequence of this abnormal balance of bacteria remains to be determined. So getting your gut microbiome sequenced could be useful – depending on what level of information you will receive, and what you are prepared to do about it.

And so we come to the next problem. Having established what your gut microbiota is, how are you going to make it better? And will that make YOU better? At the moment scientists don’t really have a good answer to these questions. Specific prebiotics can certainly be useful to increase the numbers of some bacteria generally assumed to be beneficial – such as Bifidobacterium, Faecalibacterium prausnitzii and even Roseburia species. But it is not really clear what the exact health benefits of such an increase in bacterial numbers would be. Health claims on prebiotics are currently limited to ‘improve intestinal transit’ and ‘lower the glycaemic response’. If you found out that your microbiota had a low diversity, increasing the variety of foods in your diet, in particular the fibre component, could certainly improve this. Our gut microbiota basically relies on our undigested food to survive, so providing a greater amount and more types of food containing fibre and prebiotics will definitely encourage populations of diverse bacteria to expand. In addition to improving digestive health, fibre fermentation by gut bacteria also results in the production of microbial products that have been shown to have health benefits.

So by all means get your gut microbiome analyzed if you want to, but perhaps instead, save your money and just increase your prebiotic and fibre consumption, which will increase levels of the potentially beneficial bacteria that are already there in your gut.

brain-gut relationship illustration

Bugs on the Brain: the Microbiota-Gut-Brain Axis

September 2017. By Eamonn M. M. Quigley, Chief Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Professor of Medicine, Weill Cornell Medical College, Houston, Texas, USA.

We can all remember those instances of diarrhea (or at least frequent bowel movements) and “butterflies” that we suffered before a critical test, interview or presentation. These are examples of stress originating from the brain influencing gut function. Extensive research over the past several decades has revealed that this is a two-way street – the gut constantly signals to the brain, too. This bidirectional channel of communication between the “big brain” in the cranium and the “little brain” (i.e. the enteric nervous system) in the gut came to be referred to as the gut-brain axis. This link relies on neurons of the sympathetic and parasympathetic nervous systems, as well as circulating hormones and other neuromodulatory molecules.

We now understand that mental symptoms of stress, anxiety or depression have a clinical impact on the gut. These include situations where the brain, the gut and their channel of communication, the autonomic nervous system, are affected by the same pathologic process. Parkinson’s disease is a prime example. Indeed, a hypothesis has evolved to suggest that Parkinson’s disease actually originates in the gut and ascends to the brain. Other scenarios include those instances where neurologic symptoms are a consequence of a primarily gastrointestinal pathology. This occurs in malabsorption syndromes when nutrients such as folic acid and B12, which are critical to brain function, become deficient. Finally, and most commonly, are those situations such as irritable bowel syndrome (IBS) where it is widely believed that symptoms result from dysfunction or disturbance somewhere along the gut-brain axis. In some individuals the problem may lie primarily in the gut; in others the main issues may be a distorted representation of gut stimuli in the brain.

Recently the concept of the gut-brain axis has been extended to include the microbiota (the microbiota-gut-brain axis) and tantalizing evidence suggests that bacteria resident in the gut could have an impact on the “big brain”. Indeed, some researchers have raced ahead to suggest that assessing alterations in the microbiome could assist in the diagnosis of a host of neurological disorders and that therapies targeted at the microbiome could play a central role in disorders as diverse as Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, autism, stroke, depression and drug addiction.

We should remember that the microbiota-gut-brain axis is far from a novel concept as it was clearly described over 60 years ago with research on hepatic coma. Metabolic products of gut bacteria lead to this much feared complication of advanced liver disease and an intervention targeted at the microbiome, namely, the administration of antibiotics, was shown to be dramatically effective. In these pioneering studies the role of bacterial overgrowth in the small bowel by coliforms and other bacteria, which are normally confined to the colon, was found to be important. Subsequently, these same bacteria and the inflammatory response that they evoke have been incriminated in the pathophysiology of another common consequence of chronic liver disease, portal hypertension, as well as in other complications such as spontaneous bacterial peritonitis, systemic sepsis and hemostatic failure. Indeed, there are several manifestations of this tripartite resonance between microbiota, the liver and the central nervous system. Gut health factors such as small bowel bacterial overgrowth, an abnormal microbiota, impaired gut barrier function, a pro-inflammatory state and the appearance in the systemic circulation of neuro-active molecules generated by bacterial metabolism are all postulated to play important roles in the actual pathogenesis of a number of common liver diseases. So what is new?

From the basic science laboratories and a variety of animal models a pretty coherent message has emerged. Firstly, the microbiome can influence brain development, structure and function and lead to changes in cognition and behavior. Secondly, the manipulation of the microbiome – for example, with probiotics – can ameliorate certain brain disorders and reverse impaired function. Thirdly, the inoculation of microbiota samples from individuals with a number of neuropsychiatric disorders into animal models can recapitulate features of the human disease. So far so good.

As always, extrapolation from animal studies to humans is fraught with difficulties: differences between animal and human brains and microbiota, the limitations of animal models of psychiatric and functional bowel disorders, and, above all, the challenges of studying brain function in humans. The good news is that these challenges are being addressed. Researchers are utilizing various technologies that provide dynamic images of brain function in various parts of the brain in response to a variety of situations, stimuli and exposures. These are now beginning to provide evidence that our microbiota can influence brain function and that the gut microbiota might, indeed, be a therapeutic target for patients with disorders such as depression, Parkinson’s disease and autism. Data are preliminary and certainly not at a stage where we can offer diagnostic testing based on a fecal sample or recommend antibiotics, prebiotics, probiotics or fecal microbiota transplantation for a given neuropsychiatric disease or disorder. But watch this space!

kombucha

Kombucha: Trend or New Staple?

September 2017. By Prof. Bob Hutkins, Khem Shahani Professor of Food Science, University of Nebraska, Department of Food Science and Technology, Lincoln.

This blog post is adapted from a piece published by the Lincoln Journal Star. The article, first published May 4, 2016 and written by Prof. Bob Hutkins, appeared as a response to a reader’s question: “I keep hearing about kombucha… What is this stuff?”

Kombucha (pronounced kom-BOO-chuh) is made by fermenting sweetened tea using a combination of yeasts and bacteria. This mixture of live cultures that starts the fermentation is called SCOBY, short for “symbiotic colony of bacteria and yeast.” The SCOBY takes the form of a gooey mat that can be re-used for each batch or shared with friends.

Kombucha is one of many trendy fermented foods, like kimchi and kefir, that are now found everywhere. No longer just the fare of hipster cafes and posh restaurants, you can find kombucha at your local grocery store—or even at Walmart.

Kombucha’s origins go back at least 2,000 years, to China; the drink gradually spread throughout Asia and Europe. In the U.S., kits for home-brewing kombucha became available to consumers in the early 1990s, and bottled versions soon appeared on grocery store shelves.

Several factors may explain the popularity of kombucha. First, many people like the flavor: uniquely sweet and sour, with a vinegary overtone. Some ethanol (alcohol) may also be present, although commercial products must contain less than the legal limit of 0.5 percent. The fermentation reaction yields carbon dioxide, which gives kombucha a pleasant fizziness. Flavor combinations are endless, from ginger, mango, and blood orange to lavender and cinnamon.

It’s probably the suggested health properties that are most responsible for the kombucha craze. The live cultures in some blends have antimicrobial activity, which may have been valuable in past eras when antibiotics were not available. However, these properties depend on the particular mix of microbes, which varies from batch to batch or brand to brand. Other suggested health benefits range from improved gut health and digestion to treatment of cancer and other diseases. Unfortunately, there is no scientific evidence to support these health claims.

It may be that kombucha is not for everyone—the acidic nature of the drink may not sit well for some people. Microbiologists have also expressed concern that home-brewed kombucha could possibly contain toxin-producing fungi. (See related post on making safe fermented foods at home.)

Nonetheless, there’s no doubt that many consumers are drinking kombucha. Annual sales in the U.S. are over $500 million, with double-digit growth. Around half of the coveted 25-to-34 age group (i.e. millennials) are kombucha drinkers. Yes, it’s popular now, but it also seems that kombucha is likely to be around for a while.

 

Bob Hutkins is the Food Doc. He is a professor at the University of Nebraska-Lincoln, where he teaches and conducts research in food science and food microbiology. Questions on any topic related to food, food safety, food ingredients and food processing can be sent to the Food Doc at features@nulljournalstar.com.

bowl of yogurt with strawberries

Advice from a Nutritionist:  Eat More Fermented Foods.

September 2017. By Christopher Cifelli, PhD, VP of Nutrition Research, National Dairy Council.

Whenever I tell someone that I have a degree in nutrition science, I usually get asked, “Are carbs bad?” or “Should I avoid added sugars?” Rarely do I get asked “What should I be eating more of?” While vegetables, fruits, dairy and whole grains would all be perfectly suitable answers to that question, my go-to response is fermented foods.

Fermented foods have been around for thousands of years. Fermentation is the process of using specific microbes – for example, bacteria, yeast, and molds – to transform one food into another. For example, the fermentation process transforms milk into yogurt. Fermented foods are unique because they can contain live microbes, which can confer health benefits beyond simple nutrition. For instance, did you know that the microbes in fermented foods can help inhibit pathogen growth in the gut? Or, that eating certain fermented foods, such as yogurt, is associated with reduced chronic disease risk?

Government organizations across the globe provide dietary recommendations to help guide people choose the type of foods or diets that promote health. Commonalities include eating more fruits, vegetables, whole grains, beans, legumes and dairy. Another commonality – albeit a disconcerting one – is the lack of a recommendation for consuming fermented foods even though fermented foods, including red wine, kimchi, soya, and yogurt are key parts of healthy diet patterns.

Several recent publications have discussed the need to encourage the consumption of foods that can directly and beneficially impact our gut microbiota to improve overall health (e.g., Bell et al. or Gordon et al.). Identifying and consuming foods that can selectively impact the microbiota to benefit the host health should be a priority.

The time is now. Health professionals should review available evidence to determine how fermented foods fit into dietary recommendations to promote a healthy microbiota. They should encourage the public to increase their consumption of fermented foods to support the health of their microbiota and body. That way, the next time any of us are asked “What should I be eating” we can point to dietary recommendations and say — Fermented Foods!

Read more on fermented foods here and here.

Bacteria illustration

Suggestions for Making Safe Fermented Foods at Home

September 2017 – By Drs. Bruno Pot and Frédéric Leroy, Vrije Universiteit Brussels, Brussels, Belgium.

The impact of lifestyle on the composition and diversity of the human gut microbiota over the last five decades has been tremendous. This is thought to be mainly the result of a cumulative effect ascribed to the increased use of antibiotics and other drugs as well as dietary changes, including consuming less fermented foods that contain live microorganisms.

Fermented foods are important for a healthy diet, as they have the potential to improve the microbiota quality and diversity, are related with reduced disease risk, and can provide essential nutrients.  Consumers are constantly being informed about these benefits, leading to pleas for a return to home-made fermented foods. However, there is rarely mention of the risks that home-made natural fermentations can entail. While making fermented foods at home can be a good idea and help you consume more beneficial microbes, we should realize that the empirical knowhow, skills and equipment to make safe food fermentations may have disappeared over time. This blog is a gentle warning about the possible risks of non-controlled fermentations.

  • Use a starter culture: The use of specific starter cultures at sufficiently high concentration is recommended to properly initiate the fermentation of specific foods and to obtain sufficient control over the process. Relying on spontaneous fermentation (i.e., hoping that environmental bacteria or yeasts initiate the fermentation) increases the risk that uncontrolled fermentations by unsuitable bacteria, yeasts and molds will result in bad or variable quality. In the worst case, dangerous end-products will be obtained.
  • Twice is nice: Starters should not be used repeatedly. Because bacteria multiply several times per hour, their genetic material is changing continuously and the quality of the starter will change over time. It is therefore not a good idea to re-use your ‘old’ product to restart a ‘new’ fermentation all too often, although some fermented food ecosystems such as sourdough or water kefir may usually be ‘backslopped’ frequently. The risks are that off-flavours will be formed or that acidification, which protects your food against the growth of spoilage or pathogenic bacteria, will be too slow.
  • Choose wisely: Not all starters are necessarily safe, although commercially available ones should in principle have been checked for safety (See Helpful Information links below for guidance on findings the right starter). Some yeasts and lactic acid bacteria (LAB) can form compounds (for example, biogenic amines from amino acids) that can result in many health troubles like headache, blood pressure drops, diarrhoea, and even heart problems. You can avoid the production of biogenic amines by using selected starters that do not have the metabolic machinery to make them.
  • To breathe or not to breathe: Some fermentations, like the production of water kefir (usually using dried figs), should be performed in the absence of air and thus require a rubber sealing. For other fermentations, a complete submerging in brine or a covering with oil is necessary. Kombucha, on the contrary, needs a wide opening covered by a cloth that allows oxygen into the vessel. Uncontrolled anaerobic conditions can increase the risk for the growth of clostridia. In cheese making they can be the cause of cheese blowing up, in other conditions they may produce the deadly botulin toxin.
  • Avoid Moulds. Moulds are another problem linked to (too much) oxygen. Moulds can make mycotoxins which can make one very sick and any visible contamination should ring bells! It is not wise to scrape them off, as often they have produced toxins already, left spores or will remain present through their ‘roots’ which most of the time are not visible.
  • Hold the alcohol: During fermentation, sugars are converted to lactic and acetic acids, but also to ethanol. Therefore, the concentration of sugar added may impact the final alcohol levels of the end-product.
  • Pass the gas: In the case of water kefir, the use of a water lock can be necessary, as the CO2 gas which is formed during the fermentation may increase the pressure in the vessel, leading to potential breaking or surprises during opening. Therefore, blown fermented foods products should never be consumed.
  • Party crashers and acid balance: Not all bacteria are your friends. Some undesirables can be present on fresh vegetable products and can in themselves lead to spontaneous fermentation. Therefore, it is important to not let your fermentation be hijacked by these bacteria. The good bacteria should grow and produce acid quickly for a safe fermentation. Pathogens generally cannot grow in high acid environments (below pH 4 is a safe target). This acidity should be reached as quickly as possible during fermentation to avoid the growth of bacteria which can produce toxins or off flavours.
  • Nothing lasts forever: While high acid is essential, it does not protect the food indefinitely. Some yeasts and fungi can grow in high acid. As they grow, some can reduce acidity locally so that (mainly at the surface) other (potentially pathogenic) bacteria can develop
  • Use good quality raw materials. Use only good quality and fresh ingredients when deciding to ferment. While fermentation helps to preserve your fresh foods longer, it will not rescue (almost) spoiled products!
  • Summer and winter milk. If you use milk in your fermentation, it is also possible that the quality of the end product will be different along with the season, as summer milk, harvested from cows in the field, has a different composition from milk harvested from cows fed winterfeed.
  • Temperature. Temperature control is important. While for sauerkraut room temperature 18-22 (65-72°F) is fine, yoghurt fermentation is much better at 37°C (100°F). You, therefore, can expect differences in summer and winter if you do not control the temperature. Find the right spot in the house for both summer and winter.
  • Water activity. In addition to acidification, microbial control is often achieved by reduction of the water activity, generally by sufficient salting and/or drying. This is of major importance to produce fermented sausages. It is important to point out that raw meat is a particularly hazardous matrix, requiring even more care and attention when performed at home.
  • Salt and acetic acid (vinegar) concentration. Both ingredients help keep the pathogens at bay. Stick to recipes that have proven to be reliable.
  • Fermentation time. This is an important factor which can vary a lot and, in turn, impact the quality of your end product. Its critical nature is well known from wine making, in which the duration of the primary and secondary fermentation is well known to be crucial to the quality of the result. While in wine the primary fermentation usually takes between 3 to 7 days, the secondary fermentation can take much longer and will depend on the vial, the alcohol concentration and the yeast used. The fermentation of sauerkraut goes in three stages. ALL three are essential for a safe and tasteful product; a minimum of three to four weeks is necessary. Industrially produced yoghurt can be made in 8 hours, but at home it may take a few hours more. How much more again depends on the milk quality, the starter and the temperature.
  • Do’s and don’t’s: Do invest in a kitchen weighing scale and a thermometer that goes from 0 – 100 °C. Don’t even think about home-made sausage.  Don’t even think about raw-milk cheese.  Do start with simple foods like yogurt or kefir.  There are fool-proof kits for making beer (although they require some hardware).  Sauerkraut and kimchi are relatively easy to make.

Being aware of these simple concepts can help ensure the production of a healthy, tasty fermented food. Consumers should expect that the quality of the resulting fermented food will vary from lot to lot and they should be able to judge when a product is still safe for consumption and when it is not. Consumers should also be aware of the risk factors above and know how to select and handle equipment and execute procedures that will yield safe and nutritious end products.

For additional information:

Fermented Foods on the www.ISAPPscience.org website.

Preparing Fermented Foods and Pickled Vegetables

The University of Georgia Cooperative Extension, the National Center for Home Food Preservation

Safe Preserving: Fermented Foods From the University of Wisconsin Extension

probiotics bottle

Ever evolving microbial friends – new microbes that could impact health

May 2017. By Prof. Seppo Salminen, Director of the Functional Foods Forum, University of Turku.

Bacteria have been part of our life and part of human nutrition since ancient times. Microbes have a variety of essential roles in fermentations and other production processes, as reviewed by Marco et al (2017). Generally, the bacteria used in fermented foods have a very long history of safe use.

Traditional probiotics, such as species of Lactobacillus and Bifidobacterium, are deemed safe for our food supply, for providing certain nutritional support and as supportive agents for medical treatments. Pediatric and gastroenterology organizations recommend specific Lactobacillus, Bifidobacterium and Saccharomyces probiotics for different benefits, including treatment and prevention of acute pediatric gastroenteritis, antibiotic-associated side effects and diarrhea (ESPGHAN, WGO). Currently, probiotics appear more effective in infants and children than in adults and elderly. Thus, there is a need to continue to develop new probiotic tools for nutrition and medicine especially for adults and the elderly.

New non-traditional species of bacteria being researched for their health benefits are now being proposed for use in foods. These have to be assessed for safety as novel foods or ingredients for food production. With the new regulation in Europe, it is sometimes challenging to find the road to market. In European Union, the novel food legislation has just been revised (EU 2015), applying also to the safety assessment of novel microbes. Two novel microbes have recently been approved in the EU:  Clostridium butyricum and Bacteroides xylanisolvens (the latter only in heat-treated form).  Both approvals concern only safety assessment; health claim applications may be expected later.

Clostridium butyricum has been used as a probiotic in Japan and many other countries, but in Europe, its classification as probiotic without a health claim is unlikely. This is not due to anything unique about C. butyricum, but due to the word ‘probiotic’ being considered a health claim requiring authorization. Bacteroides xylanisolvens in its heat-treated form does not fit the definition of probiotic (Hill et al 2014) as no viable bacteria are present in the product.

Taken together, opportunity exists today for the development of new microbial tools for foods, nutrition, supplements and pharmaceutical targets.  Several research paths are underway, likely resulting in new novel food applications and safety assessments. For example, Akkermansia muciniphila a normal, human colonizing microbe, has shown benefits for obesity-related metabolic effects, but so far only in mice (Gomez-Gallego et al 2016, Plovier et al 2017). Human studies are underway. Animal studies suggest that Faecalibacterium prausnizii treatment may improve hepatic health, and decrease adipose tissue inflammation in mice and these results warrant further studies to discover the therapeutic potential in humans (Munukka et al 2017). However, safety assessment is an essential part of future work for these novel probiotics and the human intervention studies are required to understand the role of novel microbes in health and disease. Thus, there are a lot of challenges for both researchers and the industry to uncover novel effective and safe microbes for future foods and drugs.

fermented foods

That bacteria in your food — It may not be so bad

April 2017. By Chris Cifelli, PhD, VP of Nutrition Research, National Dairy Council, Rosemont, IL.

Bacteria and food. For most people, those two words never belong in the same sentence and, when they do appear together, immediately conjure thoughts of contamination, spoilage, food poisoning, and worse. It is true that unwanted microbes can ruin good food and make us sick if proper food handling procedures are not followed. But what if there were unique situations where food and bacteria did belong together? What if certain microbes could help transform milk, cabbage, cucumbers, grapes, and more into wondrously delicious and healthy foods? This idea is not that farfetched. Quite the opposite – it’s called fermentation and it’s been around for thousands of years.

Fermentation is the process of using specific microbes – for example, bacteria, yeast, and molds – to convert one food to another. Some examples? Milk can be changed into natural cheeses and yogurt. Cucumbers are transformed into pickles. Fermenting cabbage yields kimchi and sauerkraut. Grapes are converted into wine. Some of our most recognized foods are the products of fermentation. What are the benefits of these changes? First, fermentation creates new textures and flavors that increase palatability. Second, fermentation was, and in certain parts of the world continues to be, an important tool for converting a very perishable food into something that has a longer shelf-life. Finally, fermented foods are good for your overall health. For example, fermented foods:

  • Represent a safe way to increase our consumption of live microbes
  • Provide key nutrients as the microbes used in fermentation can make certain essential vitamins
  • Can help inhibit pathogen growth in the intestine
  • Can reduce the risk of developing certain chronic diseases. The most studied has been yogurt, which is associated with less weight gain and reduced risk for cardiovascular disease and type 2 diabetes.

Healthy, balanced diets should include live microbes. Adding fermented foods to your diet is an easy and delicious way to accomplish that. So – next time you think of bacteria and food together maybe you’ll think of a winning combination that can improve health!

happy and sad microbiota

You Have the Microbiota You Deserve!

March 2017. By Colin Hill, PhD, APC Microbiome Institute, School of Microbiology, University College Cork, Ireland

Your microbiota has been selected stochastically from all of the microbes you have encountered during your life, from or perhaps even before your birth. It has also been modified by a number of variables, including your genome, your birth mode, your diet, your health status, your environment and many other factors. At this moment in time it is in a particular configuration as a result of your multiple encounters with nature and nurture. It is unique to you, and hopefully it is relatively stable and resilient. However, if you change your diet significantly, take antibiotics, become unhealthy or regain health, lose or gain weight, move to a less or more developed country, your microbiota will also change. So, at what point is your microbiota optimal and at what point is it sub-optimal and perhaps contributing to ill-health – a state often referred to as ‘dysbiosis’?

Dysbiosis is a very loaded term; ‘dys’ is defined as a combining form meaning “ill” or “bad”, implying that the microbiota being described is actually causing harm. Can we really say that any particular microbiota is ‘ill’ or ‘bad’? Maybe, to paraphrase Tolstoy’s comment on families, we can say that in healthy individuals all microbiotas are optimal, but that in unhealthy individuals all microbiotas are dysbiotic in their own way. But this is instinctively unsatisfying, and means that the term has little value as a scientific descriptor. It becomes even more confusing if we consider your microbiota and my microbiota – your beneficial microbiota could well drive disease in me and therefore be considered dysbiotic, even though we could share many characteristics, including our general health or disease status.

But suppose you have a relatively stable gut microbiota and your doctor prescribes a broad spectrum antibiotic. Your microbiota is disrupted and within a few days you succumb to antibiotic associated diarrhoea – surely we can refer to this as dysbiosis? Well, maybe not. It could be argued that disrupted microbiota may well be appropriate for someone following antibiotic treatment – and perhaps diarrhoea may well be the correct evolutionary response to a massive microbial disruption? Perhaps we have evolved to react to a substantial change in the gut microbiota with a version of colonic irrigation to ‘purge’ the system and accelerate the return to a stable diverse microbiota.

It could be reasoned that there are other instances where the term ‘dysbiosis’ might be useful. Consistent observations of reduced diversity or specific alterations in the microbiota of individuals with certain disease states could be thought of as dysbiosis. But an individual with a specific chronic health condition may be simply selecting for a microbiota with reduced diversity, or altered ratios of specific phyla, genera or species. It may even be that someone with a particular disease may benefit from having such an altered microbiota.

The aphorism attributed to Baas Becking – ‘Everything is everywhere, but, the environment selects’ – may be the key concept. Inevitably, each different environment will select a different microbiota. The microbiota then influences the environment, which influences the microbiota, until a stable outcome is achieved. Any external perturbation now has the potential to disrupt this homeostasis. These changes may be subtle or dramatic, they may slow down or reverse disease development, or they may exacerbate or sustain a chronic disease state. We need more evidence of causality before we can even begin to discuss ‘good’ and ‘bad’ members of the microbiota, and we are a long way from identifying an optimal microbiota. This is true for any given individual, never mind the problem of defining what constitutes a good microbiota at a population level. Even if we adopt the concept that the microbiota in a healthy individual is intrinsically healthy, we still cannot know if it is actually driving as yet unseen health defects (cancer, inflammation, neurological diseases?) which will only be obvious over extended time.

There is also the evidence that faecal microbiota transplants (FMT) work well in individuals with Clostridium difficile associated diarrhoea, and promising results are emerging for other health states. This suggests that ‘good’ microbiotas can supplant dysbiotic ones and confer health benefits. But FMT has not been subjected to the kind of rigorous blinded and controlled investigations that more precise interventions would be expected to undergo, and the jury has to remain out for now on whether we can characterise FMT as the replacement of a dysbiotic microbiota with an optimal one.

So, can we talk about ‘good’ and ‘bad’ microbiotas in general terms? Perhaps we can. Resilience to change is almost certainly a feature of a stable microbiome; and if you are healthy, not changing is almost certainly a good thing. Also, the concept of diversity as an asset is not limited to microbiotas, but is an established ecological principle. Of course, we also have to recognise that there will be exceptions to every rule, and that the optimal vaginal microbiota may well be one of low diversity. Nonetheless, we can still have meaningful discussions about increasing diversity and supporting resilience as desirable targets, particularly in complex microbiotas such as that in the gut. But we should be careful of assuming that increasing diversity is always beneficial, because introducing a member of one microbiota to another (and therefore increasing diversity) may have unforeseen consequences. For a ‘real-world’ example, introducing rabbits into the Australian environment increased diversity by one species in the short term, but in the absence of appropriate predators they have caused tremendous damage to a previously stable ecosystem.

We can suggest that where an individual symbiont (such as a healthy human) is in a state of homeostasis and has a stable microbiota, any disruption could present a risk to health. But we don’t need to call this ‘dysbiosis’. We can simply refer to it as ‘changed’, ‘altered’, ‘modulated, ‘disrupted’ or ‘in flux’. So, let’s be careful about speaking of dysbiotic microbiotas. At this point in our understanding we cannot know whether you have a ‘good’ or a ‘bad’ microbiota, but we can say that based on your life to date ‘you have the microbiota you deserve’!

caution sign with picture of antibiotics

Antibiotics: Use with Caution

February 2017. By Karen Scott, PhD, Rowett Institute of Nutrition and Health, University of Aberdeen, Scotland.

Since the discovery of penicillin by Sir Alexander Fleming in 1928, antibiotics have saved millions of lives, and have rightly been described as wonder drugs. Yet since the late 1990s we have become increasingly aware that bacterial resistance to antibiotics is threatening their very use. We can no longer be complacent that we will be able to treat outbreaks of infectious diseases using our existing antibiotic repertoire.

The indiscriminate use of antibiotics in their heyday has led to many bacteria developing resistance to survive. This creates an obvious problem in medicine, where previously treatable diseases become untreatable. The emergence of multi-drug resistant pathogens—methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE) and even multiple drug resistant tuberculosis (MDR-TB)—is the result of this problem. Globalization means that no country can solve this independently; it requires a worldwide initiative. European countries were first to recognise that the widespread use of antibiotics in intensive agriculture, primarily to shorten the time for meat production, was resulting in the spread of resistant bacteria to the human population. In response, the EU banned the use of all antibiotics in farming except to actually cure disease, and certain medically important antibiotics, known as “antibiotics of last resort,” were banned completely. As early as 1969 the SWANN report suggested that the use of medically important antibiotics be restricted in agriculture and this came into practice in 1972 in many European countries. This was followed by a complete ban on the use of antimicrobials as growth promoters, first in Sweden in 1986 and subsequently Europe-wide in 2006. However, China and India have actively used antibiotics as growth promoters since the 1990s, after the European ban. Furthermore, unless procedures are put in place that offer alternatives and monitor compliance, such a ban does not work. Prebiotics are one such alternative in animal husbandry, promoting the growth and activity of the ‘good bacteria’ that are already resident in the animal gut.

Without enforcement, many farms find a way around the rules: in the Netherlands, the amount of antibiotics used did not change between 2006 and 2011, the ‘therapeutic use’ simply increased! There are still many countries around the world where there are no restrictions on the use of antibiotics and bacterial super-pathogens continue to evolve, killing people through treatment failures. Bacteria recognise no borders – travellers frequently return with more than what they intentionally packed in their luggage.

The development and overuse of broad-spectrum antibiotics has created an additional problem. They indiscriminately kill not just the target pathogenic bacterium, but many other bacteria the antibiotic contacts. Pair this with our new awareness that humans are heavily colonised inside and out with diverse bacterial populations performing essential functions to keep us healthy, and the problem becomes apparent. In his book Missing Microbes, Martin Blaser posits that the diversity of our microbial symbionts is declining with each generation. The reduction is so severe that bacterial species that colonised our parents may not be around to colonise our kids. If one of those bacteria performed a unique function, that function would be lost as well. Consider Oxalobacter formigenes, a Gram-negative bacterium that resides in our gut and is capable of degrading oxalate and thus reducing deposition of calcium oxalate, the main component of kidney stones.  The prevalence of O. formigenes in a population ranges from 38% to 62%, with colonization lowest in people susceptible to kidney stones and in people with greater antibiotic exposure, indicating that the bacterium may be particularly sensitive to antibiotics. Are we dooming future generations to ever increasing rates of kidney stones if we eliminate our saviour bacterium from our gut microbiota?

While we are undergoing antibiotic therapy, bacterial diversity within the gastrointestinal tract decreases, although most bacterial species return to detectable numbers once the selective pressure is removed. However, during the time of decreased diversity our resilience to other infections decreases. One very important opportunistic pathogen, Clostridium difficile, has perfected the art of colonising the gut during the at-risk period. C. difficile produces toxins that affect the gut wall, and its infection can develop into a life threatening disease. It is important that we do as much as possible to alleviate the effect that antibiotics have on the commensal microbiota. One approach is using probiotics. There is evidence that consuming probiotics along with antibiotics can prevent C. difficile infection, possibly by creating a temporary bacterial barrier until the normal microbiota recovers. Despite difficulties in comparing scientific studies with different numbers of patients, different ages, and different probiotic strains, the general benefit is outlined in a recent review.

Overall, we need to reduce the use of antibiotics and recent evidence suggests that probiotics can also have a role here. Analysis of data gathered in 12 separate studies showed that routine consumption of probiotics can reduce the number of people developing upper respiratory tract infections (by 11%), reduce the duration of the infection, and importantly reduce the number of antibiotic prescriptions given out for these infections.

Bacteria are very resilient. Faced with extinction due to antibiotic killing, they will try everything to survive. They can acquire resistance genes from neighbouring bacteria lucky enough to contain them. They can even play dead by changing into spores: dormant, non-replicating bacterial forms that cannot be affected by antibiotics, and which can regenerate once the antibiotic pressure is removed. These strategies mean that bacterial antibiotic resistance is here to stay. In order to keep ahead of the game and make sure that antibiotics remain effective in treating infectious disease for our children through to our great-great-great grandchildren, we have to act now, saving antibiotics for situations where they are really needed. It may well be that probiotics and prebiotics will help us to do this.

gut bacteria illustration

Got gas? Blame it on your bacteria

September 2016.

By Prof. Robert Hutkins, PhD –

When I tell friends and family that I study gut bacteria and gut health, the most frequent question I am asked is why some foods cause intestinal gas.   The next question is almost always whether or not gas is such a bad thing.

Bloating, constipation, indigestion, and yes, intestinal gas, are among the most common health complaints among the general population.  Indeed, one of the main reasons for a person to see a gastroenterologist is due to excessive “passing of gas”.

According to the actual research, most healthy people have about 10 to 20 discharges per day.  In terms of volume, this represents about a liter of gas (about a quart’s worth).  And yes, some poor graduate student probably had to somehow measure this.

In general, intestinal gas or flatulence is only a problem in social circumstances, like business meetings, religious events, classrooms, or elevators.  Apart from the sound effects and associated aroma, gas is usually not a serious condition. At minimum it is usually only annoying or embarrassing.  When it’s more severe, however, excessive gas can have considerable impact on quality of life.  It may also be a symptom of a chronic condition, like Irritable Bowel Syndrome (IBS) or celiac disease, for which a physician should be seen.

Although there are many causes for intestinal gas, diet is certainly near the top of the list.  The notion that there are gas-generating foods has become part of our popular culture. On the American Gastroenterological Association list of such foods are milk (for lactose maldigestors only) and high-fiber grains, like whole wheat, oatmeal and oat bran.  Sweeteners like fructose and sorbitol can also be gas-producing.

Unfortunately, many of the healthy foods we are encouraged to eat, including broccoli, cauliflower, cabbage, Brussel sprouts, and other cruciferous vegetables are known to cause gas.  Likewise for onions, leeks, garlic, figs, and prunes.  However, it’s the beans, lentils, and other legumes that are perhaps the most infamous gas-causing foods (thanks, in part, to the campfire scene in Blazing Saddles).

Ultimately, there are two main reasons for intestinal gas.  One is simply swallowed air. Some, but not all, of this air is expelled via burps.

The other source of gas, and the main reason why foods are implicated, is (micro)biological.  Specifically, the foods mentioned above (beans, bran, and broccoli) all contain carbohydrates that resist digestion in the stomach and small intestine and make their way to the colon.  Upon arrival, they become food for the trillions of bacteria that reside there.  These bacteria ferment these carbohydrates and produce gases, mainly hydrogen, carbon dioxide, and methane.  Some gases are adsorbed, some are expelled via breathing, and some are recycled by other bacteria.  But the gas that remains – well, it’s got to go somewhere, and that somewhere is you know where.

It’s important to note that many of these gas-producing bacteria that feed on dietary fibers are often the same species that contribute to intestinal health.  That’s one reason why a little gas can be good, even smelly gases like hydrogen sulfide. It tells you the bacteria in your gut are doing their job.  Indeed, there is a new category of food ingredients called prebiotics that are now being added to yogurt, kefir, crackers, and other foods for the purpose of nourishing gut bacteria.

For people already struggling to get more whole grains, beans, vegetables, and fiber into their diet, intestinal gas can be quite unwelcome.  However, researchers have shown that patience is a virtue.  Consumers who increase their fiber consumption may experience gassiness, but they will often return to normal after a week or two. Gradual increases are often easier to manage. Finally, there is emerging evidence that some probiotic bacteria can reduce the frequency and volume of gas.

Prof. Robert Hutkins, PhD
Khem Shahani Professor of Food Science
University of Nebraska, Lincoln
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