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Probiotics in fridge

Designing Probiotic Clinical Trials: What Placebo Should I Use?

By Daniel J. Merenstein, MD, Professor, Department of Family Medicine and Director of Research Programs, Georgetown University Medical Center, Washington DC

Specifying a placebo is one of the most important decisions for a clinical trialist. The first trial I led was a study giving Benadryl to kids to see if it helped them sleep. We spent hours working with our pharmacist on the placebo to make sure it had the same sweet cherry taste of the active drug, Benadryl. We didn’t want parents to be able to determine whether they were randomized to Benadryl or the placebo by comparing the study product to what they had at home. Do study subjects really do this? Yes. Early in my career I was helping an orthopedist who was putting pain pumps directly into a patient’s ankle post-surgery in order to see if it would decrease oral narcotic usage. One of our first patients pulled his pump out, tasted the medicine and called us late at night complaining he was in the saline (placebo) group.

When undertaking a study on probiotics, and specifically probiotic yogurts, we can debate for weeks about the best placebo. Our intervention is yogurt fortified with an additional probiotic. Therefore, our intervention yogurt contains both the starter lactic acid bacteria and the probiotic. So assuming we want both groups to get nutritionally equivalent yogurt that can be blinded our placebo options could be as follows. Note that in recent years, we have become more cognizant that dead microbes may not be biologically inactive.

Placebo Microbiological content of Placebo Research question addressed
Yogurt Live starter cultures, no probiotic What is the contribution of probiotics to any health benefit?
Acidified yogurt No live or dead microbes What is the contribution of live probiotic + live starter cultures to any health benefit?
Heat treated yogurt No live microbes, dead starter microbes Beyond any contribution of dead starter cultures, what is the contribution of live probiotic + live starter cultures to the health benefit?
Heat treated probiotic yogurt No live microbes, dead starter + dead probiotic microbes Beyond any contribution of dead probiotics + dead starter cultures, what is the contribution of live probiotic + live starter cultures to the health benefit?
Probiotic yogurt using a different probiotic Live starter cultures, live probiotic different from the probiotic in the intervention What is the contribution of the intervention probiotic to any health benefit compared to the control probiotic?

 

We chose regular yogurt (the first option above) and now about eight papers later, I would say that about 50% of reviewers question our choice.

There are many reasons the placebo needs to be well considered, including the specific research question under consideration. But an important one is clinical equipoise, “a state of genuine uncertainty on the part of the clinical investigator regarding the comparative therapeutic merits of each arm in a trial”, as defined Freedman 1987. Thus, for example in a study of a new hypertension drug, one cannot use a placebo that has no chance of lowering a patient’s blood pressure as a comparator as that is ethically indefensible. Instead, a well proven hypertension drug will be studied versus the new experimental drug.

For most of my career the goal in my studies was to pick a placebo that was as inactive as possible that still smelled, looked and tasted like my active intervention. However, the times are changing. When I started working there were fewer than 200 randomized controlled clinical probiotic trials retrievable from PubMed; today the number is over 2,300. Well that means we have gone beyond merely recognizing the value of probiotics in different indications, to detailed comparisons of different probiotic and non-probiotic interventions, so one has to consider how inactive their placebo is for probiotic intervention trials.

In 2020 the American Gastrointestinal Association came out with recommendations and guidelines after they conducted a thorough review of probiotic evidence. (See ISAPP blog ISAPP take-home points from American Gastroenterological Association guidelines on probiotic use for gastrointestinal disorders.) For three indications, they recommended using select probiotics over no or other probiotics, in populations of preterm low birthweight infants, patients receiving antibiotics, and patients with pouchitis. So what does this mean for trials evaluating one of these indications? It means that the placebo should be an active control, a probiotic versus probiotic trial.

Today if I’m asked what placebo should be used, my first question is what indication are you studying? If you are studying infant colic or preterm low birthweight infants, I think you need an active control, such as another probiotic. (Colleagues and I suggested this for probiotic studies on necrotizing enterocolitis in 2013.) If you are studying anxiety, then an inert placebo makes the most sense since insufficient evidence exists for any probiotic for this endpoint as yet. In the case of antibiotic associated diarrhea, it will be a much longer discussion as the data are not clear, but it would be reasonable for an IRB to argue that your placebo should be another probiotic. It is not ethical to deny a placebo group an effective intervention if one is available.

So in the last 15 years of my career the answer to what placebo should I use has greatly changed. As probiotic research has advanced, so has the evidence base for usage. As we proceed with research we now need to consider conducting our clinical trials differently. This is just another example of how probiotic evidence has matured over a relatively short period of time.

Can fermented or probiotic foods with added sugars be part of a healthy diet?

By Dr. Chris Cifelli, Vice President of Nutrition Research, National Dairy Council, Rosemont IL, USA

What about added sugar in fermented or probiotic foods? I am almost always asked this question whenever I give a nutrition presentation, no matter the audience. It’s not a surprising question as people care about what they eat and, often, are looking for ways to reduce their intake of sugar. Yet, if someone wants to add fermented or probiotic foods such as yogurt, kefir or kombucha to their diet, they often find the products available to them contain sugar as an added ingredient.

Should these products be part of you and your family’s healthy eating plan even if they have added sugar? The simple answer – yes, they likely can still fit into a healthy eating plan.

According to the U.S. Food and Drug Administration, ‘added sugars’ are defined as sugars that are either added during the processing of foods or are packaged separately as sugars (e.g. the bag of sugar you buy to make your treats). Added sugars in the diet have received attention because of their link to obesity and chronic disease risk. The World Health Organization, American Heart Association, Dietary Guidelines for America, and American Diabetes Association all recommend reducing added sugar intake to improve overall health. While data from the US National Health and Nutrition Examination Survey (NHANES) has shown that consumption of added sugar decreased from the 2007-2010 to the 2013-2017 surveys, the most recent Dietary Guidelines Advisory Committee report noted that the mean usual consumption of added sugars was still 13% of daily energy in 2015-16, which exceeds recommendations of 10%.

Including fermented foods in one’s diet may be important for overall health. The recent ISAPP consensus paper on fermented foods indicated that fermented foods, especially the live microbes contained in them, could benefit health in numerous ways, such as by beneficially modulating the gut microbiota or the immune system. Similarly, foods with added probiotics may confer health benefits ranging from impacting digestive health to metabolic parameters, depending on the probiotic contained in the product. Our understanding of the gut microbiota continues to evolve, but one thing is for certain: it is important for health. This provides a compelling reason to find ways to include these foods in healthy eating patterns.

So, back to the question at hand. Should you reduce or eliminate fermented foods and foods with probiotics from your diet if they have added sugars? Just like a “spoonful of sugar helps the medicine go down,” a little added sugar to improve the palatability of nutrient-dense foods is okay. Indeed, government and health organizations all agree that people can eat some sugar within the daily recommendations (which is 10% of total daily calories), especially in foods like yogurt or whole-grain cereals, or other healthy foods. And, there is no scientific evidence to show that the sugar in these products reduces the health benefits associated with eating foods like yogurt or probiotics. Human studies assessing health benefits of probiotic foods typically use products with added sugar, yet health effects are still observed.

The next time you are out shopping you can choose your favorite fermented or probiotic-containing food guilt free, as long as you’re watching your overall daily intake of sugar. But, if are you are still concerned, then choose plain varieties to control your own level of sweetness or you could opt for a probiotic supplement to avoid the sugar. Whether you go with the sweetened or unsweetened version of your favorite fermented food, you’ll not only get the benefit of the live microbes in these products but also the nutritional benefit that comes with foods like yogurt.

 

Ambient yogurts make a global impact

By Prof. Bob Hutkins, PhD, University of Nebraska Lincoln, USA

Quick, which country consumes the most yogurt? Must be France? Or the Netherlands? Maybe Turkey? The United States, perhaps? Try none of the above: the answer is China.

While many other countries consume way more yogurt than China on a per capita basis, China’s population gives it an advantage, with 1.4 billion potential consumers. And yogurt has become one of the most popular snack foods in China. It’s especially trendy among young and affluent urbanites. Indeed, total consumption of yogurt in China now exceeds that of France, the Netherlands, Turkey, and the United States, combined!

Whereas per capita consumption of yogurt in China in 2000 was around 1 kg per person per year, it’s now approaching 5 kg. Yogurt consumption even exceeds that of fluid milk.

Considering that dairy consumption was virtually non-existent in China for thousands of years, this trend is nothing short of a cultural phenomenon. While some of the yogurt consumed in the country is produced by domestic manufacturers, yogurt and yogurt ingredients are also being imported from other countries in the region, including New Zealand and Australia.

There is, however, one major difference between yogurt typically consumed in China and the products consumed in other regions. Indeed, ambient yogurt, short for “yogurt-based product for ambient distribution”, is all the rage in China.

Ambient yogurt and yogurt drink products, as the name implies, are stable at room temperature. This is achieved by heat-treating the yogurt after fermentation.  Many ambient yogurts are aseptically processed similar to ultra-high-temperature processed (UHT) products, leaving the product commercially sterile (i.e. without live microbes) and stable for up to a year. In China, these products can still be labeled as yogurt.

Not only are these ambient yogurt products convenient for retailers, but also, a cold-chain infrastructure, often absent in rural areas of China, is not necessary during transport and distribution. Perhaps for this reason, ambient yogurts are also being introduced in other regions, including Africa, South America, and the Middle East.

The popularity of yogurt in China, in the absence of a live microbe label declaration, is evidently due to the ‘healthy’ virtues or halo effect ascribed to yogurt, because of its high protein, calcium, and vitamin content. Perhaps there are also postbiotic benefits in the yogurt – this would be an interesting topic for research. But the novel flavors, textures and grab-and-go convenience, especially for drinkable yogurt products, also appeals to teens and young adults.

Traditionalists balk at the very idea of heat-treating yogurt and inactivating the live microorganisms. In some countries, such products cannot even be labeled as yogurt. In the U.S., these products can be labeled as yogurt but must be further labeled as “heat-treated”.

In reality, consumers’ expectation of live microbes in yogurt is so ingrained that heat-treated yogurts are nearly impossible to find in the United States. Indeed, yogurt, kefir, and other cultured milk and non-dairy products are promoted, in part, on the high number of viable microbes they contain. Probiotics are added to more than 90% of the yogurts sold in the United States.

According to international CODEX standards, yogurt must be made with Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus, AND must contain at least 107 CFU/g “through to the date of minimum durability after the product has been stored under the storage conditions specified in the labeling”. Any other labeled bacteria must be present at a minimum of 106 CFU/g. The CODEX standards have been widely adopted, although some countries have lower minimum levels.

Interestingly, and despite appeals by yogurt manufacturers, the U.S. Food and Drug Administration does not require minimum numbers of CFUs for yogurt. They have been considering changes that would be consistent with CODEX for more than a decade. In regions that do not require the CODEX standards, the International Dairy Foods Association offers the Live & Active Cultures (LAC) seal, which requires 107 CFU/g of yogurt cultures at time of manufacture.

The China National Food Safety Standard for Fermented Foods does specify a minimum Lactobacillus count of 106 CFU/g, but importantly, also includes the following footnote:

“products that have gone through heat treatment after the fermentation process will not be subjected to any requirements on the minimum Lactobacillus Count”

Such products, however, must be labeled as heat-treated. It should be noted that there is still a substantial market for more traditional (chilled) yogurt containing live microorganisms.  Still, ambient yogurts account for most of the yogurt consumed in China.

Given the relatively flat yogurt market in Europe and the United States, it should not be surprising that this rapidly growing market in China has attracted so much attention.  The China Nutrition Society and government policymakers have recommended that consumers increase dairy consumption to 3 times higher than current levels. That means a lot more yogurt will be consumed in China.

Translated, that means, from culture companies to processing and packaging industries, there will continue to be plenty of interest, innovation, and investment in yogurt for the Chinese population. For example, new generation yogurt products have recently been introduced with the claim of having 90 days’ shelf-life and containing live probiotic bacteria.

Still, whether by new or traditional technologies, the availability and consumption of live microbes in yogurt and other cultured products may be expected to increase as Chinese consumers become more informed about their health benefits. Perhaps, as cold-chain infrastructure also improves, these live yogurts may become a bigger part of the yogurt culture in China.

 

Locally produced probiotic yogurt for better nutrition and health in Uganda

By Prof. Seppo Salminen, Director of Functional Foods Forum, University of Turku, Turku, Finland

Can locally produced probiotic yogurt be a way to increase the health and wealth of people in resource-poor areas of Uganda? Recently Dr. Nieke Westerik, a researcher from the Netherlands, partnered with a local Ugandan team to explore a yogurt production and distribution program similar to one that had previously proved successful in low-income areas of Argentina.

Since 2008, “Yogurito Social Program” has been operating in Argentina and now some 350,000 schoolchildren in less developed provinces enjoy the benefits of daily probiotic yogurt developed locally. Dr. Westerik (Free University of Amsterdam and Yoba 4 Life Foundation), with support from former ISAPP board member Prof. Gregor Reid, has now helped adapt the program to local needs in Uganda, making use of a well-known probiotic (Lacticaseibacillus rhamnosus GG) plus a yogurt starter (produced by the Yoba 4 Life Foundation) for production of the yogurt. The probiotic’s health effects have been demonstrated in human intervention studies.

The team worked on technical training and quality control of the locally produced yogurt, developing a production protocol suitable for Ugandan small-scale manufacture of probiotic fermented foods. Dr. Westerik’s team then conducted two clinical studies that demonstrated that the consumption of this probiotic product improved natural defenses and prevented respiratory infections (e.g. the common cold) and intestinal infections, which are the infectious conditions of greatest relevance in childhood in Uganda.

Yogurt is a new tool for individuals in developing areas of Uganda to achieve better health through diet, with potentially significant social and economic implications. Both the Ugandan and Argentinian experiences illustrate the power of microbes to positively impact the lives of women, men, and children. Given the positive results from these two different contexts, such activities could be replicated in other geographical areas—with either dairy, vegetable, or grain fermentations used locally with defined, well-studied starter cultures.

Further reading:

Julio Villena, Susana Salva, Martha Núñez, Josefina Corzo, René Tolaba, Julio Faedda, Graciela Font and Susana Alvarez. Probiotics for Everyone! The Novel Immunobiotic Lactobacillus rhamnosus CRL1505 and the Beginning of Social Probiotic Programs in Argentina. International Journal of Biotechnology for Wellness Industries, 2012, 1, 189-198.

Westerik N. 2020. Locally produce probiotic yoghurt for better nutrition and increased incomes in Uganda. PhD thesis, Free University of Amsterdam, The Netherlands.

Reid G, Kort R, Alvarez S, Bourdet- Sicard R, Benoit V, Cunningham M,  Saulnier DM, van Hylckama  Vlieg JET, Verstraelen H, Sybesma W.  Expanding the reach of probiotics through social enterprises. Beneficial Microbes, 9 (5): 707-715.

YOGURITO –the Argentinian social program with a special yogurt

 

 

 

Bulgarian yogurt: An old tradition, alive and well

By Mariya Petrova, PhD, Microbiome insights and Probiotics Consultancy, Karlovo, Bulgaria

Family and family traditions are very important to me. Some of you may have seen my previous blog post on fermented food and my father’s tradition of making fermented cabbage and vegetables every autumn. Of course, this is not limited to my family – in Bulgaria, it is our culture and our country’s tradition. But despite the fact that I wrote about fermented vegetables first, Bulgarians are much more proud of another fermented product – yogurt.

I still remember waking up every morning when I was a kid and having a healthy homemade yogurt to start the day. I still do when I am back at home, because my father continues to make yogurt at home. Here, I’ll take you on a new adventure and tell you all about Bulgarian yogurt, an old tradition still alive in every home.

Élie Metchnikoff and his work are well familiar to anyone involved in probiotic research. In short, Metchnikoff observed in 1907 that Bulgarian peasants lived longer lives and he attributed this to their daily consumption of yogurt.

Thanks to Metchnikoff, research on Bulgaria and Bulgarian yogurt was put on the map because of our healthy way of living and eating fermented foods. You may know this part of the story. Still, few actually know that Metchnikoff was intrigued by the work of the Bulgarian researcher Stamen Grigorov a few years earlier. In fact, it was because of Stamen Grigorov’s work that we now know ‘who’ (i.e. which microbes) live in our yogurt and how essential those tiny bacteria are. In 1905 Stamen Grigorov actually discovered and isolated for the first time Lactobacillus bulgaricus (now known as Lactobacillus delbrueckii subsp. bulgaricus) from homemade yogurt. That’s why we are so proud of Bulgarian yogurt. Not only do we love to eat it, but the probiotic research was partially initiated in our country, and an entire Lactobacillus species is named after our country. There is even a small museum dedicated to Bulgarian yogurt and to the work of Stamen Grigorov, located in the house where he was born. In the museum, if you are visiting Bulgaria, you can learn how to make yogurt at home and a bit more about the history of Grigorov’s discoveries.

We are so proud of our yogurt that many Bulgarians will tell you that ancient Bulgarian tribes were the ones who discovered yogurt by accident. Since Bulgarian tribes were nomadic, they carried the milk in animal skins, which created an environment for bacteria to grow and produce yogurt. This is indeed the way people learned to make yogurt, but it most likely happened in many places independently. Of course, I know many countries make yogurt but I remain proud of all the discoveries that happened in my country (I am saying this because at times I have been judged when I tried to say how important we find the yogurt in Bulgaria and how proud we are).

Yogurt is a tradition in Bulgaria. I don’t know a Bulgarian who does not eat yogurt on a daily basis, up to a few pots per day. And I am not talking about those sweet yogurt products that are made by adding jam or vanilla. I am talking about real, natural yogurt, slightly sourer than most of the products that can be found in the Western world. We add yogurt to almost everything, it is just the perfect addition. It is even the basis of a traditional Bulgarian cold summer soup called “tarator,” made of yogurt, water, cucumber, garlic, and dill. We also make a salad with it called “snezhanka”, and it contains yogurt, cucumbers, garlic, and walnuts. (Recipes can be found below if you want to try something new during the lockdown.) In fact, I am so “addicted” to our yogurt that in every country I go to, the first thing I have do is to find a good yogurt. It took me years to find a good one in Belgium when I lived there (even though one product was labelled ‘Bulgarian yogurt’, it was not the same for sure). In Canada, it was somehow easier. After trying a few different products, it was even faster to find something that I like in the Netherlands, but they have many kinds of milk products. Yet none of them are truly comparable with what you can find in Bulgarian shops. Even the smallest shops have at least 3 to 4 different types because we have a lot of yogurt factories. Every product is different, it has a unique taste and can be made of different kinds of milk.

But honestly, nothing is the same as the homemade yogurt. Many people still make yogurt at home, including my father. I don’t quite remember a time when there was no homemade yogurt on the table at home. It was initially my grandmother making the yogurt and the white Bulgarian cheese (it is nothing to do with Feta but that’s the closest way to explain what it is). So it was somehow logical that my father started making yogurt as well. He knows the technique from his grandmother and grew up with fresh homemade yogurt. My grandparents had a lot of cows, sheep, and goats, so we always had plenty of milk to ferment. Making yogurt at home is so very simple that more and more young people dare to do it. In fact, making yogurt is so easy, I wonder why I am not doing it myself during the lockdown.

How to make it, you may ask?

So you need fresh milk, which my family in Bulgaria currently gets from a local farm. The milk is carefully boiled, and while it is still warm, transferred to a preferable container where you want to make the yogurt. We use old yogurt jars that were very popular before. For some time, my father also used Tupperware, so you can choose anything that you find handy. Before transferring the milk, my father also separates the cream from the milk in a separate jar and uses it to make homemade butter by constantly shaking the jar for around 10 minutes (it is an intensive workout, I tried it a few times!). The biggest problem these days is having a good starter culture so you can begin the milk fermentation. As a starter culture, most of the people, including my father, use a spoon or two of the previous batch of yogurt. So my father never finishes all the yogurt; he always makes sure that there are some leftovers so he can start a new fermentation. He usually adds one tablespoon of the old yogurt to 500 ml warm milk (around 45 C). Of course if the milk is too hot, the bacteria present in the starter culture will die, and nothing will happen. There is also the case that the milk is too cold, and then it will most likely still ferment, but it will have a strange consistency, something between milk and yogurt. If my father is out of old yogurt to start a new fermentation, he usually buys his favorite yogurt from the shop and uses this as starter. Once the jars are filled, he packs blankets all around them to keep the environment warm so the fermentation will begin. From here, you need around 4h to 5h to have a nice homemade yogurt. Simple and straightforward. The next morning you can have a great family breakfast, remembering the old traditions, talking about old memories, passing on the torch to the new generation, and enjoying a healthy start to the day.

The next time you have yogurt, I hope you enjoy it and remember the Bulgarian traditions!

 

Tarator soup recipe:

What you need: 1 cucumber, 250 -300 g yogurt, 1-2 cloves crushed garlic, salt, oil, water, fresh chopped dill. (Most of the ingredients depend on your taste so feel free to add more or less of certain ingredients. Some people also add parsley and walnuts, but it is up to your taste.)

How to make it: Peel and cut the cucumbers into cubes and put them in a preferred bowl; add the crushed garlic, and the minced dill. Beat the yogurt until it turns to liquid and mix it with the rest of the ingredients. Add salt and oil to taste. Add water to make the soup as liquid as you like. Put into the refrigerator to cool it. You can also make it with cold yogurt and cold water. It is perfect for the hot summer days.

Snezhanka (which means “Snow White” in Bulgarian) salad recipe:

What you need: 1 cucumber, 500 g yogurt, 1-2 cloves crushed garlic, 2-3 spoons ground walnuts, salt, oil, fresh chopped dill. (Again, it depends on your taste, if you like more cucumber or yogurt just add more.)

How to make it: First strain the yogurt for a couple of hours, so that all unnecessary water is drained away. Peel and cut the cucumbers into cubes and put them in the bowl. Add the strained yogurt. Add the fresh dill, salt and oil to taste. Sprinkle the walnuts on top of the salad. Perfect for all seasons. If you don’t have a fresh cucumber, you can also use pickles — the final result is also very delicious.

ISAPP RELEASES NEW INFOGRAPHIC: “PROBIOTICS: DISPELLING MYTHS”

How often do you hear information about probiotics that is just plain wrong? Too often write-ups on probiotics in blogs, websites, articles written by the lay press, and even sometimes in scientific journals is not true to the science. The latest ISAPP infographic corrects several common misconceptions about probiotic dose, sweetened probiotic yogurts, fermented foods, and more. In doing so, this infographic furthers ISAPP’s core values of stewardship, advancing the science and education.

This resource was developed by ISAPP’s Science Translation Committee and approved by  the ISAPP board of directors.

salminen and hutkins at YINI

Fermented Foods in Nutrition & Health

November 2017. Discussed at International Union of Nutritional Sciences (IUNS) Congress session. By Prof. Seppo Salminen, Director of the Functional Foods Forum, University of Turku.

Recently, the Yogurt in Nutrition Initiative (YINI) convened a scientific session as part of the International Union of Nutritional Sciences (IUNS) Congress, held in Buenos Aires from October 22-27, 2017. The session focused on how yogurt and other fermented foods affect the composition and activity of the gut microbiota and health. Lectures covered microbiota development in humans, metabolic effects of yogurt and fermented foods, the role of fermented dairy foods on health, and the role of yogurt and fermented foods in nutritional guidelines

Professor Robert Hutkins and I presented at the YINI session. Dr. Hutkins spoke about “Health benefits of fermented dairy foods: microbiota and beyond” and started by defining the role of microorganisms during food fermentations. He then reviewed current research findings on the impact of fermented foods on the human intestinal microbiota. He also distinguished between the microbes that perform the fermentation and those added specifically as probiotics. Although they are often closely related, they are not the same. Both culture-based and molecular methods have shown that although microbes consumed in fermented foods often survive transit, they rarely persist after consumption has ended. Still, they may be able to modulate functional activity in the gut and, in the case of yogurt bacteria, improve tolerance to lactose.

My presentation was titled “Improving your diet with fermented foods: harmonizing dietary guidelines including fermented milks” and I reviewed the role of yogurt in dietary guidelines and recommendations in different countries along with the regulatory status of yogurt and health claims. The talk focused on existing guidelines in Europe; specifically, the live bacteria in yogurt and lactose intolerance claim approved by the European Food Safety Authority. This claim states that yogurt cultures improve lactose digestion (and tolerance) in individuals with lactose maldigestion. Additionally, I suggested that fermented dairy products should be included in dietary guidelines in a more consistent manner, as recommendations currently vary from country to country. A special focus was also given to an Argentinian social program which provides at present over 200,000 school children with locally produced yogurt with a probiotic to improve their health and well-being.

The role of fermented foods and especially yogurt has gained substantial attention among researchers, clinicians, public health workers, and consumers. In addition to the live organisms present in fermented foods, peptides and other metabolites produced by these organisms may also mediate important health benefits. Thus, cultured dairy foods and other fermented products may have important effects on public health and their consumption should be encouraged.