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Episode 38: Microbes that break down mucus and milk to benefit the host, with Dr. Clara Belzer PhD

/in Podcast, Season Three /by Laura

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We discuss microbes, mucus, and milk with Dr. Clara Belzer PhD from Wageningen University in the Netherlands in this episode. Dr. Belzer, a molecular geneticist, specializes in studying the microorganisms that are equipped to break down the glycans in mucus and human milk within the host environment.

Key topics from this episode:

  • Dr. Belzer’s research focuses on the microbes living in the host that survive on glycans (chains of sugars) produced by the host: milk oligosaccharides and mucus. The host is not good at digesting these sugars, but can use them when they’re separated into smaller components. These long chains of sugars end up in the large intestine, where certain microbes begin to digest them.
  • There seems to be an evolutionary adaptation that sustains the symbiotic relationship between human milk and bacteria in the infant gut; many immune molecules in the human milk suppress pathogens, so the human milk oligosaccharides (HMOs) are available to the bacteria in the infant gut that can break them down. The bacteria are not suppressed by the acidic environment in the infant gut.
  • Human milk is the best food for infants, but innovations in infant formula may make it more similar to human milk.
  • Akkermansia is a genus of bacteria mostly found in adults, but also sometimes in infants, which grows in the mucosal layer of the intestines. (It doesn’t survive on dietary glycans.) Dr. Belzer’s hypothesis is that the environment created by human milk in the infant gut also fosters bacteria that can grow on mucus, creating a succession of host-benefitting bacteria. They found that HMOs, in addition to mucus, can support the growth and survival of Akkermansia, potentially helping it build a microbial network.
  • There’s a genetic component to the HMOs contained in human milk; similarly, the sugar content in the mucosal glycans is related to host genetics.
  • Lean individuals have a higher abundance of Akkermansia; these bacteria improve metabolism (for example, increasing insulin sensitivity) and have effects on the immune system, which both contribute to a lean phenotype. The root of these effects may be the strengthening of the gut barrier, which dampens signals from the lumen.
  • Dr. Belzer has used both omics and culture-based approaches in her research. As part of her research she tries to make microbial synthetic communities, growing them in the lab and stimulating them with different glycans. This technique yields insights about the functions and microbial ecology in the gut.
  • Killed Akkermansia are still able to bring health benefits to the host. Dr. Belzer had the idea that the pili structures on the bacteria were what communicated with the host, and sure enough, this was borne out in a study that showed the proteins in the pili (Amuc_1100) remained intact in the pasteurized bacteria and could stimulate the host immune system. This is a valuable finding because Akkermansia are difficult to culture.
  • When Akkermansia fails to occupy the niche in the mucus layer, Bacteroides species may occupy the niche instead, forming a different microbial community in the mucus. Research is ongoing about the effects of different microbes carrying out similar functions for the host. Furthermore, scientists have many more microbial functions to discover.

Episode abbreviations and links:

About Dr. Clara Belzer PhD:

Dr. Clara Belzer is Associate Professor Microbiology at the Laboratory of Microbiology of Wageningen University. The Belzer group is called ‘Microbes Mucus and Milk’ and the research is focused on the interaction of the gut microbiome with host mucus and milk. After obtaining her PhD at the Erasmus Medical Center Dr. Belzer did a postdoc at Harvard medical school. By now Dr. Belzer has years of experience on gut microbiome studies on anaerobes, including synthetic communities and different biotic concepts, with a special interest for the Akkermansia muciniphila. The group of Dr. Belzer works on several microbiome HMO and mucus related topics funded by national and international grants, some also in collaboration with medical centers and industry.

Pasteurized Akkermansia muciniphila as a postbiotic: EFSA approval and beyond

/in ISAPP Science Blog /by KC

By Prof. Seppo Salminen, University of Turku, Finland

Earlier this year, the European Food Safety Authority (EFSA) delivered an opinion that heat-treated Akkermansia muciniphila is safe for use as a novel food in the European Union. EFSA described A. muciniphila as a “well‐characterised non‐toxin producing, avirulent microorganism that has been reported as part of normal gut microbiota” and determined based on a literature review that its safety is adequate for use as a food supplement or in foods for special medical purposes, at a specified maximum dose.

ISAPP connected with three individuals from A-Mansia Biotech, the company that initiated the EFSA request: Prof. Willem M. de Vos and Prof. Patrice D. Cani, as well as the company CEO Michael Oredsson. They jointly answered some questions on their EFSA success and plans for the future.

Originally, what led you to test whether the pasteurized form of the live microbe might be able to confer a health benefit?

We first noticed that killing Akkermansia by using autoclaving (121°C 20°C) completely abolished the beneficial effects of Akkermansia. However, we wanted to test whether a milder procedure (i.e. pasteurization) could keep some structures of the outer membrane of Akkermansia intact and therefore still able to interact with the host. We knew that several other classical probiotics (types of lactobacilli) partly retained their effects after pasteurization. Our surprise was to see that pasteurization successfully maintained the effects of Akkermansia compared to the live form, but even increased its efficacy.

Pasteurised Akkermansia has now been extensively studied for safety and health effects. Does this make it the first real postbiotic, as defined by ISAPP?

If we are accepting the ISAPP definition proposed in 2021, we can answer yes to this question. Prof. Cani in his scientific capacity believes indeed that the product (pasteurized Akkermansia) is unique and can fall under this definition. Whether A-Mansia will be positioning the pasteurized Akkermansia as a postbiotic according to that definition is still to be discussed.

Pasteurised Akkermansia has been demonstrated to control gut barrier and reduce inflammation associated with fat storage and obesity – will we see a product that helps in weight loss/control?

Akkermansia is clearly playing a major role by tackling the gut barrier dysfunction which is the root cause of the different metabolic problems mentioned here (i.e., inflammation, fat storage, liver/fat tissue inflammation) and they are all connected to better energy expenditure/oxidation when a lower inflammation/insulin resistance is observed. Therefore, pasteurized Akkermansia should help to maintain a healthy weight and abdominal fat. A product focusing on a better weight management is currently under development at A-Mansia.

Is the next step to apply for an EU health claim?

All the current human investigations and studies at our company are aiming at fulfilling future EU health claims.

It took two years to get the acceptance for the safety of inanimate pasteurised Akkermansia – what do you think of this timeframe for safety assessment?

This is perfectly in line with what the EFSA was expecting, although it was a few months delayed with the COVID-19 crisis. The assessment was very clear, smooth and well managed by the EFSA.

In general, what do you think the future holds for postbiotics as food ingredients?

We are entering into a new era, first with next-generation beneficial bacteria, and Akkermansia as one of the most studied (if not the most studied). The pasteurized form is so active, stable, and easy to use that the postbiotic era, as led by this example, is a novel and innovative manner of targeting the microbiome for improving/maintaining health.

 

As the science on health benefits for similar postbiotic substances continues to advance, we may see more ingredients qualifying as true postbiotics. More products are likely to follow a similar path, considering the practical advantages of delivering non-living substances to consumers.