Monday, March 25, 2024

Industrial societies losing healthy gut microbes


Fiber is good for us, but a new study finds that humans are losing the microbes that turn fiber into food for a healthy digestive tract


HEINRICH-HEINE UNIVERSITY DUESSELDORF

Clostridium clariflavum 

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CLOSTRIDIUM CLARIFLAVUM, A FIBER DEGRADING BACTERIUM AT WORK BREAKING DOWN CELLULOSE FIBERS WITH THE HELP OF CELLULOSOMES. PHOTO: ITZHAK MIZRAHI

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CREDIT: ITZHAK MIZRAHI, BEN-GURION UNIVERSITY (BGU)




Everyone knows that fiber is healthy and an important part of our daily diet. But what is fiber and why is it healthy? Fiber is cellulose, the stringy stuff that plants are made of. Leaves, stems, roots, stalks and tree-trunks (wood) are made of cellulose. The purest form of cellulose is the long, white fibers of cotton. Dietary fiber comes from vegetables or whole grain products. Why is fiber healthy? Fiber helps to keep our intestinal flora (scientists call it our gut microbiome) happy and balanced. Fiber serves as the starting point of a natural food chain. It begins with bacteria that can digest cellulose, providing the rest of our microbiome with a balanced diet. But our eating habits in industrialized societies are far removed from those of ancient humans. This is impacting our intestinal flora, it seems, as newly discovered cellulose degrading bacteria are being lost from the human gut microbiome, especially in industrial societies, according to a new report in Science. The study comes from the team of Prof. Itzhak Mizrahi at Ben-Gurion University (BGU) of the Negev in Israel, with support from the Weizmann Institute of Science in Rehovot and international collaborators in the US and Europe.

 “Throughout human evolution, fiber has always been a mainstay of the human diet,” explains lead investigator Sarah Moraïs from BGU, “It is also a main component in the diet of our primate ancestors. Fiber keeps our intestinal flora healthy.” Moraïs and team identified important new members of the human gut microbiome, cellulose-degrading bacteria named Ruminococcus. These bacteria degrade cellulose by producing large and highly specialized extracellular protein complexes called cellulosomes. “It’s no easy task to degrade cellulose, few bacteria can do it.” explains Ed Bayer, from the Weizmann Institute, a world-leader on cellulosomes and coauthor of the study.  “Cellulose is difficult to digest because it is insoluble. Fiber in the gut is like a tree-trunk in a swimming pool, it gets wet but it does not dissolve.”

Cellulosomes are engineered by bacteria to attach to cellulose fibers and peel them apart, like the individual threads in a piece of rope. The cellulosomal enzymes then break down the individual threads of fiber into shorter chains, which become soluble. They can be digested, not only by Ruminococcus, but also by many other members of the gut microbiome. “Bottom line, cellulosomes turn fiber into sugars that feed an entire community, a formidable engineering feat,” says Bayer. The production of cellulosomes puts Ruminococcus at the top of the fiber-degradation cascade that feeds a healthy gut microbiome. But the evolutionary history of Ruminococcus is complicated, and Western culture is taking its toll on our microbiome, as the new study shows.

 “These cellulosome-producing bacteria have been around for a long time, their ancestors are important members of the rumen microbiome in cows and sheep,” explains Prof. Mizrahi from BGU, senior author of the study. The rumen is the special stomach organ of cows, sheep and deer, where the grass they eat (fiber) is converted into useful food by cellulose-degrading microbes, including Ruminococcus. “We were surprised to see that the cellulosome-producing bacteria of humans seem to have switched hosts during evolution, because the strains from humans are more closely related to the strains from livestock than to the strains from our own primate ancestors.” That is, it looks like humans have acquired important components of a healthy gut microbiome from livestock that they domesticated early in human evolution. “It’s a real possibility” says Mizrahi, an expert on rumen biology.

But the story does not end there. Sampling of human cohorts revealed that Ruminococcus strains are indeed robust components of the human gut microbiome among human hunter-gatherer societies and among rural human societies, but that they are sparse or missing in human samples from industrialized societies. “Our ancestors in Africa 200,000 years ago did not pick up lunch from a drive-through, or phone in a home-delivery for dinner,” says William Martin at the Heinrich Heine University Düsseldorf in Germany, evolutionary biologist and coauthor of the study. In Western societies this does, however, happen on a fairly large scale. Diet is changing in industrialized societies,  far removed from the farms where food is produced. This shift away from a fiber-rich diet is a possible explanation for the loss of important cellulose-degrading microbes in our microbiome, the authors conclude.

How can you counteract this evolutionary decline? It might help doing what doctors and dieticians have been saying for decades: Eat more fiber!

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Study finds that for each 10% increase of certain bacteria type in the gut microbiome, the risk of hospitalisation for infections falls by up to a quarter



EUROPEAN SOCIETY OF CLINICAL MICROBIOLOGY AND INFECTIOUS DISEASES



A study of two large European patient cohorts has found that for every 10% increase in butyrate-producing bacteria in a patient’s gut, the risk of hospitalisation for any infection falls by between 14 and 25% across two large national cohorts. The study will be presented at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024) in Barcelona, Spain (27-30 April) and is by Robert Kullberg, Amsterdam University Medical Center, The Netherlands, and colleagues.

Microbiota alterations are common in patients hospitalised for severe infections and preclinical models have shown that anaerobic butyrate-producing gut bacteria protect against systemic infections. These bacteria were investigated because they are commonly depleted in patients hospitalised for severe infections. Second, butyrate may have protective effects in several intestinal diseases (other than infections).

However, the relationship between microbiota disruptions and increased susceptibility to severe infections in humans remains unclear. In this study, the authors investigated the relationship between baseline gut microbiota and the risk of future infection-related hospitalisation in two large population-based cohorts - from the Netherlands (derivation; HELIUS) and Finland (validation; FINRISK 2002).

Gut microbiota were characterised by sequencing the DNA of bacteria to identify the different types of bacteria present in faecal samples of the participants. The authors measured microbiota composition, diversity, and relative abundance of butyrate-producing bacteria. The primary outcome was hospitalisation or mortality due to any infectious disease during 5–7-year follow-up after faecal sample collection, based on national registry data. The authors then examined associations between microbiota and infection-risk using computer modelling. Further statistical  modelling was used to adjust for variables including demographics, lifestyle, antibiotic exposure, and comorbidities.

The researchers profiled gut microbiota from 10699 participants (4248 from The Netherlands and 6451 from Finland. A total of 602 participants (The Netherlands: n=152; Finland: n=450) were hospitalised or died due to infections (mainly community-acquired pneumonia) during follow-up.

Gut microbiota composition of these hospitalised/deceased participants differed from those without hospitalisation for infections. Specifically, each 10% higher abundance of butyrate-producing bacteria was associated with a reduced risk of hospitalisation for infections – 25% lower for participants from the Dutch cohort and 14% lower for the Finnish cohort. All types of infections were assessed together, not any one in particular. These associations remained unchanged following adjustment for demographics, lifestyle, antibiotic exposure, and comorbidities.

The authors say: “Gut microbiome composition, specifically colonisation with butyrate-producing bacteria, is associated with protection against hospitalisation for infectious diseases in the general population across two independent European cohorts. Further studies should investigate whether modulation of the microbiome can reduce the risk of severe infections.”

The authors say further analysis will be needed before trails in patients can begin. One of the challenges is the face are the butyrate-producing bacteria are strictly anaerobic (meaning they respire without using oxygen and cannot tolerate oxygen), which makes it very difficult to transport viable bacteria into the gut. Several research groups are working on addressing these challenges.

This press release is based on abstract CS0502 at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). The material has been peer reviewed by the congress selection committee. It is about to be submitted to a medical journal for publication. The full paper is not yet available but the authors are happy to answer your questions.

For full abstract click here


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