Gut bacteria need food to survive, but new research suggests that what happens when they do not get enough of the right food can be more serious than simply disturbing digestion. Researchers have found that when dietary fibre and certain plant proteins are in short supply, some gut microbes can start breaking down the mucus lining that protects the intestines.The findings come from two studies led by Jenna AbuSalim and Joshua Rabinowitz of Ludwig Princeton. One was published in the Proceedings of the National Academy of Sciences, while the other appeared in Nature Metabolism. Together, the studies provide new clues about how diet changes the activity of gut bacteria and where some important compounds in the body actually come from.What happens when gut bacteria run low on fibreThe intestine has a protective mucus layer that helps keep trillions of bacteria away from the cells of the gut wall. The researchers found that when bacteria have less plant material available, they can turn to proteins from the host, including proteins present in this mucus layer.Using stable isotope-labelled proteins in mice, the team was able to track where different metabolites came from. The results showed that harmful phenols were largely produced when bacteria consumed host proteins, including those from the intestinal mucus.These included p-cresol sulfate and phenol sulfate, compounds that have been associated with systemic toxicity in people with kidney disease and poorer outcomes among cancer patients.Fibre gives the microbes another food sourceThe study also found that fibre could reduce this bacterial breakdown of the gut lining. But fibre was not the only dietary component that mattered.The researchers identified a group of indigestible plant proteins that reach the gut and can be used by microbes. They called them “proteins imitating fiber”, or Prif. These proteins helped push bacterial metabolism towards phenylpropionate and hippuric acid, metabolites associated with gut health and healthy body weight.“Our studies showed that both the fiber and indigestible proteins from plants—which we call ‘proteins imitating fiber,’ or Prif—shift the balance of phenol metabolites from the harmful kind made from tyrosine to the healthful variety derived from phenylalanine,” said AbuSalim.The researchers believe Prif could become an important part of how scientists think about dietary fibre and gut health.“We think Prifs represent an emerging class of dietary nutrients that shape the composition of the gut microbiome and could have a far-reaching influence on metabolic health,” said AbuSalim.Not every gut metabolite comes from bacteriaThe second study brought another surprise. Scientists have often assumed that many phenol and indole metabolites found in the body are made mainly, or only, by gut bacteria.However, experiments involving mice, rats and human cells showed that mammalian cells can also produce many of these compounds. Some remained at substantial levels even after antibiotics disrupted the gut microbiome, while metabolites made exclusively by bacteria fell.The finding could matter for future probiotic and diet-based treatments because changing gut bacteria may not always change the level of a particular metabolite.“There’s growing interest across medical disciplines in manipulating the human microbiome or using its metabolic products themselves for therapy,” said Rabinowitz. “Diet holds great promise for controlling the microbiome and its outputs. But to devise effective therapeutic interventions, we need to understand what aspects of the diet control which microbial outputs.”The researchers said the combined findings could eventually help doctors and nutritionists give more specific advice about which foods may influence particular microbial products.
