Dietary fibre helps ‘good’ bacteria win battle of the microbiome

Dietary fibre helps ‘good’ bacteria win battle of the microbiome

Feeding beneficial gut bacteria with fibre appears to help a signalling mechanism which limits the growth of harmful pathogens, according to a new study published in Science.

Dietary fibre produces the short-chain fatty acid (SCFA) butyrate, which signals to cells lining the gut wall to maximise oxygen consumption. When the number of butyrate-producing microbes was depleted through use of antibiotics, the level of signalling was reduced, discovered the scientists from the University of California at Davis (UC Davis).

Adequate signalling is necessary to limit the availability of free oxygen within the open space (known as the lumen) in the gut. This in turn restricts the number of harmful bacteria such as Escherichia coli and Salmonella enterica, which depend on oxygen to multiply and cause gut dysbiosis.

“Our research suggests that one of the best approaches to maintaining gut health might be to feed the beneficial microbes in our intestines dietary fibre, their preferred source of sustenance," said Professor Andreas Bäumler, senior author of the study.

"While it is known that the gut is the site of constant turf wars between microbes, our research suggests that signals generated by beneficial microbes drive the intestinal tract to limit resources that could lead to an expansion of potentially harmful microbes.

"When this host signalling pathway malfunctions, it leads to increased oxygen levels in the gut lumen. These higher oxygen levels make us more susceptible to aerobic enteric pathogens such as Salmonella or Escherichia coli, which use oxygen to edge out competing beneficial microbes," Bäumler added.

The use of dietary fibre to target this signalling mechanism may have potential as an intervention strategy against E. coli or Salmonella infections, suggest the researchers.

Signalling mechanism

The signalling mechanism responsible for maintaining an anaerobic gut environment is a regulatory host receptor known as the peroxisome proliferator–activated receptor-ƴ (PPAR-ƴ). The receptor is able to sense the presence of intracellular butyrate, the SCFA produced by microbial metabolism of dietary fibre.

Butyrate also helps colonic regulatory T-cells (T-regs) to mature and multiply. These cells are also involved with limiting gut inflammation.

Increased PPAR-ƴ signalling drives cells lining the gut to metabolise butyrate by a process known as ß-oxidation. This consumes a considerable amount of oxygen and depletes the amount available to harmful bacteria, explained the researchers.

When PPAR-ƴ signalling is disrupted due to inadequate butyrate, nitrate is generated which disables ß-oxidation, so that free oxygen is no longer consumed.

The researchers found that T-regs cooperated with the PPAR-ƴ to maintain the anaerobic environment in the gut, which in turn enabled beneficial bacteria numbers to multiply.

“Interestingly, the beneficial gut bacteria that are able to breakdown fibre don't survive in an environment rich in oxygen, which means that our microbiota and intestinal cells work together to promote a virtuous cycle that maintains gut health," concluded  first author Mariana Byndloss.

Source: Science
Volume 357, Issue 6351. Published online, doi: 10.1126/science.aam9949
“Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion”
Authors:  Mariana X. Byndloss, Andreas J. Bäumler et al.

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