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A new model demonstrates how the gut environment can help neutral mutations become common.

A new model demonstrates how the gut environment can help neutral mutations become common.

Many bacteria species are found in the human body, with most of them located in the stomach. These bacteria are constantly evolving.

Public health issues can arise from the mutation and evolution in gut bacteria. Most studies have focused only on the factors that can influence the evolution and survival of gut bacteria. However, some studies have shown the actual structure of the gut and its hydrodynamic flow.

EPFL and Sorbonne scientists have proposed a new model of diversity and evolution of gut bacteria. This model provides some insight into how the internal guts flow impacts the distribution of gene pool. It shows that neutral mutations are more likely to be prevalent in the gut environment.

The model shows a specific spatial structure of the gut. Hydrodynamics and concentrations gradients can increase the chance that neutral mutants reach high numbers and eventually take over the population.

Professor Anne-Florence Bitbol at EPFL’s School of Life Sciences said, “These neutral mutants refer to bacteria that undergo mutations that have no effect on the growth rate, or at least their impact is negligible in the context of an entire bacterial population.”

The gut’s environment strongly increases the average proportion of neutral mutants. This increases their ability to overtake the population. The gut environment promotes neutral bacterial diversity.

Bitbol ,“The neutral mutants in the gut means that a larger fraction of mutants that appear randomly can reach important fractions instead of rapidly dying out. This can increase diversity and adaptability to environmental changes. And because the composition of the gut microbiota can impact metabolism, this could have indirect implications on metabolism.”

“A key point is that the increase of diversity and of adaptability that we predict is strongly associated with the existence of strong gradients of food and bacterial concentrations in the colon. Bacterial concentrations are much lower in the small intestine than the colon, so there is a lot of food and fewer bacteria at the entrance of the colon.”

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“But further down the intestine, bacteria have eaten the food and reproduced, so there is less food but more bacteria. The model predicts that if these gradients become weaker, diversity enhancement will also decrease. This can occur if the flow velocity changes in the gut or if the contractions or strength of the gut muscles change. This could indicate that there may be metabolic disorders, such as inflammatory-bowel disease. Understanding these effects could potentially be a first step toward learning to alter them to improve such conditions.”

“So far, we have worked on neutral mutants for simplicity, but investigating the case of beneficial mutants those that increase growth rate and deleterious mutants those that decrease growth rate would be extremely interesting and would give a complete picture of the impact of the spatial structure of the gut on the evolution of gut bacteria. There is also a lot to do to increase the realism of the model gradually.”

Journal Reference:

  1. Darka Labavi, Claude Loverdo et al. Hydrodynamic flow in the gut and concentration gradients in it increase neutral bacterial diversity. PNAS 04 January 2022. DOI: 10.1073/pnas.2108671119
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