MyNewGut researchers found that slight differences in the structure of bacterial metabolites may result in markedly different effects on the gut cells. Gut bacteria help to break down parts of the food we have eaten, causing them to produce metabolites. These bacterial metabolites can have both negative and positive effects on the gut, notably depending on their concentrations in the intestinal contents.
A new intervention study using human volunteers was performed by MyNewGut researchers. They found in human volunteers, that some bacterial metabolites produced by the gut microbiota present at high concentrations in fecal water were associated with high cytotoxic potential towards colonic epithelial cells; meaning that these metabolites can decrease cell viability. This was the case notably for hydroxphenylacetic acid (HO-PAA) which was associated with high cytotoxic potential.
They then tested the effects of HO-PAA at concentrations close to the one’s found in the feces on colonic cells and compared the effects obtained with another metabolite with similar chemical structure, namely phenylacetic acid (PAA). High concentrations of HO-PAA showed an increase in the potential for it to cause harm to the gut cells. Indeed, HO-PAA reduced the cell energy metabolism, increased the production of oxygen reactive species and affected the DNA integrity, whereas PAA had no effect on these parameters. However, PAA displayed a slight cytotoxic effect on intestinal cells; an effect that was not observed for HO-PAA.
The results showed that HO-PAA at high concentrations is genotoxic for colonic intestinal cells while PAA, although not genotoxic for intestinal cells, did display potential for cell toxicity.
From these results,we conclude that slight differences in the structure of bacterial metabolites can be associated with significantly different effects on colonocytes in terms of cytotoxic and genotoxic effects. In addition, our results suggest that HO-PAA present in the fecal water extract does not have a great influence on the cytotoxic effect of the mixture.
Nutritional strategies can be considered which would allow concentrations of harmful bacterial metabolites to be maintained (either cytotoxic or genotoxic) in the intestinal content below the harmful threshold. Undigested alimentary compounds are able to bind to these bacterial metabolites, thus preventing their harmful effect on the intestinal cells.