The probiotic L. rhamnosus CNCM I-3690 counteracts pathobiont-driven metabolic effects and gut barrier dysfunction in mice

The prevalence of obesity and related metabolic conditions is increasing worldwide and has become a major public health issue. Recent research has highlighted the gut microbiome’s contribution to the development of non-communicable diseases, although little is known about underlying mechanisms and causal relationships.

A new study led by Prof. Harry Sokol, a gastroenterologist and researcher from the French National Institute for Agricultural Research (INRA) and the French Medical Research Institute (INSERM), has found that the pathobiont Bilophila wadsworthia aggravates high fat diet-induced deleterious metabolic effects in mice, which were partly reversed by a probiotic strain Lactobacillus rhamnosus CNCM I-3690.

Prof. Harry Sokol corresponded with GMFH editors to clarify the study’s results and their clinical relevance for metabolic syndrome pathogenesis.

According to Prof. Sokol: “Over-representation of B. wadsworthia has been associated with animal protein-based diets and diets rich in fats. The negative effect of the increased abundance of this pathobiont on intestinal inflammation had been demonstrated, but despite its documented association with dietary fats, it remained unknown whether B. wadsworthia imposed negative consequences on metabolic host function.”

As expected, a high fat diet (HFD) led to increased fecal B. wadsworthia expansion together with dysregulated glucose-related metabolic parameters compared with mice maintained on the control diet. HFD also modulated gut microbiota composition.

  1. wadsworthia aggravated HFD-induced metabolic impairments, which depended to a certain extent on the levels of B. wadsworthia harbored in the intestine. The altered metabolic parameters included fasting glucose, serum liver enzymes (aspartate transaminase and alanine transaminase), hepatic steatosis and total cholesterol and high-density lipoprotein plasmatic levels. The hepatic lipid content was significantly higher in mice harboring high-density levels of B. wadsworthia compared with those harboring low levels of B. wadsworthia, which shows the synergistic effects of B. wadsworthia and HFD in inducing host metabolic syndrome.

Besides this, B. wadsworthia further potentiated HFD-induced intestinal barrier dysfunction and inflammation and dysregulated bile acid composition in the cecum by increasing levels of conjugated bile acids.

To counteract the negative effects of B. wadsworthia on glucose homeostasis and liver function, the researchers looked at targeting the microbiota through a probiotic. Prof. Sokol explained that the probiotic Lactobacillus rhamnosus strain CNCM I-3690 was selected based on its previously demonstrated anti-inflammatory properties, protective effects against intestinal barrier dysfunction and HFD-induced metabolic alterations in mice, as well as for its ability to induce a reduction in the Desulfobrionaceae family, to which B. wadsworthia belongs. Specifically, L. rhamnosus CNCM I-3690 prevented B. wadsworthia expansion in the cecum and small intestine, suppressed B. wadsworthia-related dysregulation of glucose homeostasis in HFD mice with a higher B. wadsworthia level and corrected the effect of HFD on insulin levels.

Although B. wadsworthia and L. rhamnosus CNCM I-3690 had a slight impact on gut microbiota composition, both affected several pathways involved in inflammation and fat and glucose metabolism. Notably L. rhamnosus CNCM I-3690 corrected the gut microbiota dysfunction induced by B. wadsworthia—such as lower fecal butyrate and propionate concentrations and high taurine conjugated bile acid concentration—as well as intestinal barrier dysfunction.

In conclusion, these findings have shown the contribution of the known pathobiont B. wadsworthia to metabolic pathogenesis. As the administration of L. rhamnosus CNCM I-3690 counteracted some of the deleterious metabolic effect led by B. wadsworthia and dietary lipids, these findings highlight the potential of targeting the gut microbiota and intestinal barrier as a potential therapeutic strategy in managing metabolic diseases.

The fact Bilophila exacerbetes the effect of a high fat diet underscores the need to target the gut microbiome and that probiotics are promising candidates to do so. The fact Bilophila exacerbetes the effect of a high fat diet underscores the need to target the gut microbiome and that probiotics are promising candidates to do so.

According to Prof. Sokol: “A preventive approach using probiotics is particularly relevant in metabolic syndrome. These results open up a new avenue for exploration and they now need to be confirmed in humans. Our next steps are to confirm these results in humans and particularly the effects of L. rhamnosus CNCM I-3690 first on B. wadsworthia levels and secondly on metabolic syndrome markers.”

 

Reference:

Natividad JM, Lamas B, Phuong Pham H, et al. Bilophila wadsworthia aggravates high fat diet induced metabolic dysfunctions in mice. Nat Commun. 2018; 9:2802. doi: 10.1038/s41467-018-05249-7.

Andreu Prados
Andreu Prados
Andreu Prados holds a Bachelor of Science Degree in Pharmacy & Human Nutrition and Dietetics. Science writer specialised in gut microbiota and probiotics, working also as lecturer and consultant in nutrition and healthcare. Follow Andreu on Twitter @andreuprados