Gut commensal Bacteroides faecichinchillae, a potential novel candidate of next-generation probiotics targeting type 2 diabetes
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Abstract
The implication of gut microbiota in the pathophysiology of type 2 diabetes, one of the major health concerns worldwide, has demonstrated the benefits of using probiotics to improve dysbiosis. Facing the lack of defined research strategy to found and qualify bacterial with real antidiabetic activity, we have developed a program to identify, select and validate novel strains able to improve metabolic alterations in type 2 diabetes. Among potential candidates, we identified Bacteroides faecichinchillae (named BAfa hereafter), and the present work presents the validation of the antidiabetic potential of the ST37 (DSMZ 26883) BAfa strain in mice fed a high-fat high-sucrose (HFS) diet for 10 weeks followed by 4 weeks of treatment. Daily gavage with live, but not heat inactivated, BAfa improved glucose tolerance, fasting hyperinsulinemia and liver triglyceride content in HFS fed mice. Furthermore, these beneficial effects were retained after lyophilization. Using this preclinical model, we characterised BAfa mechanism of action, showing that four weeks of treatment was associated with reduced hepatic accumulation of ceramides, key actors of insulin resistance. The underlying mechanism could be related to BAfa-induced changes in the intestinal bile acid profile and inhibition of the Fxr-Fgf15 pathway in the ileum. BAfa supplementation during 4 weeks in HFS fed mice was also associated with mild modifications of gut microbiota composition, with the upregulation of several species known for their beneficial metabolic actions (such as Lactobacillus johnsonii, Limosilactobacillus reutei, Roseburia, Turicimonas muris, Phocaeicola dorei or Akkermansia muciniphila) and for being up-regulated during metformin treatment. Altogether, these data indicate that BAfa and related B. faecichinchillae strains could be considered for developing next-generation probiotics to treat type 2 diabetes, potentially in combination with the anti-diabetic drug metformin.
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Gut commensal Bacteroides faecichinchillae, a potential novel candidate of next-generation probiotics targeting type 2 diabetes
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Abstract
The implication of gut microbiota in the pathophysiology of type 2 diabetes, one of the major health concerns worldwide, has demonstrated the benefits of using probiotics to improve dysbiosis. Facing the lack of defined research strategy to found and qualify bacterial with real antidiabetic activity, we have developed a program to identify, select and validate novel strains able to improve metabolic alterations in type 2 diabetes. Among potential candidates, we identified Bacteroides faecichinchillae (named BAfa hereafter), and the present work presents the validation of the antidiabetic potential of the ST37 (DSMZ 26883) BAfa strain in mice fed a high-fat high-sucrose (HFS) diet for 10 weeks followed by 4 weeks of treatment. Daily gavage with live, but not heat inactivated, BAfa improved glucose tolerance, fasting hyperinsulinemia and liver triglyceride content in HFS fed mice. Furthermore, these beneficial effects were retained after lyophilization. Using this preclinical model, we characterised BAfa mechanism of action, showing that four weeks of treatment was associated with reduced hepatic accumulation of ceramides, key actors of insulin resistance. The underlying mechanism could be related to BAfa-induced changes in the intestinal bile acid profile and inhibition of the Fxr-Fgf15 pathway in the ileum. BAfa supplementation during 4 weeks in HFS fed mice was also associated with mild modifications of gut microbiota composition, with the upregulation of several species known for their beneficial metabolic actions (such as Lactobacillus johnsonii, Limosilactobacillus reutei, Roseburia, Turicimonas muris, Phocaeicola dorei or Akkermansia muciniphila) and for being up-regulated during metformin treatment. Altogether, these data indicate that BAfa and related B. faecichinchillae strains could be considered for developing next-generation probiotics to treat type 2 diabetes, potentially in combination with the anti-diabetic drug metformin.
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