Oral Indole-3-acetate Supplementation Increases the Abundance of Bifidobacterium pseudolongum and Akkermansia muciniphila in the Intestine of Mice on a High-Fat Diet

Abstract— Objective: It is known that even a short-term high-fat diet has a negative effect on the metabolic health of the organism. However, under the influence of diet, first of all, the intestinal microbiota undergoes changes. The type of diet, dietary supplements and drugs affect both the taxonomic diversity of the microbiota and its functional state. It is known that with the participation of the intestinal microbiota, tryptophan is converted into indole and its various derivatives. The leading role of indoles in the regulation of the expression of tight junction proteins, and accordingly the regulation of intestinal permeability, has also been established. The aim of our study was to assess the effect of indole-3-acetate on the taxonomic diversity of the microbiota of the small and large intestines, as well as to establish the potential prebiotic value of this indole derivative under conditions of short-term use of a high-fat diet. Methods: C57/black6 SPF mice aged 4–5 weeks (n = 60, females) were randomly divided into six groups. A high-fat diet was achieved by feeding laboratory animals a high-fat diet of animal origin, providing up to 30% of the total calories. Indole-3-acetate was administered together with a standard or high-fat diet via an atraumatic intragastric tube at a single dose of 0.1392 mg per mouse for 28 days. Results and Discussion: In our study, we showed for the first time that in C57/black6 SPF mice on a short-term high-fat diet, indole-3-acetate increases the representation of Bifidobacterium pseudolongum in the microbial community of both the small intestine and the large intestine. Whereas the increase in Akkermansia muciniphila was only in the microbial community of the large intestine. Indole-3-acetate intake provides normoglycemia in animals on a short-term high-fat diet. Conclusions: The use of indole-3-acetate in various metabolic diseases associated with a high-fat diet and dysbacteriosis may be a promising therapeutic approach to correct metabolic disorders through modulation of the microbiotic community.