Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1−/Δ7 mice

Abstract

Background The use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention. Health benefits attributed to this bacterium include an improvement of metabolic disorders and exerting anti-inflammatory effects. The abundance of A. muciniphila is associated with a healthy gut in early mid- and later life. However, the effects of A. muciniphila on a decline in intestinal health during the aging process are not investigated yet. We supplemented accelerated aging Ercc1 −/Δ7 mice with A. muciniphila for 10 weeks and investigated histological, transcriptional and immunological aspects of intestinal health. Results The thickness of the colonic mucus layer increased about 3-fold after long-term A. muciniphila supplementation and was even significantly thicker compared to mice supplemented with Lactobacillus plantarum WCFS1. Colonic gene expression profiles pointed towards a decreased expression of genes and pathways related to inflammation and immune function, and suggested a decreased presence of B cells in colon. Total B cell frequencies in spleen and mesenteric lymph nodes were not altered after A. muciniphila supplementation. Mature and immature B cell frequencies in bone marrow were increased, whereas B cell precursors were unaffected. These findings implicate that B cell migration rather than production was affected by A. muciniphila supplementation. Gene expression profiles in ileum pointed toward a decrease in metabolic- and immune-related processes and antimicrobial peptide production after A. muciniphila supplementation. Besides, A. muciniphila decreased the frequency of activated CD80 + CD273 − B cells in Peyer’s patches. Additionally, the increased numbers of peritoneal resident macrophages and a decrease in Ly6C int monocyte frequencies in spleen and mesenteric lymph nodes add evidence for the potentially anti-inflammatory properties of A. muciniphila . Conclusions Altogether, we show that supplementation with A. muciniphila prevented the age-related decline in thickness of the colonic mucus layer and attenuated inflammation and immune-related processes at old age. This study implies that A. muciniphila supplementation can contribute to a promotion of healthy aging. Electronic supplementary material The online version of this article (10.1186/s12979-019-0145-z) contains supplementary material, which is available to authorized users.

Akkermansia muciniphila protects intestinal mucosa from damage caused by S. pullorum by initiating proliferation of intestinal epithelium

“…We found that S. pullorum inhibited the production of goblet cells and decreased the expression of Muc2 and Tff2, which caused serious intestinal mucosa damage. It has been previously reported that A. muciniphila can increase mucus thickness and this ability is associated with the secretory function of goblet cells [36]. In our study, treatment with A. muciniphila after damage restored the number of goblet cells, reversing intestinal mucosa damage and increasing the expression of Muc2 and Tff2, which was also confirmed in a previous report [31].…”

Pulse Crop Effects on Gut Microbial Populations, Intestinal Function, and Adiposity in a Mouse Model of Diet-Induced Obesity

“…While lentil and common bean induced, respectively, a 49-fold and 25-fold increase in this bacterium relative to the high-fat control diet, chickpea and dry pea had no effect. The relevance of A. muciniphila is that colonization of the gut with this bacterium has been reported to be inversely associated with obesity, diabetes, and inflammation [74][75][76][77][78][79]. The differential effects of pulse consumption on the content of A. muciniphila is consistent with a selective effect limited to lentil and common bean.…”

Pasteurized Akkermansia muciniphila increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice

“…16 Importantly, the beneficial effects of the bacteria on cardiometabolic features were thereafter supported by others using various pathological murine models. [17][18][19][20][21][22] Recently, we discovered that pasteurization of the bacteria (i.e., treatment for 30 min at 70°C) made it more effective than the live bacteria in preventing DIO in mice. 23 This finding was recently confirmed in a first proof-of-concept pilot human intervention.…”