Abstract
BackgroundThe 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.ResultsThe 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 Ly6Cint monocyte frequencies in spleen and mesenteric lymph nodes add evidence for the potentially anti-inflammatory properties of A. muciniphila.ConclusionsAltogether, 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.
Highlights
The use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention
A. muciniphila supplementation increased mucus thickness in the colon of Ercc1−/Δ7 mice Since A. muciniphila is a mucus-colonizing bacterium and utilizes mucus as energy source, we investigated whether supplementation with A. muciniphila had an effect on the mucus layer in the colon of Ercc1−/Δ7 mice
The results were compared with the mucus thickness of mice supplemented with L. plantarum (WCFS1), since we showed previously that supplementation with this bacterium prevented an age-related decline in mucus thickness [29]
Summary
The use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention. The effects of A. muciniphila on a decline in intestinal health during the aging process are not investigated yet. Coincident with the increase in the aged population that is observed nowadays, the often inevitable decline in overall health in the elderly is becoming an alarming problem. Changes in gut microbiota composition occur, such as a decreased diversity, a decrease in health-promoting bacteria and an increase in potential pathobionts. This disturbed balance in microbiota composition is thought to increase the risk of impaired intestinal barrier function and intestinal inflammation [9]. Transfer of microbiota from aged mice to young germfree recipient mice promoted intestinal inflammation, increased leakage of bacterial components into blood and stimulated systemic immune activation [10]
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