Integrative analysis of gut microbiota composition, host colonic gene expression and intraluminal metabolites in aging C57BL/6J mice

Abstract

The aging process is associated with diminished colonic health. In this study, we applied an integrative approach to reveal potential interactions between determinants of colonic health in aging C57BL/6J mice. Analysis of gut microbiota composition revealed an enrichment of various potential pathobionts, including Desulfovibrio spp., and a decline of the health-promoting Akkermansia spp. and Lactobacillus spp. during aging. Intraluminal concentrations of various metabolites varied between ages and we found evidence for an increased gut permeability at higher age. Colonic gene expression analysis suggested that during the early phase of aging (between 6 and 12 months), expression of genes involved in epithelial-to-mesenchymal transition and (re)organization of the extracellular matrix were increased. Differential expression of these genes was strongly correlated with Bifidobacterium spp. During the later phase of aging (between 12 and 28 months), gene expression profiles pointed towards a diminished antimicrobial defense and were correlated with an uncultured Gastranaerophilales spp. This study demonstrates that aging is associated with pronounced changes in gut microbiota composition and colonic gene expression. Furthermore, the strong correlations between specific bacterial genera and host gene expression may imply that orchestrated interactions take place in the vicinity of the colonic wall and potentially mediate colonic health during aging.

Age-related Changes of Microbiota in Midlife Associated with Reduced Saccharolytic Potential: An In Vitro Study

“…Bi dobacteria dominates in infant gut microbiota and reduces with age. [37] Similar to the observation that Bi dobacterium disappears in middle-aged mice, [12] our data reveal that Bi dobacterium is the genus declined most in human midlife. Furthermore, 8 taxa, including Collinsella and Coriobacteriales (order) and Coriobacteriaceae (family), were observed to decline in midlife.…”

“…decreases strongly and signi cantly in middle-aged mice compared to young subjects. [12] Four genera, including Faecalibacterium, Butyricicoccus, Desulfovibrio and Parasutterella were abundant in young group but absent in midlife group. Faecalibacterium and Butyricicoccus are the main butyrate products found in the intestine.…”

The role of the microbiota in sedentary lifestyle disorders and ageing: lessons from the animal kingdom

“…Older mice also have a different gut microbiome to older mice, and interestingly, co-housing or faecal transfer from adult to aged mice alters microbiome and boosts germinal centre response [80]. The altered gut epithelial gene expression pattern of older mice [81] was correlated with differential abundance of particular species and increased proportional abundance of so-called pathobionts, species such as Escherichia coli and other Proteobacteria that are opportunistic pathogens. Impaired gut barrier function in older mice (evidenced in the previous study by gene expression analysis) was corroborated in another group by leakage of fluorescent markers from the gut lumen into the blood, and this correlated with impaired cognitive function and an altered gut microbiome [82].…”

A human-origin probiotic cocktail ameliorates aging-related leaky gut and inflammation via modulating the microbiota/taurine/tight junction axis

“…Similar to humans, older mice show higher leaky gut, inflammation, microbiome dysbiosis, glucose intolerance, insulin resistance, and physical functions compared with young counterparts (26)(27)(28)(29)(30)(31)(32). By using this model, we studied a multistrain probiotic cocktail isolated from infant gut (33) and defined its functional role in aging-related metabolic dysfunctions, leaky gut, and inflammation in the approximately 80-weekold C57BL/6J mice (equivalent to > 65 years human age).…”