Aging-related changes in gut microbiome changes impacts host health. The interactive relationship between the microbiome and physiological systems in an aged body system remains to be clearly defined, particularly in the context of inflammation. Therefore, we aimed to evaluate systemic inflammation, microbial translocation (MT) and differences between fecal and mucosal microbiomes. Ascending colon mucosal biopsies, fecal and blood samples from healthy young and old female vervet monkeys were collected for 16S rRNA gene sequencing, MT and cytokine analyses, respectively. To demonstrate microbial co-occurrence patterns, we used Kendall's tau correlation measure of interactions between microbes. We found elevated levels of plasma LBP-1, MCP-1 and CRP in old monkeys, indicative of higher MT and systemic inflammation. Microbiome analysis revealed significant differences specific to age. At the phylum level, abundances of pathobionts such as Proteobacteria were increased in the mucosa of old monkeys. At the family level, Helicobacteriaceae was highly abundant in mucosal samples (old); in contrast, Ruminococcaceae were higher in fecal samples old monkeys. We found significantly lower Firmicutes:Bacteroidetes ratio and lower abundance of butyrate-producing microbes in old monkeys, consistent with less healthy profiles. Microbial community co-occurrence analysis on mucosal samples revealed 13 nodes and 41 associations in the young monkeys, but only 12 nodes and 21 associations in the old monkeys. Our findings provided novel insights into systemic inflammation and gut microbial interactions, highlights the importance of the mucosal niche, and facilitates further understanding of the decline in the stability of the microbial community with aging.
Recent evidence suggests that gut microbiome changes that occur with age impact the health of the host. While it is known that the gut microbiome and physiological systems interact, the relationship between the microbiome in an aged body system remains to be clearly defined, particularly in the context of inflammation. Therefore, we aimed to evaluate systemic inflammation and the mucosal microbiome in young and old female vervet monkeys. Ascending colon mucosal biopsies and blood samples from healthy young and old monkeys were collected for 16S rRNA gene sequencing and cytokine analyses, respectively. To demonstrate microbial cooccurrence patterns, we used Kendall's tau correlation measure of interactions between microbes.We found elevated levels of plasma MCP-1 and CRP in old monkeys, which are indicative of higher systemic inflammation. Microbiome analysis revealed increases in abundance of opportunistic pathobionts such as members of the Proteobacteria phylum in old monkeys. At the family level, abundances of Prevotellaceae and Helicobacteraceae were higher in old monkeys than in young. We also found significantly lower Firmicutes to Bacteroidetes ratio (P= 0.03) and lower abundance of butyrate-producing microbes in old monkeys, consistent with a less healthy profile. Microbial community co-occurrence analysis revealed 13 nodes and 41 associations in the young monkeys, but only 12 nodes and 21 associations in the old monkeys. Our findings provided novel insights into systemic inflammation and gut microbial interactions, highlights the importance of the mucosal niche changes with age, and may facilitate further understanding of the decline in the stability of the microbial community with aging.
Type 2 diabetes (T2D) development may be mediated by skeletal muscle (SkM) function, which is responsible for >80% of circulating glucose uptake. The goals of this study were to assess changes in global and location-level gene expression, remodeling proteins, fibrosis and vascularity of SkM with worsening glycemic control, through RNA sequencing, immunoblotting and immunostaining. We evaluated SkM samples from health-diverse African green monkeys (Cholorcebus aethiops sabaeus) to investigate these relationships. We assessed SkM remodeling at the molecular level by evaluating unbiased transcriptomics in age, sex, and weight and waist circumference-matched metabolically healthy, pre-diabetic (Pre-T2D) and T2D monkeys (n=13). Our analysis applied novel location-specific gene differences and shows that extracellular facing and cell membrane-associated genes and proteins are highly upregulated in metabolic disease. We verified transcript patterns using immunohistochemical staining and protein analyses of MMP16, TIMP2 and VEGF. Extracellular matrix (ECM) functions to support intercellular communications, including the coupling of capillaries to muscle cells, which was worsened with increasing blood glucose. Multiple regression modeling from age- and health-diverse monkeys (n=33) revealed that capillary density was negatively predicted only by fasting blood glucose. The loss of vascularity in SkM co-occurred with reduced expression of hypoxia-sensing genes, which is indicative of a disconnect between altered ECM and reduced endothelial cells, and known perfusion deficiencies present in IR and T2D. This report supports that rising blood glucose values incite ECM remodeling and reduce SkM capillarization, and that targeting ECM would be a rational approach to improve health with metabolic disease.
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