Age-Related Colonic Mucosal Microbiome Community Shifts in Monkeys

Abstract

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.

Aging‐related Alzheimer's disease‐like neuropathology and functional decline in captive vervet monkeys (Chlorocebus aethiops sabaeus)

“…Vervets, like humans, exhibit increasing intestinal dysfunction with age (Mitchell et al, 2017). Compared to younger adults, old adults have a lower Firmicutes:Bacteroidetes ratio (Figure 6c), like elder humans, and a lower abundance of butyrate‐producing microbes, consistent with less healthy profiles (Vemuri et al, 2020). Like humans, old vervets have reduced gait speed and sarcopenia.…”

“…Walking speed was calculated as distance/time. (c) Older adult vervets had a lower Firmicutes:Bacteroidetes ratio than did younger adults ( p = .03) (adapted from Vemuri et al, 2020). (d) Two examples from the Wake Forest Maze Task of executive function; examples of an easy (left) maze and difficult (right) maze.…”

Hypertension promotes microbial translocation and dysbiotic shifts in the fecal microbiome of nonhuman primates

“…1,2 A compromised gut barrier makes the gut mucosal lining "leaky", enabling the translocation of microbes or microbial products into the systemic circulation from the gut lumen in a process known as microbial translocation (MT), leading to systemic low-grade endotoxemia and inflammation. [3][4][5] Further, studies have shown that a defective gut barrier alters the composition of the microbes residing in the gut (gut microbiome), resulting in dysbiosis, which worsens overall health. 1,3,[6][7][8][9] Therefore, it is essential to comprehend regulators of the gut barrier and gut microbiome-related changes to help prevent the onset of various chronic diseases.…”

“…Changes in the microbiome result from factors such as aging, environment, diet, activity and other influences, and so looking at the gut microbiome at a number of time points is imperative to capture the true effects. 4,5,9 Due to rapid shifts in the gut microbiome composition and to assess whether the gut barrier and gut microbiota are linked to hypertension, more longitudinal studies are needed.…”

“…14,15 In addition, unlike rodents, NHPs share >93% similarities with the human genome and faithfully recapitulate eating, sleeping and aging patterns. 4,5,15,16 For this purpose, we selected a NHP model, which spontaneously display several key features of human pathophysiology, including hypertension. 14 Therefore, in the present study, we aimed to: (i) crosssectionally investigate the relationship between MT and hypertension (study 1), and (ii) longitudinally examine markers of health, hypertension, gut barrier function, and microbiome in a controlled cohort of NHPs (study 2).…”