Modulation of microbiome diversity and cytokine expression is influenced in a sex-dependent manner during aging

Abstract

The microbiome and immune system have a unique interplay, which influences homeostasis within the organism. Both the microbiome and immune system play important roles in health and diseases of the aged including development of cancer, autoimmune disorders, and susceptibility to infection. Various groups have demonstrated divergent changes in the gut microbiota during aging, yet the compounding factor of biological sex within the context of aging remains incompletely understood, and little is known about the effect of housing location in the composition of gut microbiota in the context of both sex and age. To better understand the roles of sex, aging, and location in influencing the gut microbiome, we obtained normal healthy BALB/cByJ mice from a single source and aged male and female mice in two different geographical locations. The 16S rRNA was analyzed from fecal samples of these mice and cytokine levels were measured from serum. 16S rRNA microbiome analysis indicated that both age and sex play a role in microbiome composition, whereas location plays a lesser role in the diversity present. Interestingly, microbiome changes occurred with alterations in serum expression of several different cytokines including IL-10 and IL-6, which were also both differentially regulated in context to sex and aging. We found both IL-10 and IL-6 play a role in the constitutive expression of pSTAT-3 in CD5+ B-1 cells, which are known to regulate the microbiome. Additionally, significant correlations were found between cytokine expression and significantly abundant microbes. Based on these results, we conclude aging mice undergo sex-associated alterations in the gut microbiome and have a distinct cytokine profile. Further, there is significant interplay between B-1 cells and the microbiome which is influenced by aging in a sex-dependent manner. Together, these results illustrate the complex interrelationship among sex, aging, immunity, housing location, and the gut microbiome.

Slowing Alzheimer’s disease progression through probiotic supplementation

“…Evidence suggests that microbiota composition shows sex-related differences ( Elderman et al, 2018 ) that can also affect immunoresponses ( Markle et al, 2013 ; Fischinger et al, 2019 ), and gut microbiota alterations are prominent during the aging process ( Falony et al, 2016 ; DeJong et al, 2020 ). In fact, a recent study demonstrated that microbiome and cytokines profiles were influenced by aging in a sex-dependent manner ( Webster et al, 2022 ). Given the interrelation of sex, age, immunity, and gut microbial composition, it is conceivable that the aging female mice in our study exhibited an exacerbated glia response (ADC group) that could be more responsive to probiotic-induced changes in gut composition (ADP group).…”

β-mannanase-supplemented diets reduced by 85 kcal of metabolizable energy/kg containing xylanase promotes benefits in fecal alpha diversity in lactating sows

“…In the context of the connection between the immune system and the fecal microbiota, multiple investigations have substantiated the impact of cytokines, for example, previous studies 19,20 suggest that the immune system actively controls and regulates the fecal microbiota. This regulation is in uenced by factors such as gender and speci c cytokines, with the strongest interactions observed in the intestine 21 . Therefore, in the present study, our hypothesis that β-mannanase supplementation could modify the abundance, diversity and composition of the fecal microbiome in lactating sows was con rmed, although this did not re ect changes in serum cytokine concentrations.…”

Gut microbiota in regulation of childhood bone growth

“…The gut microbiota has been shown to influence circulating levels of pro-inflammatory cytokines (Mizutani et al, 2022). A recent study by Webster et al (2022) showed that serum IL-1β and IL-6 levels were correlated with the presence of certain bacterial strains in the gut microbiome. Mechanistically, butyrate, one of the SCFAs produced by the gut microbiota, has been shown to inhibit the inflammatory response elicit by lipopolysaccharides, TNFα and interleukins via GRP41 and GRP43, both in endothelial cells (Li et al, 2018) and in chondrocytes (Pirozzi et al, 2018), suggesting that the gut microbiota could stimulate bone growth by reducing inflammation.…”