The Impact of Gut Microbiota on Gender-Specific Differences in Immunity

Abstract

Males and females are known to have gender-specific differences in their immune system and gut microbiota composition. Whether these differences in gut microbiota composition are a cause or consequence of differences in the immune system is not known. To investigate this issue, gut microbiota from conventional males or females was transferred to germ-free (GF) animals of the same or opposing gender. We demonstrate that microbiota-independent gender differences in immunity are already present in GF mice. In particular, type I interferon signaling was enhanced in the intestine of GF females. Presumably, due to these immune differences bacterial groups, such as Alistipes, Rikenella, and Porphyromonadaceae, known to expand in the absence of innate immune defense mechanism were overrepresented in the male microbiota. The presence of these bacterial groups was associated with induction of weight loss, inflammation, and DNA damage upon transfer of the male microbiota to female GF recipients. In summary, our data suggest that microbiota-independent gender differences in the immune system select a gender-specific gut microbiota composition, which in turn further contributes to gender differences in the immune system.

The microgenderome revealed: sex differences in bidirectional interactions between the microbiota, hormones, immunity and disease susceptibility

“…Female mice receiving female transplants maintained their normal body mass, whereas females receiving male microbiota or male recipients of either male or female microbiota lost weight, suggesting the female microbiota may be less pro-inflammatory, further confirmed by the analysis of local genes and pathways affected in these experiments [43]. The microbiota first adapts to the sex of the recipient, but by 4 weeks, some donor-specific sex differences become apparent [43]. Mice receiving female microbiota had higher levels of double-negative T cell precursors compared to mice receiving male microbiota, suggesting a sex-dependent effect of the GIT microbiota on T cell development [43].…”

“…These sex differences in the microbiota have been shown to correlate with sex differences in GIT expression of multiple genes controlling immunological function, including genes affecting inflammation and leukocyte migration [44]. For instance, in a study examining differential gene expression in the GIT mucosa, males had greater transforming growth factor beta (TGF-β), interleukin 1 beta (IL-1β) signalling, and type 1 interferon (IFN) pathway regulation than females [43], further suggesting the important role sex plays in the microbiota-immunity interface.…”

“…A recent study addressed this reciprocal relationship by performing GIT microbiota transfer experiments from conventional [i.e., specific pathogen free (SPF)] to germ-free (GF) mice of the same or opposite sex, and examining effects on weight loss, organ-specific T and B cell immunity and gene expression in the GIT [43]. Female mice receiving female transplants maintained their normal body mass, whereas females receiving male microbiota or male recipients of either male or female microbiota lost weight, suggesting the female microbiota may be less pro-inflammatory, further confirmed by the analysis of local genes and pathways affected in these experiments [43]. The microbiota first adapts to the sex of the recipient, but by 4 weeks, some donor-specific sex differences become apparent [43].…”

“…The microbiota first adapts to the sex of the recipient, but by 4 weeks, some donor-specific sex differences become apparent [43]. Mice receiving female microbiota had higher levels of double-negative T cell precursors compared to mice receiving male microbiota, suggesting a sex-dependent effect of the GIT microbiota on T cell development [43]. However, there were no sex differences in T helper (Th) types Th1, Th2 or Th17 cell subsets in PP, mesenteric lymph nodes (MLNs) or spleens [43].…”

“…Mice receiving female microbiota had higher levels of double-negative T cell precursors compared to mice receiving male microbiota, suggesting a sex-dependent effect of the GIT microbiota on T cell development [43]. However, there were no sex differences in T helper (Th) types Th1, Th2 or Th17 cell subsets in PP, mesenteric lymph nodes (MLNs) or spleens [43]. In another study, transfer ofmale microbiota to GF males led to greater RORγt+ Foxp3+ T cells (i.e.…”