Abstract
BackgroundA dysbiosis in the intestinal microbiome plays a role in the pathogenesis of several immunological diseases. These diseases often show a sex bias, suggesting sex differences in immune responses and in the intestinal microbiome. We hypothesized that sex differences in immune responses are associated with sex differences in microbiota composition.MethodsFecal microbiota composition (MITchip), mRNA expression in intestinal tissue (microarray), and immune cell populations in mesenteric lymph nodes (MLNs) were studied in male and female mice of two mouse strains (C57B1/6OlaHsd and Balb/cOlaHsd). Transcriptomics and microbiota data were combined to identify bacterial species which may potentially be related to sex-specific differences in intestinal immune related genes.ResultsWe found clear sex differences in intestinal microbiota species, diversity, and richness in healthy mice. However, the nature of the sex effects appeared to be determined by the mouse strain as different bacterial species were enriched in males and females of the two strains. For example, Lactobacillus plantarum and Bacteroides distasonis were enriched in B6 females as compared to B6 males, while Bifidobacterium was enriched BALB/c females as compared to BALB/c males. The strain-dependent sex effects were also observed in the expression of immunological genes in the colon. We found that the abundance of various bacteria (e.g., Clostridium leptum et rel.) which were enriched in B6 females positively correlated with the expression of several genes (e.g., Il-2rb, Ccr3, and Cd80) which could be related to immunological functions, such as inflammatory responses and migration of leukocytes. The abundance of several bacteria (e.g., Faecalibacterium prausnitzii et rel. and Coprobacillus et rel.- Clostridium ramosum et rel.) which were enriched in BALB/c males positively correlated to the expression of several genes (e.g., Apoe, Il-1b, and Stat4) related to several immunological functions, such as proliferation and quantity of lymphocytes. The net result was the same, since both mouse strains showed similar sex induced differences in immune cell populations in the MLNs.ConclusionsOur data suggests a correlation between microbiota and intestinal immune populations in a sex and strain-specific way. These findings may contribute to the development of more sex and genetic specific treatments for intestinal-related disorders.
Highlights
A dysbiosis in the intestinal microbiome plays a role in the pathogenesis of several immunological diseases
A higher ratio of Firmicutes/Bacteroidetes was found in Balb/cOlaHsd mice (BALB/c) mice; this ratio was not influenced by sex (Fig. 1c)
We found that C57B1/6OlaHsd mice (B6) females had a relative higher abundance of, among others, Lactobacillus plantarum and Bacteroides distasonis et rel. as compared to B6 males
Summary
A dysbiosis in the intestinal microbiome plays a role in the pathogenesis of several immunological diseases. A disbalance in intestinal microbiota communities (intestinal dysbiosis) has been found to play a significant role in the pathogenesis of a large number of immunological Western diseases, such as inflammatory bowel disease (IBD), other autoimmune diseases, and metabolic syndrome [7, 8]. This growing list of Western-world diseases correlates with changes in microbiota composition [9,10,11]. Some microbiota are involved in the generation of specific regulatory responses in T-cells [12, 15], while others stimulate specific T helper 17 (Th17) cell responses [16]
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