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Background: Males and females have a different predisposition for the development of intestinal disorders, like inflammatory bowel disease (IBD). We hypothesized that sex specific differences in intestinal immune responses may underlie this bias. To test this hypothesis, we studied sex differences in immune cell populations in the Peyer's patches (PP). For comparison with systemic immunity, we studied spleen cells. Methods: Two mouse strains with different susceptibility for developing colitis (BALB/c and C57Bl/6) were used. Using flow cytometry, we measured the percentage of T cells, Th1, Th17, and Treg cells in the PP and spleen. In addition, we measured the percentages of NK cells, macrophages, myeloid, and lymphoid dendritic cells (DCs) and their expression of CD80 and CD103. Moreover, we measured percentages of monocyte subsets in the peripheral circulation. Results were tested using two-way ANOVA, p < 0.05. Results: Males had a lower percentage of T cells in both PP and spleen (PP BALB/c 22.1%, B6 13.6%; spleen BALB/c 4.7%, B6 19.9%) but a higher percentage of Th1 cell in both tissues (PP BALB/c 350%, B6 109.5%; spleen BALB/c 48.7%, B6 41.9%) than females. They also had a higher percentage of Tregs in the spleen than females (BALB/c 20.5%, B6 4.5%). Furthermore, males had a higher percentage of CD80+ DCs in both the PP and spleen (lymphoid DCs in PP BALB/c 104.7%, B6 29.6%; spleen BALB/c 72.2%, B6 44.2%; myeloid DCs in PP BALB/c 80.5%, B6 93.3%; spleen BALB/c 88.5%, B6 50.8%) and a higher percentage of lymphoid CD103+ DCs in the spleen than females (BALB/c 41.5%, B6 28.3%). The percentage of NK cells was decreased in the spleen (BALB/c 12.5%, B6 25.1%) but increased in the PP (BALB/c 75.7%, B6 78.6%) of males as compared with females. Strain differences were also found in the PP; BALB/c mice had a higher percentage of T cells (males 58.1%, females 75.5%), a higher Th/Tc ratio (males 81.0%, females 134.2%), less FoxP3+CD25- T cells (males 14.6%, females 30.0%), more DCs (males 14.8%, females 15.7%) and macrophages (males 67.9%, females 141.2%), and more NK cells (males 160%, females164.3%) than BALB/c mice. Conclusions: In this study, we show sex differences in intestinal and peripheral immune populations. These differences may underlie sex differences in intestinal disorders like IBD, and this information may be an important knowledge for the treatment of intestinal-related diseases. [ABSTRACT FROM AUTHOR]

Background: The use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention. Health benefits attributed to this bacterium include an improvement of metabolic disorders and exerting anti-inflammatory effects. The abundance of A. muciniphila is associated with a healthy gut in early mid- and later life. However, the effects of A. muciniphila on a decline in intestinal health during the aging process are not investigated yet. We supplemented accelerated aging Ercc1−/Δ7 mice with A. muciniphila for 10 weeks and investigated histological, transcriptional and immunological aspects of intestinal health. Results: The thickness of the colonic mucus layer increased about 3-fold after long-term A. muciniphila supplementation and was even significantly thicker compared to mice supplemented with Lactobacillus plantarum WCFS1. Colonic gene expression profiles pointed towards a decreased expression of genes and pathways related to inflammation and immune function, and suggested a decreased presence of B cells in colon. Total B cell frequencies in spleen and mesenteric lymph nodes were not altered after A. muciniphila supplementation. Mature and immature B cell frequencies in bone marrow were increased, whereas B cell precursors were unaffected. These findings implicate that B cell migration rather than production was affected by A. muciniphila supplementation. Gene expression profiles in ileum pointed toward a decrease in metabolic- and immune-related processes and antimicrobial peptide production after A. muciniphila supplementation. Besides, A. muciniphila decreased the frequency of activated CD80+CD273− B cells in Peyer's patches. Additionally, the increased numbers of peritoneal resident macrophages and a decrease in Ly6Cint monocyte frequencies in spleen and mesenteric lymph nodes add evidence for the potentially anti-inflammatory properties of A. muciniphila. Conclusions: Altogether, we show that supplementation with A. muciniphila prevented the age-related decline in thickness of the colonic mucus layer and attenuated inflammation and immune-related processes at old age. This study implies that A. muciniphila supplementation can contribute to a promotion of healthy aging. [ABSTRACT FROM AUTHOR]

Background: The influence of age on basophils is poorly understood, as well as the effect of aging-associated microbiota on basophils. Therefore, we studied the influence of aging and aging-associated microbiota on basophil frequency and phenotype, and differentiation from basophil precursors., Results: Basophils became more abundant in bone marrow (BM) and spleens of 19-month-old mice compared with 4-month-old mice. Aged basophils tended to express less CD200R3 and more CD123, both in BM and spleen. Differences in microbiota composition with aging were confirmed by 16S sequencing. Microbiota transfers from young and old mice to germ-free recipients revealed that CD11b tended to be lowered on splenic basophils by aging-associated microbiota. Furthermore, abundance of Alistipes , Oscillibacter , Bacteroidetes RC9 gut group , and S24-7 family positively correlated and CD123 expression, whereas Akkermansia abundance negatively correlated with basophils numbers.Subsequently, we purified FcεRIα + CD11c - CD117 - BM-derived basophils and found that those from aged mice expressed lower levels of CD11b upon stimulation. Higher frequencies of IL-4 + basophils were generated from basophil precursors of aged mice, which could be reproduced in basophils derived from germ-free recipients of aging-associated microbiota., Conclusions: Collectively, these results show the influence of aging on basophils. Furthermore, this study shows that aging-associated microbiota altered activation of BM-derived basophils in a similar fashion as observed in BM-derived basophils from aged mice., Competing Interests: The experiments were approved by the Animal Ethical Committee of University Medical Center of Groningen.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.