Sex differences in the phylum‐level human gut microbiota composition

Koliada et al. BMC Microbiology (2021) 21:131 https://doi.org/10.1186/s12866-021-02198-y RESEARCH Open Access Sex differences in the phylum‐level human gut microbiota composition Alexander Koliada1, Vladislav Moseiko1, Mariana Romanenko2, Oleh Lushchak3,4, Nadiia Kryzhanovska5, Vitaly Guryanov6 and Alexander Vaiserman2* Abstract Background: Evidence was previously provided for sex-related differences in the human gut microbiota composition, and sex-specific discrepancy in hormonal profiles was proposed as a main determinant of these differences. On the basis of these findings, the assumption was made on the role of microbiota in the sexual dimorphism of human diseases. To date, sex differences in fecal microbiota were demonstrated primarily at lower taxonomic levels, whereas phylum-level differences between sexes were reported in few studies only. In the present population-based cross-sectional research, sex differences in the phylum-level human gut microbiota composition were identified in a large (total n = 2301) sample of relatively healthy individuals from Ukraine. Results: Relative abundances of Firmicutes and Actinobacteria, as determined by qRT-PCR, were found to be significantly increased, while that of Bacteroidetes was significantly decreased in females compared to males. The Firmicutes to Bacteroidetes (F/B) ratio was significantly increased in females compared to males. Females had 31 % higher odds of having F/B ratio more than 1 than males. This trend was evident in all age groups. The difference between sexes was even more pronounced in the elder individuals (50+): in this age group, female participants had 56 % higher odds of having F/B ratio > 1 than the male ones. Conclusions: In conclusion, sex-specific differences in the phylum-level intestinal microbiota composition were observed in the Ukraine population. The F/B ratio was significantly increased in females compared to males. Further investigation is needed to draw strong conclusions regarding the mechanistic basis for sex-specific differences in the gut microbiota composition and regarding the role of these differences in the initiation and progression of human chronic diseases. Keywords: Gut microbiota composition, Firmicutes to Bacteroidetes ratio, Sex-specific differences, Hormonal profile Background A wide range of microorganisms inhabit various sites of the human body, such as the skin, oral cavity and vagina, but most of them reside in the gut. Convincing evidence indicates that composition of the bacterial community inhabiting the gastrointestinal tract (gut microbiota) contributes significantly to host metabolic and immune functions, thereby substantially affecting its health status * Correspondence: 2 Institute of Gerontology, Vyshgorodskaya st. 67, 04114 Kyiv, Ukraine Full list of author information is available at the end of the article [1, 2]. The human intestinal microbiome (the genetic material of all microorganisms, including bacteria and also some viruses and fungi, that colonize the intestine) is known to be established early in life and remains relatively stable during adult life, but differs between individuals depending on genotype, body mass index (BMI), lifestyle, physical activity, and also dietary and cultural habits [3]. Multiple findings from animal and human studies indicate that sex may also be a potentially important factor in determining the microbiome composition (for review, see ref. [4]). However, it is often ignored by researchers even despite its potential importance. In © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Koliada et al. BMC Microbiology (2021) 21:131 several recent studies, evidence for sex-related differences in the composition of intestinal microbiome was shown, and sex-specific discrepancy in hormonal profiles was proposed to be a major determinant of these differences [5]. The host and microbiota communicate in a bidirectional manner, affecting each other’s functions. In particular, gut microbiota plays a key role in maintaining normal testosterone levels, estrous cycle, and reproductive functions [6]. Moreover, intestinal microorganisms have been shown to be involved in enterohepatic recirculation of estrogens and androgens, as well as in affecting local and systemic levels of sex steroid hormones and in generating androgens from glucocorticoids [6]. Furthermore, the potential role of microbiota in shaping sexually dimorphic immunity was suggested [7]. These sex-specific differences in microbiota composition can likely contribute to sexrelated distinction in local gastrointestinal inflammation, systemic immune responses and susceptibility to inflammatory disorders [8]. In addition, the gut microbiota has been repeatedly shown to be an important causal factor in pathogenesis of cardio-metabolic disorders, such as impaired glucose regulation, atherosclerosis, hypertension, dyslipidemia, obesity and type 2 diabetes [9, 10] as well as neurological disorders [11], for which sexual dimorphism in disease onset and progression has been consistently reported. Moreover, changes in the gut microbiome can likely contribute to the higher prevalence of autoimmune diseases in women than in men [12] and to health concerns in menopausal women [13]. The assumption on the potential role of gut microbiota in the sexual dimorphism of human diseases, however, remains mostly hypothetical. To date, the meaningful empirical evidence for sexspecific differences in the intestinal microbiota composition was reported mostly in animal models, while findings Page 2 of 9 from human populations are rather inconsistent and inconclusive perhaps due to the many confounding factors involved [4]. In addition, most of this evidence comes from small sample size studies which does not allow for causal inference. Therefore, further research is needed in order to better understand sex-related differences in the composition of human intestinal microbiome. In (...truncated)