The sex related differences in health and Disease: A systematic review of sex-specific gut microbiota and Possible implications for microbial pathogenesis

Background: The gut microbiota, a complex ecosystem influenced by various physiological and environmental factors, has been increasingly recognized for its role in health and disease. Emerging evidence suggests that sex differences, particularly mediated by sex hormones and physiological variations, significantly influence the composition and diversity of the gut microbiome. This systematic review aimed to evaluate and synthesize the current knowledge on sex-related variations in gut microbiota across human and animal studies. Methods: We conducted a systematic review of 24 eligible studies, selected from an initial 13,205 articles, focusing on healthy populations and next-generation sequencing-based microbiota profiling in both humans and animal models. Results: The results reveal sex-specific differences in microbial diversity and taxa abundance; however, the consistency and significance of these findings vary across studies, with females generally exhibiting higher levels of Akkermansia and Bifidobacterium, while males showed increased levels of Prevotella and Escherichia. These findings suggest that sex may be a contributing, but not necessarily dominant, biological variable shaping microbiome architecture across various species, including mice, pigs, deer, and humans, and highlight the influence of hormonal fluctuations, body composition, and lifestyle factors on gut microbial ecosystems. Conclusion: Our findings underscore the importance of considering sex as a key biological variable in microbiome research and its potential implications for disease susceptibility, therapeutic interventions, and microbiome-targeted strategies in microbial pathogenesis. Moreover, evidence from human studies remains limited, especially those using 16S rRNA gene sequencing, which may lack the resolution to detect strain-level or functional differences. Incorporating multi-omics approaches such as metagenomics, metatranscriptomics, and metabolomics may offer deeper insights into sex-dependent microbial dynamics.However, these implications remain largely associative and require mechanistic validation in future studies.