The role of gender-gut microbiota interaction in the development of neuropsychiatric and metabolic disorders

Two review articles, recently published in the scientific journal Biology of Sex Differences, analyzed the role of gender-gut microbiota interaction in the development and onset of particular neuropsychiatric and metabolic disorders.

Human and animal studies have found important gender-specific differences in the composition of the gut microbiota. Human studies have demonstrated that the male and female microbiota differ at the bacterial phyla, genus, and species, with greater diversity in the females. Gender-specific differences in the gut microbiota appear significantly after puberty, indicating an early separation of the developmental trajectories between males and females. By contrast, the microbiota of postmenopausal women becomes more similar to that of men.

The influence of gonadal steroids on the gut microbiota is reflected in both genders. However, this influence is especially important in women due to the hormonal fluctuations in puberty, pregnancy and menopause. It is believed that gut microbiota and estrogen have bi-directional interactions. Several studies have shown that bilateral ovariectomy in mice can lead to microbial dysbiosis and an increase in Clostridium bolteae. The gut microbiota, on the other hand, regulates estrogen levels by mediating the metabolism of estrogens in the enterohepatic circulation. In addition, men or women with an elevated serum level of testosterone or estradiol have a more diverse gut microbiota. It has been found that the number of bacterial genera correlates with levels of gonadal steroids.

About the studies

The first review of Shobeiri P, et al summarizes the current literature on the reciprocal interaction between gender-related cerebral differences and gut microbiota, and its role in the development of particular neuropsychiatric disorders via influencing the gut–brain axis.

Gut microbes communicate with the central nervous system (CNS) through at least three parallel and interactive channels, involving nervous, endocrine, and immune signaling.

Certain types of intestinal microbiota are capable of producing and releasing neurotransmitters such as GABA, serotonin, catecholamine, and histamine at a local level. These bacteria-generated neurotransmitters can communicate with the CNS through enterochromaffin cells and enteric nerve receptors. In addition, the gut microbiota can activate the vagus nerve, and this stimulation has a significant impact on the brain. Tryptophan deficiency has been linked to clinical depression, and tryptophan metabolism appears to be affected by the gut microbiota.

At the same time, the brain affects the structure and function of the gut microbiota through the autonomic nervous system. The autonomic nervous system modulates gut motility and permeability, intestinal transit and secretion, and potentially the secretion of hormones which directly modulate microbial gene expression.

The scientists also discussed the considerable influence of interaction between gender-specific brain differences and gut microbiota over the emergence of particular neuropsychiatric disorders. These disorders include generalized anxiety disorder, major depressive disorder, eating disorders (anorexia nervosa and bulimia nervosa), neurodevelopmental disorders (autism spectrum disorders, attention deficit hyperactivity disorder) and neurodegenerative disorders (Alzheimer’s disease and Parkinson’s disease).

The authors concluded that genetic factors and gonadal steroids are the primary mediators of such differences. The further research is needed to explore the influence of gender-specific gut-brain-axis over a variety of neuropsychiatric disorders.

This review was published in the peer-reviewed journal Biology of Sex Differences. Shobeiri P. et al. Shedding light on biological sex differences and microbiota–gut–brain axis: a comprehensive review of its roles in neuropsychiatric disorders. Biol Sex Differ 13, 12 (2022). (Open-Access).

In the second review, Santos-Marcos JA, et al. discuss gender-related differences in the development and prevalence of metabolic diseases, with particular emphasis on obesity, metabolic syndrome and type 2 diabetes.

Metabolic diseases, like obesity, metabolic syndrome and type 2 diabetes display gender-specific differences in their development and prevalence. The changes in the gut microbiota associated with metabolic diseases are different in men and women.

The scientists analyzed the interplay between gonadal steroids and the gut microbiota in the development of metabolic diseases, and how sex hormones influence the onset and prevalence of metabolic diseases, like obesity, metabolic syndrome and type 2 diabetes.

According to the authors, the main factors involved in these pathologies include lipopolysaccharide (endotoxin of the external membrane of Gram-negative bacteria involved in chronic inflammation), inflammation (gut microbiota has been linked to diseases characterized by chronic inflammation of low-level), the integrity of the gut barrier (the gut microbiota is known to influence the integrity and permeability of the intestinal barrier and therefore the inflammatory state), metabolites derived from the gut microbiota (short-chain fatty acids from bacterial fermentation of dietary fibers have been associated with reduced inflammation), and gut–brain axis.

This article was published in the scientific journal Biology of Sex Differences. Santos-Marcos JA et al. Interaction between gut microbiota and sex hormones and their relation to sexual dimorphism in metabolic diseases. Biology of Sex Differences (2023) 14:4. (Open Access)