Sex shapes gut–microbiota–brain communication and disease

Abstract

Research into the microbiota–gut–brain axis (MGBA) has entered a golden age, raising the hope that therapeutics acting on it may offer breakthroughs in the treatment of many illnesses. However, most of this work overlooks a fundamental, yet understudied, biological variable: sex. Sex differences exist at every level of the MGBA. Sex steroids shape the structure of the gut microbiota, and these microbes in turn regulate levels of bioactive sex steroids. These hormones and microbes act on gut sensory enteroendocrine cells, which modulate downstream activity in the enteric nervous system, vagus nerve, and brain. We examine recent advances in this field, and discuss the scientific and moral imperative to include females in biomedical research, using autism spectrum disorder (ASD) as an example.