Brain Gut Microbiome Research Articles

The Gut Microbiome in Health and Disease

The Gut Microbiome in Health and Disease

Brain–Gut Microbiome Interactions and Functional Bowel Disorders

Alterations in the bidirectional interactions between the intestine and the nervous system have important roles in the pathogenesis of irritable bowel syndrome (IBS). A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. A small and poorly defined role for dysbiosis in the development of IBS symptoms has been established through characterization of altered intestinal microbiota in IBS patients and reported improvement of subjective symptoms after its manipulation with prebiotics, probiotics, or antibiotics. It remains to be determined whether IBS symptoms are caused by alterations in brain signaling from the intestine to the microbiota or primary disruption of the microbiota, and whether they are involved in altered interactions between the brain and intestine during development. We review the potential mechanisms involved in the pathogenesis of IBS in different groups of patients. Studies are needed to better characterize alterations to the intestinal microbiome in large cohorts of well-phenotyped patients, and to correlate intestinal metabolites with specific abnormalities in gut-brain interactions.

Reply to McLean et al. and Burnet: The microbiome–gut–brain axis as a pathway toward next generation psychotropics

We thank McLean and colleagues (1) for their comments on our recent study (2). They make two major points. First, they point out that there are differences between the functional effects obtained by them with their Bifidobacteria and those obtained by us with our Lactobacillus strain. To us, this is hardly surprising, and we categorically stated in the Discussion of our paper “Moreover, probiotic effects are strain dependent” (ref. 2, p. 16054). Indeed, it is perfectly conceivable and even likely in our opinion that the effects of probiotics on brain function can occur through different mechanisms, both humoral and neural. Many potential probiotics have been shown to have immune-modulating activity (3) and it is long established that dysregulation in the immune system can bidirectionally affect the brain in a manner relevant to mood and anxiety disorders (4). Second, they argue that models based on infection or colitis may be superior for assessing anxiety-like behavior. We agree that there may be some justification in this position if we were primarily focused on anxiety-like behavior associated with or after infection and inflammation, but the scope of our study was broader and encompassed all aspects of anxiety- and stress-related disorders outside of that aspect comorbid with gastrointestinal disorders. This is the reason we feel our study was an advance on previous exciting research from McLean et al. and others using infection-based models. Heuristically, the fact that modulation of the gut microbiota reverses behavioral effects in an animal model of gastrointestinal dysfunction is perhaps not as surprising as our data (2) that acted as a proof of principle that a potential probiotic bacterium affects a multitude of functional readouts across the brain–gut–microbiome axis under normal physiological conditions or exposure to an acute stressor.