A systematic review exploring the association between the human gut microbiota and brain connectivity in health and disease

Abstract

A body of pre-clinical evidence shows how the gut microbiota influence brain functioning, including brain connectivity. Linking measures of brain connectivity to the gut microbiota can provide important mechanistic insights into the bi-directional gut-brain communication. In this systematic review, we therefore synthesized the available literature assessing this association, evaluating the degree of consistency in microbiota-connectivity associations. Following the PRISMA guidelines, a PubMed search was conducted, including studies published up to September 1, 2022. We identified 16 studies that met the inclusion criteria. Several bacterial genera, including Prevotella, Bacteroides, Ruminococcus, Blautia, and Collinsella were most frequently reported in association with brain connectivity. Additionally, connectivity of the salience (specifically the insula and anterior cingulate cortex), default mode, and frontoparietal networks were most frequently associated with the gut microbiota, both in terms of microbial diversity and composition. There was no discernible pattern in the association between microbiota and brain connectivity. Altogether, based on our synthesis, there is evidence for an association between the gut microbiota and brain connectivity. However, many findings were poorly replicated across studies, and the specificity of the association is yet unclear. The current studies show substantial inter-study heterogeneity in methodology and reporting, limiting the robustness and reproducibility of the findings and emphasizing the need to harmonize methodological approaches. To enhance comparability and replicability, future research should focus on further standardizing processing pipelines and employing data-driven multivariate analysis strategies.

Brain signatures of chronic gut inflammation

“…Aberrant connectivity between nodes of the salience network (SN) (16,19), including the anterior cingulate and insula cortex, further supports the possibility that IBD individuals experience altered interoceptive processing of visceral sensations (e.g., nociceptive, inflammatory, or microbial-related stimuli) (26). In a recent meta-analysis exploring the association between the human gut microbiota and functional connectivity, the highest level of consistency was found for the DMN, frontoparietal (FPN), and SN [particularly the insula and anterior cingulate cortex (27)]. Given the relationship between the DMN and SN in anxiety and depression, the reported alterations in patients with IBD may be of substantial clinical importance.…”

Dietary (Poly)phenols and the Gut–Brain Axis in Ageing

“…However, the different biological activities of various (poly)phenols will depend both on their bioavailability, itself influenced by factors such as age, sex and body composition, and on their secondary metabolites produced by the gut microbes [60,61], potentially explaining inter-individual variability in response to (poly)phenol intake [65]. Evidence that interactions exist between (poly)phenols and brain health, mediated via effects on the gut microbiome and inflammatory pathways, is compelling and widely reported [66], but whether products of polyphenol-mediated gut microbial metabolism are associated with brain activity is far less well-established [67].…”

Sex Differences in Visceral Pain and Comorbidities: Clinical Outcomes, Preclinical Models, and Cellular and Molecular Mechanisms

“…The connectivity between brain areas and other components in the pain pathway are implicated in the regulation of chronic pain. The connectivity includes but is not limited to microbiota-gut-brain connections [158,159], the functional interactions within the brain [160,161], and the connectivity of brain and the descending pain antinociceptive system [162]. Emerging evidence points out the ACC, a key brain area in pain processing, as a therapeutic target for central neuromodulation in clinical pain management [163][164][165].…”