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1AbstractA body of pre-clinical evidence shows how the gut microbiota influence brain functioning, including brain connectivity. A growing number of studies have investigated the association between the gut microbiota and brain connectivity in humans. Linking brain connectivity measures 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, includingPrevotella,Bacteroides,RuminococcusandBlautiawere most consistently reported in association with brain connectivity. Additionally, 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. Altogether, based on our synthesis, there is evidence for an association between the gut microbiota and brain connectivity. However, the specificity of the signal is yet unclear as most findings were poorly replicated across studies. 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 employ data-driven multivariate analysis strategy.

Benefits of exploring the effect of the gut microbiota on the brain Danique Mulder, Mirjam Bloemendaal & Alejandro Arias Vásquez from the departments of Psychiatry & Human Genetics, Radboud University Medical Center, look at gut microbiota and our understanding of its effects on the human brain. Dr. Christof Koch, Chief Scientist and President of the Allen Institute for Brain Science once said: “We don’t even understand the brain of a worm,” when asked how close we were to understanding how the human brain works (1). One thing we have been able to discover is that our brain does not function fractionated or in isolation. A wealth of brain studies tells us, in fact, that multiple and sometimes large areas of the brain are involved in even the most mundane memory tasks and when strong emotions are involved, millions of neurons can become more active and help us modify behaviors. Moreover, the brain is intrinsically linked with other bodily functions, including those taking place in the gastro-intestinal tract (GIt).