Objective Brain-gut-microbiota interactions may play an important role in human health and behavior. However, while rodent models have demonstrated effects of the gut microbiota on emotional, nociceptive and social behaviors, there is little translational human evidence to date. In this study we identify brain and behavioral characteristics of healthy women clustered by gut microbiota profiles. Methods Forty women supplied fecal samples for 16s rRNA profiling. Microbial clusters were identified using Partitioning Around Medoids. Functional magnetic resonance imaging was acquired. Microbiota-based group differences were analyzed in response to affective images. Structural and diffusion tensor imaging provided gray matter metrics (volume, cortical thickness, mean curvature, surface area) as well as fiber density between regions. A sparse Partial Least Square-Discrimination Analysis was applied to discriminate microbiota-clusters using white and gray matter metrics. Results Two bacterial genus-based clusters were identified, one with greater Bacteroides abundance (n=33), one with greater Prevotella abundance (n=7). The Prevotella group showed less hippocampal activity viewing negative valences images. White and gray matter imaging discriminated the two clusters, with accuracy of 66.7% and 87.2% respectively. The Prevotella cluster was associated with differences in emotional, attentional, and sensory processing regions. For gray matter, the Bacteroides cluster showed greater prominence in the cerebellum, frontal regions, and the hippocampus. Conclusions These results support the concept of brain-gut-microbiota interactions in healthy humans. Further examination of the interaction between gut microbes, brain and affect in humans is needed to inform preclinical reports that microbial modulation may affect mood and behavior.

Localized provoked vulvodynia (LPVD) affects approximately 16% of the female population, but biological mechanisms underlying symptoms remain unknown. Like in other, often comorbid chronic pain disorders, altered sensory processing and modulation of pain, including central sensitization, dysregulation of endogenous pain modulatory systems, and attentional enhancement of pain perception have been implicated. The aim of this study was to test whether regions of interest showing differences in LPVD compared to healthy controls (HCs) in structural and evoked-pain neuroimaging studies, also show alterations in during rest compared to HCs and a chronic pain control group (irritable bowel syndrome, IBS). Functional magnetic resonance imaging was performed during resting state in 87 age-matched premenopausal females (29 LPVD, 29 HCs, 29 IBS). Group independent component analysis and general linear models were applied to investigate group differences in the intrinsic connectivity of regions comprising sensorimotor, salience, and default mode resting state networks. LPVD subjects showed substantial alterations in the intrinsic connectivity of these networks compared to HCs and IBS. The intrinsic connectivity of many of the regions showing group differences during rest were moderately associated with clinical symptom reports in LPVD. Findings were robust to controlling for affect and medication usage. The current findings indicate LPVD subjects have alterations in the intrinsic connectivity of regions comprising the sensorimotor, salience, and default mode networks. Although shared brain mechanisms between different chronic pain disorders have been postulated, the current findings suggest some alterations in functional connectivity may show disease specificity.

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