Brain Structure and Response to Emotional Stimuli as Related to Gut Microbial Profiles in Healthy Women

Abstract

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.

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

“…[90] In addition, the composition of the microbiota is associated with differences in affective responses to unpleasant emotional images in healthy females. [95] Supporting these correlational studies, fecal microbiota transfer of samples from depressed individuals has been shown to alter the behavioral profile of recipient microbiota-deficient mice and rats, increasing anxiety-and depression-like behaviors. [90,96] Finally, different probiotic strains have been shown to reduce symptoms of anxiety and depression across several studies in clinical and healthy populations.…”

“…Although two studies failed to find a relationship between overall microbiota composition and amygdala volume in IBS patients and healthy women, [95,123] another identified a particular bacterial phylum that was associated with microstructure of this region. [128] That is, abundance of Actinobacteria correlated with increased fractional anisotropy in the amygdala.…”

“…[129] In healthy women, it has been shown that different microbiota profiles are associated with differences in the patterns of structural white-matter connectivity. [95] The main distinguishing feature was an alteration in the connectivity between an emotion regulation network (including the amygdala) and other brain regions involved in attention and sensory perception. In a separate study by the same group, [35] 4 weeks of a probiotic treatment was sufficient to alter functional network responses to emotional faces in healthy females.…”

“…Morphology Enlarged volume, increases in dendritic length, branch points and spine density in mice [16] No correlation between microbiota composition and amygdala volume in healthy women or IBS patients [95,123] Actinobacteria correlated with enhanced microstructure (increased fractional anisotropy) [128] Activity and connectivity Dampened activity during emotional faces task, altered resting state connectivity with distributed network including hippocampus and thalamus [35] Microbiota profile associated with structural white-matter connectivity in healthy women and with functional connectivity in young children [95,129] Gene expression Specific mRNA expression: NGFI-A, BDNF decreased, NR2B decreased in CeA of mice [5,9] Whole genome sequencing: broad alterations suggestive of upregulation of neuronal activity, differential gene regulation in response to fear and social stimuli [36,101] (Stilling et al, unpublished observations) mRNA expression: Nr3c1, CRH-R1 decreased, BDNF increased in rats [94] Protein expression: BDNF decreased in mice [4] Lactobacillus rhamnosus (JB-1) decreased GABA B1b mRNA in BLA and CeA of mice [62] Broad dysregulation of miRNA in mice [37] www.advancedsciencenews.com www.bioessays-journal.com amygdala was altered for the probiotic-treated participants. Essentially, these data provide the first evidence of a clinical link between the microbiota and functional connectivity of the amygdala.…”

Egyptian Canopic Jars at the Crossroad of Medicine and Archaeology: Overview of 100 Years of Research and Future Scientific Expectations

“…Metagenomics techniques can, in a single run, characterize the genetic material of the host and also of every pathogen present in the sample at the moment of death. Both advantages would be useful for canopic jar analysis, potentially relating organs from the same individual, thanks to genetic profiling, but also in order to screen genetic disorders and pathogens, and even more ambitiously, reconstruct whole microbial communities that live in our body, or microbiome, known to be intimately related with abdomen, neural, inflammatory and immune conditions [66][67][68][69]. Some applied examples: in a confirmation study performed by Shin et al [70] on a 17th century AD Korean Mummy diagnosed with atherosclerotic cardiovascular disease, several risk alleles related with the condition were found, indicating genetic predisposition of the disease.…”