Obese-type Gut Microbiota Induce Neurobehavioral Changes in the Absence of Obesity - Biological Psychiatry

Background

The prevalence of mental illness, particularly depression and dementia, is increased by obesity.
Here, we test the hypothesis that obesity-associated changes in gut microbiota are intrinsically able to impair neurocognitive behavior in mice.

Methods

Conventionally housed, nonobese, adult male C57BL/6 mice maintained on a normal chow diet were
subjected to a microbiome depletion/transplantation paradigm using microbiota isolated from donors on either a high-fat diet (HFD) or control diet. Following re-colonization, mice were subjected to
comprehensive behavioral and biochemical analyses.

Results

The mice given HFD microbiota had significant and selective disruptions in
exploratory, cognitive, and stereotypical behavior compared with mice
with control diet microbiota in the absence of significant differences
in body weight. Sequencing-based phylogenetic analysis confirmed the
presence of distinct core microbiota between groups, with alterations in
α- and β-diversity, modulation in taxonomic distribution, and
statistically significant alterations to metabolically active taxa. HFD
microbiota also disrupted markers of intestinal barrier function,
increased circulating endotoxin, and increased lymphocyte expression of
ionized calcium-binding adapter molecule 1, toll-like receptor 2, and
toll-like receptor 4. Finally, evaluation of brain homogenates revealed
that HFD-shaped microbiota increased neuroinflammation and disrupted
cerebrovascular homeostasis.

Conclusions

Collectively, these data reinforce the link between gut dysbiosis and neurologic dysfunction and suggest that dietary and/or pharmacologic manipulation of gut microbiota could attenuate the neurologic complications of obesity.