Vasopressin deletion is associated with sex-specific shifts in the gut microbiome

Abstract

Brattleboro rats harbor a spontaneous deletion of the arginine-vasopressin (Avp) gene. In addition to diabetes insipidus, these rats exhibit low levels of anxiety and depressive behaviors. Recent work on the gut-brain axis has revealed that gut microbiota can influence anxiety behaviors. Therefore, we studied the effects of Avp gene deletion on gut microbiota. Since Avp gene expression is sexually different, we also examined how Avp deletion affects sex differences in gut microbiota. Males and females show modest but differentiated shifts in taxa abundance across 3 separate Avp deletion genotypes: wildtype (WT), heterozygous (Het) and AVP-deficient Brattleboro (KO) rats. For each sex, we found examples of taxa that have been shown to modulate anxiety behavior, in a manner that correlates with anxiety behavior observed in homozygous knockout Brattleboro rats. One prominent example is Lactobacillus, which has been reported to be anxiolytic: Lactobacillus was found to increase in abundance in inverse proportion to increasing gene dosage (most abundant in KO rats). This genotype effect of Lactobacillus abundance was not found when females were analyzed independently. Therefore, Avp deletion appears to affect microbiota composition in a sexually differentiated manner.

The role of the microbiome in the neurobiology of social behaviour

“…There is also recent, intriguing evidence from rats that deletion of the Avp gene (which controls vasopressin expression in the brain) leads to sex-specific changes in the composition of the microbiome, including an increase in Lactobacillus spp. in males (Fields et al, 2018). The indolamine serotonin (5-hydroxytryptamine) is a metabolite of the essential amino acid tryptophan.…”

Gene-by-Sex Interactions in Mitochondrial Functions and Cardio-Metabolic Traits

“…Sex differences in susceptibility to obesity, insulin resistance, and other cardio-metabolic traits have been amply described in mice, humans, and other species, with females generally ex-hibiting beneficial metabolic profiles (Karp et al, 2017;Kenney-Hunt et al, 2008;Mittelstrass et al, 2011;Ober et al, 2008;Parks et al, 2015;Varlamov et al, 2014;White and Tchoukalova, 2014;Yang et al, 2006). Sex differences have also recently been identified for the gut microbiome (Fields et al, 2017;Org et al, 2016). Gene expression studies show that a large proportion of genes are differentially expressed in adipose, liver, brain, and other tissues (Della Torre et al, 2018;Kwekel et al, 2017;Yang et al, 2006) and that sex hormones as well as chromosome complement play a major role in modulation of gene expression (Kukurba et al, 2016;Mozhui et al, 2012;Rinn and Snyder, 2005;Vieira Potter et al, 2012;Yang et al, 2006).…”

Alterations of gut microbiota composition in post-finasteride patients: a pilot study

“…A relationship between gut microbiota population and steroid environment has been also proposed [45,56,57]. Indeed, gonadectomy and hormone replacement have a clear effect on gut bacteria in rodents [58][59][60][61][62][63], for instance, the changes observed in Ruminococcaceae after orchidectomy in mice [58]. Alteration in Ruminococcaceae also occurred in prostate cancer patients treated with oral androgen receptor axis-targeted therapies [64].…”