Vasopressin deletion is associated with shifts in the gut microbiota

BACKGROUND: Brattleboro rats harbor a spontaneous deletion of the arginine-vasopressin (Avp) gene. In addition to diabetes insipidus, these rats show low levels of anxiety and depressive behaviors and harbor a hypo-responsive immune system. Recent work on the gut-brain axis has revealed that gut microbiota can also modify anxiety behaviors and immune status. Therefore, we studied the effects of Avp gene deletion on gut microbiota. Since Avp gene expression is sexually different, we also studied how Avp deletion affects sex differences in gut microbiota. RESULTS: Males and females show modest but distinctive shifts in taxa abundance across three 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 and inflammation, in a manner that correlates with anxiety behavior and immunity 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. Furthermore, we found that sex differences in taxa abundance differ between the three separate genotypes.CONCLUSIONS: Brattleboro rats harbor a distinct microbiota, which may independently affect behavioral phenotypes observed in this rodent model. Furthermore, Avp appears to be haploinsufficient in its ability to restore the microbiota composition profile observed in WT Long Evans rats. Lastly, Avp deletion appears to affect microbiota composition in a sexually differentiated manner.