The impact of dietary vitamin B6 deficiency on intestinal morphology, microbial profile, and gut-mediated brain function and behavior in rats

Sathya Amarasena
PhD Student
Department of Biochemistry

Date: January 29, 2024
Time: 1:00 p.m. to 2:00 p.m. 
Room: CSF 1302

Abstract:

Vitamin B6 is crucial for several metabolic pathways, including energy metabolism, cell signaling, and neurotransmitter biosynthesis. The intestinal microbiota also influences the production of gut-derived neuroactive compounds. Previous research has shown that B6 deficiency alters gut microbiota and gut metabolites. However, the impact of B6 deficiency on the gut-mediated regulation of brain function is poorly understood. We hypothesize that B6 deficiency-induced alteration of the gut microbiome can modulate brain function and host behavior by altering gut-controlled neurotransmitter synthesis and kynurenine metabolites. Sixty-four Sprague-Dawley rats (32F, 32M) were fed either an AIN-93G-based control (B6 7 mg/kg diet) or a vitamin B6 deficient (B6 0.07 mg/kg diet) diet for six weeks. Half of the animals received a cocktail of antibiotics through drinking water and weekly gavage in each diet group, while the other half received regular water. During the 6^th week, rats were subjected to behavioral experiments. The cecal microbiome was profiled using 16s rRNA full-length amplicon sequencing (PacBio Sequel 2-long read, V1-V9). The sequence data were analyzed using QIIME2 to visualize the relative abundance of bacterial taxa in each group. The small intestinal and colon morphology were histologically assessed to investigate the B6 deficiency-induced morphological changes in the gut. Data were analyzed using SPSS and 2-way ANOVA.

Microbiome analysis showed an altered relative taxonomic abundance among the treatment groups. Significant differences were observed in jejunal villous height (p=0.002), crypt depth (p=0.001), villous height/crypt depth ratio (p=0.005), and thickness of muscularis externa (P=0.005). Only crypt width (p=0.039) was significantly altered in the colon. The open field maze experiment showed that both the distance traveled (p<0.0001) and rearing time (p=0.0351) were lower in microbiota-depleted (MD), B6-deficient rats compared to the other groups. Similarly, in the elevated plus maze, MD-B6 deficient rats, specifically the females, exhibited significantly lower head dips (p=0.028) than the other rats. Also, B6-deficient male rats showed a significantly higher number of entries to the closed arm (p=0.017). The sucrose preference test showed that MD-B6 optimum female rats had the lowest preference over 24 hours (p=0.0183).

The microbiota-depleted, B6-deficient conditions can affect intestinal morphology and bacterial diversity while showing anxiety-like behavior in rats. However, future metabolome analyses are required to unravel the underlying mechanisms. Our study suggests that dietary vitamin B6 deficiency regulates host behavior through the microbiota-gut-brain axis.