A synthetic formula amino acid diet leads to microbiome dysbiosis, reduced colon length, inflammation, and altered locomoter
activity in C57BL/6J mice
Mancilla, V.J., Braden-Kuhle, P.N., Brice, K.N.,
Mann, A.E., Williams, M.T., Zhang, Y., Chumley, M.J., Barber, R.C., White, S.N., Boehm, G.W., and
Allen, M.S.
Although a typical treatment option for metabolic disorders is synthetically derived formula diets, the effects have not
been extensively studied, and may render other health consequences. Dietary fiber is essential to protect the gut from opportunistic
pathogens and increase the population of commensal bacteria in the colon, which is the most densely populated area for microbiota in
the human body. Previous research has demonstrated that diets high in fiber are crucial to human health, as they increase microbial
diversity and short chain fatty acid production and allow for proper maintenance of gut tissue. Notably, evidence suggests that
high-fiber diets improve cognition and provide neuroprotection, as the gut and brain are connected by the gut-brain axis. Conversely,
previous studies in both human subjects and animals have shown that low-fiber diets are associated with decreased gut bacterial
diversity, decreased short chain fatty acid production, increased gastrointestinal distress, and increased cognitive dysfunction and
anxiety-like behavior. In the current, multidisciplinary study, we examined the effects of a synthetically derived, low-fiber, amino
acid diet on anxiety-like behavior, locomotor activity, cognition, the gut microbiome, cytokines, colon length, and short-chain fatty
acid production in male C57BL/6J mice. Mice were assigned to one of two diet conditions at post-natal day 21: a standard rodent diet
or a synthetic diet analogous to the standard rodent diet, and continued consumption for 13 weeks. The results revealed that this
synthetic diet altered locomotor activity. Additionally, by sequencing the 16S rRNA gene from fecal samples (collected weekly) in each
group, we identified a decrease in bacterial diversity, and through PICRUSt2 analysis, we predicted changes in metabolic pathway
activities. Furthermore, we saw a decrease in the production of short chain fatty acids and a shortening of the colon in mice
consuming the synthetic diet. Finally, we measured TNF-α, IL-6, and IL-10 in serum, the hippocampus, and colon, and found that the
synthetic diet significantly increased IL-6 production in the hippocampus. These results demonstrate the importance of a
multidisciplinary approach to future diet and microbiome studies, as diet not only impacts the gut microbiome, but potentially
cognitive and immune function as well.