Increasing carbohydrate availability in the hindgut promotes hypothalamic neurotransmitter synthesis: aromatic amino acids linking the microbiota-brain axis.

The gut microbiota is increasingly recognized to modulate brain function by recent studies demonstrating the central effects of various gut microbial manipulation strategies. Our previous study demonstrated that antibiotic-induced alterations of hindgut microbiota are associated with changes in aromatic amino acid (AAA) metabolism and hypothalamic neurochemistry, while the underlying mechanistic insight is limited. Given that the microbial AAA metabolism can be affected by luminal carbohydrate availability, here we hypothesize that increasing hindgut carbohydrate availability affects the expression of neurotransmitters in the porcine hypothalamus. A hindgut microbiota-targeted strategy was adopted by increasing hindgut carbohydrate availability in a cecal-cannulated piglet model. Mechanistic involvement of AAAs along the gut microbiota-brain axis was further investigated in mice and neuronal cells. Increasing carbohydrate availability by cecal starch infusion led to a decrease in hindgut AAA metabolism, and an increase in systemic AAA availability, central AAA-derived neurotransmitters (5-HT, dopamine), and neurotrophin BDNF in piglets, indicating that hindgut microbiota affect hypothalamic neurochemistry in an AAA-dependent manner. Single AAA i.p. injection in mice revealed that an increase in circulating tryptophan and tyrosine elevated their concentrations in brain and finally promoted the expressions of 5-HT, dopamine, and BDNF in a time-dependent manner. Neuronal cells treated with single AAAs in vitro further demonstrated that tryptophan and tyrosine enhanced 5-HT and dopamine synthesis, respectively, and promoted BDNF expression partly through the 5-HT1A/DRD1-CREB pathway. Our study reveals that increasing hindgut carbohydrate availability promotes hypothalamic neurotransmitter synthesis and that AAAs act as potential mediators between hindgut microbiota and brain neurochemistry.

Antibiotics-induced modulation of large intestinal microbiota altered aromatic amino acid profile and expression of neurotransmitters in the hypothalamus of piglets.

The evidence of gut microbiota-mediated modulation of brain function has been widely recognized from studies using germ-free rodents or animals with oral antibiotic-induced microbiota depletion. Since the large intestine harbors greater numbers and more diverse of microbes than in the small intestine, large intestinal microbiota may play a crucial role in the modulation of brain function. In this study, a large intestinal microbiota-targeted strategy was used to investigate the impact of large intestinal microbiota on brain function. Twelve piglets (12.08 ± 0.28 kg) fitted with a T-cannula at the distal ileum were fed a standard diet and randomly assigned to two groups (n = 6) for ileal infusion of either saline or antibiotics. After 25 days of infusion, ileal and fecal microbiota, serum amino acids and neurotransmitters, and hypothalamic transcriptomics were analyzed. While the antibiotic infusion did not change the proximal ileal microbial composition, it markedly altered the fecal microbial composition and increased aromatic amino acid (AAAs) metabolism (p < 0.05), suggesting the infusion specifically targeted large intestinal microbes. Concentrations of AAAs were likewise decreased in the blood and hypothalamus (p < 0.05) by antibiotic infusion. Antibiotic infusion further decreased concentrations of hypothalamic 5-hydroxytryptamine (5-HT) and dopamine, in line with AAAs being their precursors. An up-regulation in gene expressions of neurotransmitter transporters and synthetases was observed (q < 0.001). In conclusion, the distalileal-antibiotic infusion altered neurotransmitter expression in the porcine hypothalamus and this effect occurred simultaneously with changes in both the large intestinal microbiota, and AAAs in the large intestine, blood and hypothalamus. These findings indirectly indicate that large intestinal microbiota affects hypothalamic neurotransmitter expressions. Read the Editorial Highlight for this article on page 208.

Individual and combined effects of genistein and hesperidin supplementation on meat quality in meat-type broiler chickens.

BACKGROUND: There is growing interest in improving the production and meat quality of farm animals through dietary supplementation with phytochemical (e.g. flavonoids)-rich plants and/or their extracts. This study was conducted to analyse the supplemental effects of two purified flavonoids (genistein and hesperidin) individually and in combination on the oxidative status, sensory score and quality of breast meat in meat-type broiler chickens. RESULTS: A significant increase (P < 0.05) in meat colour (L* score) and pH was observed for the group supplemented with 20 mg kg(-1) genistein and hesperidin. Water-holding capacity was also improved significantly (P < 0.01) for all genistein- and hesperidin-treated groups, while the sensory quality of breast meat remained unaffected. Lipid oxidation of breast meat was reduced significantly (P < 0.01) at 0 and 15 days of refrigeration in a dose-dependent manner for all supplemented groups. Meanwhile, some treated groups showed improved (P < 0.05) body weight, feed/gain ratio and hot carcass weight. CONCLUSION: Genistein and hesperidin supplementation to broilers improved meat quality in a dose-dependent fashion, with pronounced effects of combined treatment. The results indicated that purified flavonoids such as genistein and hesperidin could potentially be used as feed additives in broiler production to promote meat quality.

Isoflavonic phytoestrogens--new prebiotics for farm animals: a review on research in China.

Isoflavones are recognized to be estrogenic compounds that are often associated with a reduced risk of cancers. The estrogenic activity can be enhanced after metabolization to more active compounds such as genistein and daidzein by gut microorganisms. The direct use of these metabolites has been investigated in laboratory rats and farm animals over the last decade. This paper reviews the research progress on the effect of isoflavonic compounds including metabolites on the physiology, gut microbiology and performance of farm animals in China.