The gut-brain axis (GBA) is a bilateral communication network between the gastrointestinal (GI) tract and the central nervous system. The essential amino acid tryptophan contributes to the normal growth and health of both animals and humans and, importantly, exerts modulatory functions at multiple levels of the GBA. Tryptophan is the sole precursor of serotonin, which is a key monoamine neurotransmitter participating in the modulation of central neurotransmission and enteric physiological function. In addition, tryptophan can be metabolized into kynurenine, tryptamine, and indole, thereby modulating neuroendocrine and intestinal immune responses. The gut microbial influence on tryptophan metabolism emerges as an important driving force in modulating tryptophan metabolism. Here, we focus on the potential role of tryptophan metabolism in the modulation of brain function by the gut microbiota. We start by outlining existing knowledge on tryptophan metabolism, including serotonin synthesis and degradation pathways of the host, and summarize recent advances in demonstrating the influence of the gut microbiota on tryptophan metabolism. The latest evidence revealing those mechanisms by which the gut microbiota modulates tryptophan metabolism, with subsequent effects on brain function, is reviewed. Finally, the potential modulation of intestinal tryptophan metabolism as a therapeutic option for brain and GI functional disorders is also discussed.

SummaryA reciprocal cross-fostering model with an obese typical Chinese piglet breed and a lean Western breed was used to identify genetic and maternal effects on the acquisition and development gut bacteria from birth until after weaning. Pyrosequencing of 16S rRNA genes results revealed an age-and diet-dependent bacterial succession process in piglets. During the first 3 days after birth, the bacterial community was relatively simple and dominated by Firmicutes with 79% and 65% relative abundance for Meishan and Yorkshire piglets, respectively. During the suckling period until day 14, the piglet breed and the nursing mother lead to increasing differentiation of the fecal bacterial community, with specific bacteria taxa associated with breed, and others with the nursing sow most likely due to its milk composition. Although the effect of nursing mother and the breed were evident through the suckling period, the introduction of solid feed and subsequent weaning were the major events occurring that dominated succession of the gut microbiota in the early life of piglets. This piglet crossfostering model is a useful tool for studying the effects of diet, host genetics and the environment on the development and acquisition of the gut microbiota and over longer studies the subsequent impact on growth, health and performance of pigs.

Gut microbiota regulates intestinal and extraintestinal homeostasis. Accumulating evidence suggests that the gut microbiota may also regulate brain function and behavior. Results from animal models indicate that disturbances in the composition and functionality of some microbiota members are associated with neurophysiological disorders, strengthening the idea of a microbiota–gut–brain axis and the role of microbiota as a “peacekeeper” in the brain health. Here, we review recent discoveries on the role of the gut microbiota in central nervous system-related diseases. We also discuss the emerging concept of the bidirectional regulation by the circadian rhythm and gut microbiota, and the potential role of the epigenetic regulation in neuronal cell function. Microbiome studies are also highlighted as crucial in the development of targeted therapies for neurodevelopmental disorders.

Early-life antibiotic interventions can change the predisposition to disease by disturbing the gut microbiota. However, the impact of antibiotics on gut microbiota in the gastrointestinal tract is not completely understood, although antibiotic-induced alterations in the distal gut have been reported. Here, employing a piglet model, the microbial composition was analyzed by high-throughput 16S rRNA gene sequencing and PICRUSt predictions of metagenome function. The present study showed clear spatial variation of microbial communities in the stomach and intestine, and found that the administration of antibiotics (a mixture of olaquindox, oxytetracycline calcium, kitasamycin) in early life caused markedly differential alterations in the compartmentalized microbiota, with major alterations in their spatial variation in the lumen of the stomach and small intestine. In piglets fed an antibiotic-free diet, most of the variation in microbial communities was concentrated in gut segments and niches (lumen/mucosa). The microbial diversity was higher in the lumen of stomach and duodenum than that in ileum. The early-life antibiotic intervention decreased the abundance of some Lactobacillus species and increased the abundance of potentially pathogenic Streptococcus suis in the lumen of the stomach and small intestine. Interestingly, the intervention increased the abundance of Treponema only in the colonic lumen and that of Faecalibacterium only in the ileal mucosa. Furthermore, the antibiotic intervention exerted location-specific effects on the functional potential involved in the phosphotransferase system (decreased sucrose phosphotransferase in the stomach) and antibiotic-resistance genes (increased in the colon). These results point to an early-life antibiotic-induced dramatic and location-specific shift in the gut microbiota, with profound impact in the foregut and less impact in the hindgut. Collectively, these findings provide new insights into the membership of the microbiota along the gastrointestinal tract of piglets and highlight the importance of considering the foregut microbiota in health management of piglets at early life.

Our findings suggest that the HPD altered the colonic microbial community, shifted the metabolic profile, and affected the host response in the colons of rats toward an increased risk of colonic disease.

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.

Backgroud: This study aimed to determine the effects of early antibiotic intervention (EAI) on subsequent blood parameters, apparent nutrient digestibility, and fecal fermentation profile in pigs with different dietary crude protein (CP) levels. Eighteen litters of piglets (total 212) were randomly allocated to 2 groups and were fed a creep feed diet with or without in-feed antibiotics (olaquindox, oxytetracycline calcium and kitasamycin) from postnatal d 7 to d 42. On d 42, the piglets within the control or antibiotic group were mixed, respectively, and then further randomly assigned to a normal- ( Results: EAI increased (P < 0.05) albumin and glucose concentrations in low-CP diet on d 77, and increased (P < 0.05) urea concentration in normal-CP diet. On d 185, EAI increased (P < 0.05) globulin concentration in normal-CP diets, but decreased glucose concentration. For nutrient digestibility, EAI increased (P < 0.05) digestibility of CP on d 77. For fecal microbiota, the EAI as well as low-CP diet decreased (P < 0.05) E. coli count on d 77. For fecal metabolites, on d 77, EAI decreased (P < 0.05) total amines concentration but increased skatole concentration in low-CP diet. On d 185, the EAI increased (P < 0.05) putrescine and total amines concentrations in low-CP diets but reduced (P < 0.05) in the normal-CP diets. The low-CP diet decreased the concentrations of these compounds. Conclusions: Collectively, these results indicate that EAI has short-term effects on the blood parameters and fecal microbial fermentation profile. The effects of EAI varied between CP levels, which was characterized by the significant alteration of glucose and putrescine concentration.

In modern swine husbandry systems, antibiotics have been used as growth promoters for piglets during suckling or weaning period. However, while early colonization of intestinal microbiota has been regarded crucial for the host’s later life performance and well-being, little is known about the impact of antibiotics on intestinal microbiota in suckling piglets. The present study aimed to investigate the effects of early antibiotics exposure on gut microbiota and microbial metabolism of suckling piglets. Sixteen litters of suckling piglets were fed a creep feed diet with (Antibiotic) or without (Control) antibiotics from postnatal days 7–23 (n = 8). The ileal and cecal digesta were obtained for microbial composition and microbial metabolites analysis. The results showed that the antibiotics significantly altered the bacterial community composition by decreasing (P < 0.05) the diversity and richness in the ileum. The antibiotics significantly reduced the abundance of Lactobacillus in both the ileum and cecum, increased the abundance of Streptococcus, unclassified Enterococcaceae, unclassified Fusobacteriales, and Corynebacterium in the ileum, and the abundance of unclassified Ruminococcaceae and unclassified Erysipelotrichaceae in the cecum. The antibiotics decreased (P < 0.05) ileal lactate concentration and cecal concentration of total short-chain fatty acids (SCFAs). But the antibiotics enhanced protein fermentation (P < 0.05) in the ileum and cecum, as ileal concentrations of putrescine and cadaverine, and cecal concentrations of isobutyrate, isovalerate, putrescine, cadaverine, spermine, and spermidine were significantly increased (P < 0.05). These results indicated that early antibiotics exposure significantly altered the microbial composition of suckling piglets toward a vulnerable and unhealthy gut environment. The findings provide a new insight on the antibiotics impact on neonates and may provide new framework for designing alternatives to the antibiotics toward a healthy practice for suckling piglets.