Gallnut Tannic Acid Exerts Anti-stress Effects on Stress-Induced Inflammatory Response, Dysbiotic Gut Microbiota, and Alterations of Serum Metabolic Profile in Beagle Dogs

Stress exposure is a potential threat to humans who live or work in extreme environments, often leading to oxidative stress, inflammatory response, intestinal dysbiosis, and metabolic disorders. Gallnut tannic acid (TA), a naturally occurring polyphenolic compound, has become a compelling source due to its favorable anti-diarrheal, anti-oxidative, anti-inflammatory, and anti-microbial activities. Thus, this study aimed to evaluate the anti-stress effects of gallnut TA on the stress-induced inflammatory response, dysbiotic gut microbiota, and alterations of serum metabolic profile using beagle models. A total of 13 beagle dogs were randomly divided into the stress (ST) and ST + TA groups. Dietary supplementation with TA at 2.5 g/kg was individually fed to each dog in the ST + TA group for 14 consecutive days. On day 7, all dogs were transported for 3 h from a stressful environment (days 1-7) to a livable site (days 8-14). In our results, TA relieved environmental stress-induced diarrheal symptoms in dogs and were shown to protect from myocardial injury and help improve immunity by serum biochemistry and hematology analysis. Also, TA inhibited the secretion of serum hormones [cortisol (COR), glucocorticoid (GC), and adrenocorticotropic hormone (ACTH)] and the expression of heat shock protein (HSP) 70 to protect dogs from stress-induced injury, thereby relieving oxidative stress and inflammatory response. Fecal 16S rRNA gene sequencing revealed that TA stimulated the growth of beneficial bacteria (Allobaculum, Dubosiella, Coriobacteriaceae_UCG-002, and Faecalibaculum) and suppressed the growth of pathogenic bacteria (Escherichia-Shigella and Streptococcus), thereby increasing fecal butyrate levels. Serum metabolomics further showed that phytosphingosine, indoleacetic acid, arachidonic acid, and biotin, related to the metabolism of sphingolipid, tryptophan, arachidonic acid, and biotin, respectively, could serve as potential biomarkers of stress exposure. Furthermore, Spearman's correlation analysis showed strong relationships between the four potential serum biomarkers and differential bacteria. Overall, gallnut TA may be a potential prebiotic for the prevention and treatment of stress-induced metabolic disorders by targeting intestinal microbiota.