Synergistic effects of exercise and catalase overexpression on gut microbiome.

Exercise influences metabolic parameters in part by modulating redox stress and as recently suggested, by affecting the gut microbiome. However, whether excess endogenous antioxidant potentiates or interferes with the beneficial effects of exercise on the gut microbiome is not known. A comparison of the gut microbiome of C57Bl6 (C57/WT) mice to the 'stress-less' catalase overexpressing mice models ([Tg(CAT)± ] and Bob-Cat), that were either exercised or remained sedentary, showed differences in both alpha and beta diversity. The significant variation was explained by genotypes along with exercise, suggesting a synergistic relationship between exercise and genotypic traits. Linear discriminant analysis effect size (LEfSe) analysis also revealed differential taxa within the exercised/genotype cohorts in contrast to those within sedentary/genotype cohorts. Functional pathway predictions from PICRUSt2 showed enrichment for the metabolism of short-chain fatty acids, butanoate and propanoate pathways in exercised groups. Spearman correlations between enriched taxa and metabolic parameters showed correlations with body or fat weight in some of the cohorts. However, there were significant correlations of differential taxa among all cohorts against parameters that predict energy metabolism, such as respiratory exchange ratio and energy expenditure. Overall, our study showed that there was a synergistic beneficial influence of antioxidant overexpression and exercise on the gut microbiome.

Excess Dietary Zinc Intake in Neonatal Mice Causes Oxidative Stress and Alters Intestinal Host-Microbe Interactions.

SCOPE: Greater than 68% of young infants are exposed to dietary zinc (Zn) levels that are higher than the Tolerable Upper Intake Limit. However, the consequences of excess dietary Zn during early life on intestinal function and host-microbe interactions are unknown. METHODS AND RESULTS: Neonatal mice are gavaged with 100 Zn µg d-1 from postnatal day (PN) 2 through PN10 and indices of intestinal function and host-microbe interactions are compared to unsupplemented mice. Excess dietary Zn causes oxidative stress, increases goblet cell number and mucus production, and are associated with increased intestinal permeability and systemic inflammation. Over 900 genes are differentially expressed; 413 genes display a fold-change >1.60. The Gene Ontology Biological processes most significantly affected include biological adhesion, the immune system, metabolic processes, and response to stimulus. Key genes most highly and significantly upregulated include ALDH2, MT1, TMEM6, CDK20, and COX62b, while CALU, ST3GAL4, CRTC2, SLC28A2, and COMMA1 are downregulated. These changes are associated with a microbiome enriched in pathogenic taxa including Pseudomonadales and Campylobacter, and greater expression of bacterial stress response genes. CONCLUSION: Excess dietary Zn may have unforeseen influences on epithelial signaling pathways, barrier function, and luminal ecology in the intestine that may have long-term consequences on intestinal health.

Tree Nut Consumption and Adipose Tissue Mass: Mechanisms of Action.

There is concern that tree nuts may cause weight gain due to their energy density, yet evidence shows that tree nuts do not adversely affect weight status. Epidemiologic and experimental studies have shown a reduced risk of chronic diseases with tree nut consumption without an increased risk of weight gain. In fact, tree nuts may protect against weight gain and benefit weight-loss interventions. However, the relation between tree nut consumption and adiposity is not well understood at the mechanistic level. This review summarizes the proposed underlying mechanisms that might account for this relation. Evidence suggests that tree nuts may affect adiposity through appetite control, displacement of unfavorable nutrients, increased diet-induced thermogenesis, availability of metabolizable energy, antiobesity action of bioactive compounds, and improved functionality of the gut microbiome. The gut microbiome is a common factor among these mechanisms and may mediate, in part, the relation between tree nut consumption and reduced adiposity. Further research is needed to understand the impact of tree nuts on the gut microbiome and how the gut microbial environment affects the nutrient absorption and metabolism of tree nuts. The evidence to date suggests that tree nut consumption favorably affects body composition through different mechanisms that involve the gut microbiome. A better understanding of these mechanisms will contribute to the evolving science base that addresses the causes and treatments for overweight and obesity.

NOD2 Genetic Variants Predispose One of Two Familial Adenomatous Polyposis Siblings to Pouchitis Through Microbiome Dysbiosis.

BACKGROUND AND AIMS: Individuals with familial adenomatous polyposis (FAP) may undergo a total proctocolectomy with ileal pouch-anal anastomosis (IPAA) to surgically treat their disease. Inflammation of the ileal pouch, termed pouchitis, is uncommon in FAP patients but prevalent in patients who received IPAA for ulcerative colitis, a type of inflammatory bowel disease (IBD). METHODS AND RESULTS: We report on two FAP siblings, living in the same household, who underwent IPAA surgery within one week of each other. Their mother also had an IPAA for FAP. One sibling developed pouchitis while his brother and mother have remained pouchitis-free. We investigated the genetic and microbial factors that might explain the development of pouchitis in the one sibling. We surveyed DNA isolated from the two brothers and their parents for NOD2 IBD risk variants by Sanger sequencing. The composition of mucosa-associated bacteria was analyzed by 16S rRNA gene sequencing on terminal ileum and rectal tissue collected at the time of surgical resection from the two brothers. The sibling with pouchitis inherited the IBD-associated risk alleles for NOD2 (rs17221417 and rs2076756) from his healthy father. Both the mother and unaffected brother lacked these variants. Microbiome sequencing of the terminal ileum and rectum found reduced levels of potentially 'beneficial' bacteria (Faecalibacterium prausnitzii, Bacteroides, and Ruminococcaceae) in the sibling with pouchitis relative to his brother. CONCLUSION: These findings suggest that the NOD2 signaling pathway may contribute to intrinsic bacterial dysbiosis which is pre-existing and which may then predispose individuals to pouchitis after IPAA surgery.