MOESM1 of Effect of antibiotic pre-treatment and pathogen challenge on the intestinal microbiota in mice

Additional file 1. Additional figures

The effects of trans-resveratrol on insulin resistance, inflammation, and microbiota in men with the metabolic syndrome: A pilot randomized, placebo-controlled clinical trial

Background and Aim: The metabolic syndrome (MetS) is a pathological condition comprised of abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. It has become a major threat globally, resulting in rapidly increasing rates of diabetes, coronary heart disease, and stroke. The polyphenol resveratrol (RES) is believed to improve glucose homeostasis and insulin resistance by activating sirtuin, which acetylates and coactivates downstream targets and affects glucose and lipid homeostasis in the liver, insulin secretion in the pancreas, and glucose uptake in skeletal muscle. We studied the effects of RES on insulin resistance, glucose homeostasis, and concomitant effects on adipose tissue metabolism and fecal microbiota in insulin-resistant subjects with the MetS. Methods: A total of 28 obese men with the MetS were studied during a 35-day stay in the Rockefeller University Hospital metabolic unit. Subjects were randomized to receive RES 1 g orally twice daily or placebo while kept weight stable and consuming a western-style diet. At baseline, and after 30 days of RES or placebo administration, subjects underwent testing that included a euglycemic, hyperinsulinemic clamp, 2-h oral glucose tolerance test (GTT), resting energy expenditure, daily blood pressure monitoring, abdominal adipose tissue biopsy, and fecal and blood collections. Results: RES induced no changes in insulin resistance but reduced the 120-min time point and the area under the curve for glucose concentration in the 2-h GTT. In post-hoc analysis, Caucasian subjects showed a significant improvement in insulin sensitivity and glucose homeostasis after GTT, whereas non-Caucasians showed no similar effects. Levels of fasting plasma RES and its primary metabolite dihydroresveratrol were variable and did not explain the racial differences in glucose homeostasis. RES administration to Caucasian subjects leads to an increase in several taxa including Akkermansia muciniphila. Conclusions: RES 2 g administered orally to obese men with MetS and insulin resistance marginally altered glucose homeostasis. However, in a small group of Caucasians, insulin resistance and glucose homeostasis improved. No concomitant changes in adipose tissue metabolism occurred, but fecal microbiota showed RES-induced changes. Relevance for Patients: The MetS increases the risk of diabetes, heart disease, and stroke. A major component of the syndrome is insulin resistance, resulting in systemic inflammation and hyperinsulinemia. The primary treatment consists of lifestyle changes, improved diet, and increased physical activity. This is often unsuccessful. In this study, RES was well tolerated. In Caucasian men, it significantly improved insulin sensitivity and glucose homeostasis. Similar results were found in studies that consisted exclusively of Caucasian men. However, RES presents a novel addition to the current treatment of the MetS and its sequelae

Influence of the early-life gut microbiota on the immune responses to an inhaled allergen

Antibiotics, among the most used medications in children, affect gut microbiome communities and metabolic functions. These changes in microbiota structure can impact host immunity. We hypothesized that early-life microbiome alterations would lead to increased susceptibility to allergy and asthma. To test this, mouse pups between postnatal days 5-9 were orally exposed to water (control) or to therapeutic doses of azithromycin or amoxicillin. Later in life, these mice were sensitized and challenged with a model allergen, house dust mite (HDM), or saline. Mice with early-life azithromycin exposure that were challenged with HDM had increased IgE and IL-13 production by CD4$^{+}$ T cells compared to unexposed mice; early-life amoxicillin exposure led to fewer abnormalities. To test that the microbiota contained the immunological cues to alter IgE and cytokine production after HDM challenge, germ-free mice were gavaged with fecal samples of the antibiotic-perturbed microbiota. Gavage of adult germ-free mice did not result in altered HDM responses, however, their offspring, which acquired the antibiotic-perturbed microbiota at birth showed elevated IgE levels and CD4$^{+}$ cytokines in response to HDM, and altered airway reactivity. These studies indicate that early-life microbiota composition can heighten allergen-driven Th2/Th17 immune pathways and airway responses in an age-dependent manner