The Microbiota-Gut-Brain Axis: Clinical Applications in Obesity and Type 2 Diabetes.

Abstract: Recent investigations highlight the importance of the gut microbiota and bacteria-derived metabolites as key components in obesity and metabolic health. The microbiota-gut-brain axis presents promising targets for future obesity treatments and prevention. However, the current state of evidence and existing clinical applications of the microbiota-gut-brain axis have yet to be summarized in a thorough review. Therefore, we sought to examine current evidence on the effect of lifestyle, dietary, pharmacological, and surgical interventions on the microbiota-gut-brain axis. In addition, this review highlights potential next steps in research toward characterizing the role of the microbiota-gut-brain axis in metabolic health, along with possible interventions to address obesity.

The Microbiota-Gut-Brain Axis: Clinical Applications in Obesity and Type 2 Diabetes

ABSTRACT Recent investigations highlight the importance of the gut microbiota and bacteria-derived metabolites as key components in obesity and metabolic health. The microbiota-gut-brain axis presents promising targets for future obesity treatments and prevention. However, the current state of evidence and existing clinical applications of the microbiota-gut-brain axis have yet to be summarized in a thorough review. Therefore, we sought to examine current evidence on the effect of lifestyle, dietary, pharmacological, and surgical interventions on the microbiota-gut-brain axis. In addition, this review highlights potential next steps in research toward characterizing the role of the microbiota-gut-brain axis in metabolic health, along with possible interventions to address obesity.

Weight Loss Strategies.

Lifestyle interventions for weight loss combine support for changing diet and physical activity with weight management education and are considered the first line treatment for obesity. A variety of diet-focused interventions including time-restricted eating are also increasingly being promoted for weight management. This chapter reviews different types of interventions for weight management, their underlying health behavior change models, and effectiveness to date in randomized trials. The results justify increasing efforts to improve program effectiveness generally, and to personalize interventions to support long-term adherence. The high prevalence of obesity worldwide, combined with the known increase in risk of non-communicable diseases with duration of excess weight, provides a compelling justification for routine delivery of effective weight management interventions in the community and in clinical care.

A Novel Combination of Fruits and Vegetables Prevents Diet-Induced Hepatic Steatosis and Metabolic Dysfunction in Mice.

BACKGROUND: Epidemiological studies suggest that higher fruits and vegetables (F&V) consumption correlates with reduced risk of hepatic steatosis, yet evidence for causality and the underlying mechanisms is lacking. OBJECTIVES: We aimed to determine the causal relation between F&V consumption and improved metabolic disorders in mice fed high-fat (HF) (Experiment-1) or normal-fat (Experiment-2) diets and its underlying mechanisms. METHODS: Six-week-old male C57BL/6J mice were randomly grouped and fed diets supplemented at 0%-15% (wt:wt) with a freeze-dried powder composed of 24 commonly consumed F&V (human equivalent of 0-9 servings/d) for 20 wk. In Experiment-1, mice were fed an HF (45% kcal fat) diet with 0% (HF0), 5%, 10%, or 15% (HF15) F&V or a matched low-fat control diet (10% kcal fat). In Experiment-2, mice were fed an AIN-93 diet (basal) (B, 16% kcal fat) with 0% (B0), 5%, 10%, or 15% (B15) F&V supplementation. Body weight and composition, food intake, hepatic steatosis, inflammation, ceramide levels, sphingomyelinase activity, and gut microbiota were assessed. RESULTS: In Experiment-1, mice fed the HF15 diet had lower weight gain (17.9%), hepatic steatosis (48.4%), adipose tissue inflammation, blood (24.6%) and liver (33.9%) ceramide concentrations, and sphingomyelinase activity (38.8%) than HF0 mice (P < 0.05 for all). In Experiment-2, mice fed the B15 diet had no significant changes in weight gain but showed less hepatic steatosis (28.5%), blood and adipose tissue inflammation, and lower blood (30.0%) ceramide concentrations than B0 mice (P < 0.05 for all). These F&V effects were associated with favorable microbiota changes. CONCLUSIONS: These findings represent the first evidence for a causal role of high F&V intake in mitigating hepatic steatosis in mice. These beneficial effects may be mediated through changes in ceramide and/or gut microbiota, and suggest that higher than currently recommended servings of F&V may be needed to achieve maximum health benefits.

Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Zinc is essential for the regulation of immune response. T cell function declines with age. Zinc supplementation has the potential to improve the serum zinc concentrations and immunity of nursing home elderly with a low serum zinc concentration. OBJECTIVE: We aimed to determine the effect of supplementation with 30 mg Zn/d for 3 mo on serum zinc concentrations of zinc-deficient nursing home elderly. DESIGN: This was a randomized, double-blind, placebo-controlled study. Of 53 nursing home elderly (aged ≥65 y) who met eligibility criteria, 58% had a low serum zinc concentration (serum zinc <70 µg/dL); these 31 were randomly assigned to zinc (30 mg Zn/d) (n = 16) or placebo (5 mg Zn/d) (n = 15) groups. The primary outcome measure was change in serum zinc concentrations between baseline and month 3. We also explored the effects of supplementation on immune response. RESULTS: Baseline characteristics were similar in the 2 groups. The difference in the mean change in serum zinc was significantly higher, by 16%, in the zinc group than in the placebo group (P = 0.007) when baseline zinc concentrations were controlled for. In addition, controlling for baseline C-reactive protein, copper, or albumin did not change the results. However, supplementation of participants with ≤60 µg serum Zn/dL failed to increase their serum zinc to ≥70 µg/dL. Zinc supplementation also significantly increased anti-CD3/CD28 and phytohemagglutinin-stimulated T cell proliferation, and the number of peripheral T cells (P < 0.05). When proliferation was expressed per number of T cells, the significant differences between groups were lost, suggesting that the zinc-induced enhancement of T cell proliferation was mainly due to an increase in the number of T cells. CONCLUSIONS: Zinc supplementation at 30 mg/d for 3 mo is effective in increasing serum zinc concentrations in nursing home elderly; however, not all zinc-deficient elderly reached adequate concentrations. The increase in serum zinc concentration was associated with the enhancement of T cell function mainly because of an increase in the number of T cells.