The molecular signaling of exercise and obesity in the microbiota-gut-brain axis.

Obesity is one of the major pandemics of the 21st century. Due to its multifactorial etiology, its treatment requires several actions, including dietary intervention and physical exercise. Excessive fat accumulation leads to several health problems involving alteration in the gut-microbiota-brain axis. This axis is characterized by multiple biological systems generating a network that allows bidirectional communication between intestinal bacteria and brain. This mutual communication maintains the homeostasis of the gastrointestinal, central nervous and microbial systems of animals. Moreover, this axis involves inflammatory, neural, and endocrine mechanisms, contributes to obesity pathogenesis. The axis also acts in appetite and satiety control and synthesizing hormones that participate in gastrointestinal functions. Exercise is a nonpharmacologic agent commonly used to prevent and treat obesity and other chronic degenerative diseases. Besides increasing energy expenditure, exercise induces the synthesis and liberation of several muscle-derived myokines and neuroendocrine peptides such as neuropeptide Y, peptide YY, ghrelin, and leptin, which act directly on the gut-microbiota-brain axis. Thus, exercise may serve as a rebalancing agent of the gut-microbiota-brain axis under the stimulus of chronic low-grade inflammation induced by obesity. So far, there is little evidence of modification of the gut-brain axis as a whole, and this narrative review aims to address the molecular pathways through which exercise may act in the context of disorders of the gut-brain axis due to obesity.

The Emerging Role of the Aging Process and Exercise Training on the Crosstalk between Gut Microbiota and Telomere Length.

Aging is a natural process of organism deterioration, which possibly impairs multiple physiological functions. These harmful effects are linked to an accumulation of somatic mutations, oxidative stress, low-grade inflammation, protein damage, and mitochondrial dysfunction. It is known that these factors are capable of inducing telomere shortening, as well as intestinal dysbiosis. Otherwise, among the biological mechanisms triggered by physical exercise, the attenuation of pro-inflammatory mediators accompanied by redox state improvement can be the main mediators for microbiota homeostasis and telomere wear prevention. Thus, this review highlights how oxidative stress, inflammation, telomere attrition, and gut microbiota (GM) dysbiosis are interconnected. Above all, we provide a logical foundation for unraveling the role of physical exercise in this process. Based on the studies summarized in this article, exercise training can increase the biodiversity of beneficial microbial species, decrease low-grade inflammation and improve oxidative metabolism, these factors together possibly reduce telomeric shortening.

Is There an Exercise-Intensity Threshold Capable of Avoiding the Leaky Gut?

Endurance-sport athletes have a high incidence of gastrointestinal disorders, compromising performance and impacting overall health status. An increase in several proinflammatory cytokines and proteins (LPS, I-FABP, IL-6, IL-1ß, TNF-α, IFN-γ, C-reactive protein) has been observed in ultramarathoners and triathlon athletes. One of the most common effects of this type of physical activity is the increase in intestinal permeability, known as leaky gut. The intestinal mucosa's degradation can be identified and analyzed by a series of molecular biomarkers, including the lactulose/rhamnose ratio, occludin and claudin (tight junctions), lipopolysaccharides, and I-FABP. Identifying the molecular mechanisms involved in the induction of leaky gut by physical exercise can assist in the determination of safe exercise thresholds for the preservation of the gastrointestinal tract. It was recently shown that 60 min of vigorous endurance training at 70% of the maximum work capacity led to the characteristic responses of leaky gut. It is believed that other factors may contribute to this effect, such as altitude, environmental temperature, fluid restriction, age and trainability. On the other hand, moderate physical training and dietary interventions such as probiotics and prebiotics can improve intestinal health and gut microbiota composition. This review seeks to discuss the molecular mechanisms involved in the intestinal mucosa's adaptation and response to exercise and discuss the role of the intestinal microbiota in mitigating these effects.

An overview of the level of dietary support in the gut microbiota at different stages of life: A systematic review.

BACKGROUND & AIMS: The gut microbiome is an essential factor for the health of the host. Several factors may alter the gut's microbiota composition, including genetic factors, lifestyle, aging, and dietary intervention. This process can be an essential element in the prevention and treatment of diseases associated with microbiome dysfunction through appropriate dietary interventions. Based on this context, a systematic review was carried out in order to assess the effect of dietary intervention on the profile of the gut microbiota throughout different stages of life. METHODS: The systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA), with the eligibility criteria following the principle of PICOS. The literature search was carried out in 2019 throughout PubMed/MEDLINE, Scopus, and Science Direct. Thus, 1237 studies were selected, and 40 articles were included by criteria. RESULTS: According to the level of evidence of Centre for Evidence-Based Medicine (OCEBM), 21 studies reached the level of evidence B1, 15 articles were classified with B2, and four articles with B3. No dietary intervention was applied at all stages of life, nor with similar proportions of intervention. No dietary intervention was applied at all stages of life, nor with similar proportions of intervention. On the other hand, dietary interventions alter the intestinal microbiota in different pathological realities. CONCLUSIONS: Different dietary interventions change the microbiome composition at all stages of life in healthy and pathological individuals. However, more clinical studies are needed to identify the specifics of each stage in response to interventions.

Limited Effects of Low-to-Moderate Aerobic Exercise on the Gut Microbiota of Mice Subjected to a High-Fat Diet.

Several studies have indicated that diet and exercise may modulate the gut microbiota in obese subjects. Both interventions were shown to alter the microbiota orthogonally. However, this relationship has not been fully explored. This study analyzed the effects of low-to-moderate aerobic training on the fecal microbiota of mice subjected to a high-fat diet (HFD). Here, 40 male mice (C57Bl/6) were divided into two groups with standard diet (SD; 12.4% lipid) and HFD (60.3% lipid) for four months. These groups were divided into four, named SD control, HF control, SD trained and HF trained. All animals were submitted to an incremental test to estimate low-to-moderate maximum speed. Training consisted of 30 min·day-1, 5 days/week, for 8 weeks. The HFD increased the body weight (p < 0.0001) and adiposity index (p < 0.05). HFD also negatively influenced performance in exercise training. Moreover, the diversity of gut microbiota was reduced by the HFD in all groups. A low-to-moderate exercise was ineffective in modulating the gut microbiota composition in mice subjected to HFD. These findings suggest that two months of low-to-moderate exercise does not achieve a preponderant modulatory effect on shaping microbiota when submitted to the high-fat diet.

Experimental Evidence for Azeotrope Formation from Protic Ionic Liquids.

Herein, we present experimental evidence that protic ionic liquids (PILs), derived from 1 : 1 liquid mixtures of the organic superbases 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) with carboxylic acids, form azeotropic mixtures with acid/base molar fractions different from 1 : 1. The ability of the carboxylic acids to form strong hydrogen bonds with the PIL ion pair leads to an azeotropic composition richer in the acid component. The results show that the azeotropic composition is ruled by the extent of acid-base equilibrium and the relative volatility of the neutral species in the PIL medium. The PILs show marked negative deviations from Raoult's Law with the stronger superbase (DBU) leading to an azeotropic composition closer to the equimolar 1 : 1 ratio.

Vaporization of protic ionic liquids derived from organic superbases and short carboxylic acids.

This work presents a comprehensive evaluation of the phase behaviour and cohesive enthalpy of protic ionic liquids (PILs) composed of 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) organic superbases with short-chain length (acetic, propionic and butyric) carboxylic acids. Glass transition temperatures, Tg, and enthalpies of vaporization, ΔHvap, were measured for six [BH][A] (1 : 1) PILs (B = DBN, DBU; A = MeCOO, EtCOO, nPrCOO), revealing more significant changes upon increasing the number of -CH2- groups in the base than in the acid. The magnitude of ΔHvap evidences that liquid PILs have a high proportion of ions, although the results also indicate that in DBN PILs the concentration of neutral species is not negligible. In the gas phase, these PILs exist as a distribution of ion pairs and isolated neutral species, with speciation being dependent on the temperature and pressure conditions - at high temperatures and low pressures the separated neutral species dominate. The higher Tg and ΔHvap of the DBU PILs are explained by the stronger basicity of DBU (as supported by NMR and computational calculations), which increases the extent of proton exchange and the ionic character of the corresponding PILs, resulting in stronger intermolecular interactions in condensed phases.

The Effects of Acute and Chronic Exercise on Skeletal Muscle Proteome.

Skeletal muscle plasticity and its adaptation to exercise is a topic that is widely discussed and investigated due to its primary role in the field of exercise performance and health promotion. Repetitive muscle contraction through exercise stimuli leads to improved cardiovascular output and the regulation of endothelial dysfunction and metabolic disorders such as insulin resistance and obesity. Considerable improvements in proteomic tools and data analysis have broth some new perspectives in the study of the molecular mechanisms underlying skeletal muscle adaptation in response to physical activity. In this sense, this review updates the main relevant studies concerning muscle proteome adaptation to acute and chronic exercise, from aerobic to resistance training, as well as the proteomic profile of natural inbred high running capacity animal models. Also, some promising prospects in the muscle secretome field are presented, in order to better understand the role of physical activity in the release of extracellular microvesicles and myokines activity. Thus, the present review aims to update the fast-growing exercise-proteomic scenario, leading to some new perspectives about the molecular events under skeletal muscle plasticity in response to physical activity. J. Cell. Physiol. 232: 257-269, 2017. © 2016 Wiley Periodicals, Inc.