Physical Activity Differentially Affects the Cecal Microbiota of Ovariectomized Female Rats Selectively Bred for High and Low Aerobic Capacity

The gut microbiota is considered a relevant factor in obesity and associated metabolic diseases, for which postmenopausal women are particularly at risk. Increasing physical activity has been recognized as an efficacious approach to prevent or treat obesity, yet the impact of physical activity on the microbiota remains under-investigated. We examined the impacts of voluntary exercise on host metabolism and gut microbiota in ovariectomized (OVX) high capacity (HCR) and low capacity running (LCR) rats. HCR and LCR rats (age = 27wk) were OVX and fed a high-fat diet (45% kcal fat) ad libitum and housed in cages equipped with (exercise, EX) or without (sedentary, SED) running wheels for 11wk (n = 7-8/group). We hypothesized that increased physical activity would hinder weight gain, increase metabolic health and shift the microbiota of LCR rats, resulting in populations more similar to that of HCR rats. Animals were compared for characteristic metabolic parameters including body composition, lipid profile and energy expenditure; whereas cecal digesta were collected for DNA extraction. 16S rRNA gene-based amplicon Illumina MiSeq sequencing was performed, followed by analysis using QIIME 1.8.0 to assess cecal microbiota. Voluntary exercise decreased body and fat mass, and normalized fasting NEFA concentrations of LCR rats, despite only running one-third the distance of HCR rats. Exercise, however, increased food intake, weight gain and fat mass of HCR rats. Exercise clustered the gut microbial community of LCR rats, which separated them from the other groups. Assessments of specific taxa revealed significant (p<0.05) line by exercise interactions including shifts in the abundances of Firmicutes, Proteobacteria, and Cyanobacteria. Relative abundance of Christensenellaceae family was higher (p = 0.026) in HCR than LCR rats, and positively correlated (p<0.05) with food intake, body weight and running distance. These findings demonstrate that exercise differentially impacts host metabolism and gut microbial communities of female HCR and LCR rats without ovarian function.     

Chemically Defined Diet Alters the Protective Properties of Fructo-Oligosaccharides and Isomalto-Oligosaccharides in HLA-B27 Transgenic Rats

Non-digestible oligosaccharides (NDO) were shown to reduce inflammation in experimental colitis, but it remains unclear whether microbiota changes mediate their colitis-modulating effects. This study assessed intestinal microbiota and intestinal inflammation after feeding chemically defined AIN-76A or rat chow diets, with or without supplementation with 8 g/kg body weight of fructo-oligosaccharides (FOS) or isomalto-oligosaccharides (IMO). The study used HLA-B27 transgenic rats, a validated model of inflammatory bowel disease (IBD), in a factorial design with 6 treatment groups. Intestinal inflammation and intestinal microbiota were analysed after 12 weeks of treatment. FOS and IMO reduced colitis in animals fed rat chow, but exhibited no anti-inflammatory effect when added to AIN-76A diets. Both NDO induced specific but divergent microbiota changes. Bifidobacteria and Enterobacteriaceae were stimulated by FOS, whereas copy numbers of Clostridium cluster IV were decreased. In addition, higher concentrations of total short-chain fatty acids (SCFA) were observed in cecal contents of rats on rat chow compared to the chemically defined diet. AIN-76A increased the relative proportions of propionate, iso-butyrate, valerate and iso-valerate irrespective of the oligosaccharide treatment. The SCFA composition, particularly the relative concentration of iso-butyrate, valerate and iso-valerate, was associated (P≤0.004 and r≥0.4) with increased colitis and IL-1 β concentration of the cecal mucosa. This study demonstrated that the protective effects of fibres on colitis development depend on the diet. Although diets modified specific cecal microbiota, our study indicates that these changes were not associated with colitis reduction. Intestinal inflammation was positively correlated to protein fermentation and negatively correlated with carbohydrate fermentation in the large intestine.     

Effects of long-term antibiotic treatment on mice urinary aromatic amino acid profiles

The gut microbiota–host co-metabolites are good indicators for representing the cross-talk between host and gut microbiota in a bi-direct manner. There is increasing evidence that levels of aromatic amino acids (AAAs) are associated with the alteration of intestinal microbial community though the effects of long-term microbial disturbance remain unclear. Here we monitored the gut microbiota composition and host–microbiota co-metabolites AAA profiles of mice after gentamicin and ceftriaxone treatments for nearly 4 months since their weaning to reveal the relationship between host and microbiome in long- term microbial disturbances. The study was performed employing targeted LC-MS measurement of AAA-related metabolites and 16S RNA sequence of mice cecal contents. The results showed obvious decreased gut microbial diversity and decreased Firmicutes/Bacteroidetes ratio in the cecal contents after long-term antibiotics treatment. The accumulated AAA (tyrosine, phenylalanine and tryptophan) and re-distribution of their downstreaming metabolites that produced under the existence of intestinal flora were found in mice treated with antibiotics for 4 months. Our results suggested that the long-term antibiotic treatment significantly changed the composition of the gut microbiota and destroyed the homeostasis in the intestinal metabolism. And the urinary AAA could be an indicator for exploring interactions between host and gut microbiota.     

Disparate Metabolic Responses in Mice Fed a High-Fat Diet Supplemented with Maize-Derived Non-Digestible Feruloylated Oligo- and Polysaccharides Are Linked to Changes in the Gut Microbiota

Studies have suggested links between colonic fermentation of dietary fibers and improved metabolic health. The objectives of this study were to determine if non-digestible feruloylated oligo- and polysaccharides (FOPS), a maize-derived dietary fiber, could counteract the deleterious effects of high-fat (HF) feeding in mice and explore if metabolic benefits were linked to the gut microbiota. C57BL/6J mice (n = 8/group) were fed a low-fat (LF; 10 kcal% fat), HF (62 kcal% fat), or HF diet supplemented with FOPS (5%, w/w). Pronounced differences in FOPS responsiveness were observed: four mice experienced cecal enlargement and enhanced short chain fatty acid production, indicating increased cecal fermentation (F-FOPS). Only these mice displayed improvements in glucose metabolism compared with HF-fed mice. Blooms in the gut microbial genera Blautia and Akkermansia were observed in three of the F-FOPS mice; these shifts were associated with reductions in body and adipose tissue weights compared with the HF-fed control mice. No improvements in metabolic markers or weights were detected in the four mice whose gut microbiota did not respond to FOPS. These findings demonstrate that FOPS-induced improvements in weight gain and metabolic health in mice depended on the ability of an individual’s microbiota to ferment FOPS.     

Effects of orally administered Bdellovibrio bacteriovorus on the well-being and Salmonella colonization of young chicks

Bdellovibrio bacteriovorus is a bacterium which preys upon and kills Gram-negative bacteria, including the zoonotic pathogens Escherichia coli and Salmonella. Bdellovibrio has potential as a biocontrol agent, but no reports of it being tested in living animals have been published, and no data on whether Bdellovibrio might spread between animals are available. In this study, we tried to fill this knowledge gap, using B. bacteriovorus HD100 doses in poultry with a normal gut microbiota or predosed with a colonizing Salmonella strain. In both cases, Bdellovibrio was dosed orally along with antacids. After dosing non-Salmonella-infected birds with Bdellovibrio, we measured the health and well-being of the birds and any changes in their gut pathology and culturable microbiota, finding that although a Bdellovibrio dose at 2 days of age altered the overall diversity of the natural gut microbiota in 28-day-old birds, there were no adverse effects on their growth and well-being. Drinking water and fecal matter from the pens in which the birds were housed as groups showed no contamination by Bdellovibrio after dosing. Predatory Bdellovibrio orally administered to birds that had been predosed with a gut-colonizing Salmonella enterica serovar Enteritidis phage type 4 strain (an important zoonotic pathogen) significantly reduced Salmonella numbers in bird gut cecal contents and reduced abnormal cecal morphology, indicating reduced cecal inflammation, compared to the ceca of the untreated controls or a nonpredatory ΔpilA strain, suggesting that these effects were due to predatory action. This work is a first step to applying Bdellovibrio therapeutically for other animal, and possibly human, infections.     

Targeting the gut microbiota with resveratrol: a demonstration of novel evidence for the management of hepatic steatosis

Resveratrol is a natural polyphenol that has been reported to reduce the risk of obesity and nonalcoholic fatty liver disease (NAFLD). Recent evidence has demonstrated that the gut microbiota plays an important role in the protection against NAFLD and other metabolic diseases. The present study aimed to investigate the relationship between the gut microbiota and the beneficial effects of resveratrol on the amelioration of NAFLD in mice. We observed marked decreases in body weight and liver steatosis and improved insulin resistance in high-fat diet (HFD)-fed mice treated with resveratrol. Furthermore, we found that resveratrol treatment alleviated NAFLD in HFD-fed mice by improving the intestinal microenvironment, including gut barrier function and gut microbiota composition. On the one hand, resveratrol improved gut intestinal barrier integrity through the repair of intestinal mucosal morphology and increased the expression of physical barrier- and physiochemical barrier-related factors in HFD-fed mice. On the other hand, in HFD-fed mice, resveratrol supplementation modulated the gut bacterial composition. The resveratrol-induced gut microbiota was characterized by a decreased abundance of harmful bacteria, including Desulfovibrio, Lachnospiraceae_NK4A316_group and Alistipes, as well as an increased abundance of short-chain fatty acid (SCFA)-producing bacteria, such as Allobaculum, Bacteroides and Blautia. Moreover, transplantation of the HFDR-microbiota into HFD-fed mice sufficiently decreased body weight, liver steatosis and low-grade inflammation and improved hepatic lipid metabolism. Collectively, resveratrol would provide a potentially dietary intervention strategy against NAFLD through modulating the intestinal microenvironment.     

Formation of propionate and butyrate by the human colonic microbiota

The human gut microbiota ferments dietary non‐digestible carbohydrates into short‐chain fatty acids (SCFA). These microbial products are utilized by the host and propionate and butyrate in particular exert a range of health‐promoting functions. Here an overview of the metabolic pathways utilized by gut microbes to produce these two SCFA from dietary carbohydrates and from amino acids resulting from protein breakdown is provided. This overview emphasizes the important role played by cross‐feeding of intermediary metabolites (in particular lactate, succinate and 1,2‐propanediol) between different gut bacteria. The ecophysiology, including growth requirements and responses to environmental factors, of major propionate and butyrate producing bacteria are discussed in relation to dietary modulation of these metabolites. A detailed understanding of SCFA metabolism by the gut microbiota is necessary to underpin effective strategies to optimize SCFA supply to the host.     

Combination of meal and exercise timing with a high-fat diet influences energy expenditure and obesity in mice

In mice, obesity has been observed not only in those freely fed a high-fat diet (HFD) but also in those fed while physically inactive. In contrast, a HFD during physically active periods protects against obesity and the impairments in the circadian rhythm induced by free feeding of a HFD. Although exercise is known to be effective for obesity prevention and management, the optimal timing of exercise has not yet been determined. In the present experiments, we aimed to determine the best combination of daily timing of HFD consumption and exercise for the prevention of HFD-induced weight gain in mice. In this experiment, “morning” refers to the beginning of the active phase (the “morning” for nocturnal animals). Increases in body weight related to free feeding of a HFD was significantly reduced with 4?h of exercise during the late (evening) or middle (noon) active period compared to 4?h of exercise during the early (morning) active period or free access to exercise, which resulted in hours of exercise similar to that of morning exercise. These results suggested that eating in the morning or at noon followed by exercise in the evening could prevent weight gain more effectively than exercise in the morning followed by eating at noon or in the evening. The group fed a HFD for 4?h in the morning had lower body weight than the group fed a HFD for 4?h in the evening without exercise. The last group of experiments tested the hypothesis that there would be an interaction between mealtime and exercise time (i.e. time of day) versus order (i.e. which comes first) effects. We compared groups that exercised for 4?h at noon and were fed either in the morning or evening and groups that were fed for 4?h at noon and either exercised in the morning or evening. We found that the groups that were fed before exercise gained less body and fat weight and more skeletal muscle weight compared to the groups that exercised before eating. Corresponding to the body and fat weight changes, the respiratory exchange ratio (RER) was lower and energy expenditure was higher in the groups fed before exercise than in the groups fed after exercise, and these effects on energy metabolism were also observed in the early stage of HFD feeding before obesity. When obese mice fed a HFD for 12 weeks were exposed to a combination of feeding and exercise timing in an effort to reduce body weight, eating followed by exercise resulted in greater weight loss, similar to the experiments conducted to prevent weight gain. These results demonstrate that a combination of daily timing of eating and exercise may influence weight gain and that eating followed by exercise may be effective for minimizing increases in body and fat weight as well as maximizing increases in skeletal muscle weight.     

Cranberries attenuate animal-based diet-induced changes in microbiota composition and functionality: a randomized crossover controlled feeding trial

Cranberries have multiple health effects but their impact on gut microbiota has not been examined in randomized controlled feeding trials. We evaluated the relationship between the microbiota and cranberries in the context of an animal-based diet. In a randomized, double-blind, cross-over, controlled design trial, 11 healthy adults consumed for 5 days each a control diet (animal-based diet plus 30 g/day placebo powder) and a cranberry diet (animal-based diet plus 30 g/day freeze-dried whole cranberry powder). The animal-based diet included meats, dairy products, and simple sugars. Stool, urine, and blood samples were obtained before and after each intervention phase. As compared to the pre-control diet, control diet modified 46 taxonomic clades, including an increase in the abundance of Firmicutes and decrease in Bacteroidetes. Moreover, it increased bacteria-derived deoxycholic acid and decreased acetate and butyrate in stool. As compared to the post-intervention phase of control diet, the cranberry diet modified 9 taxonomic clades, including a decrease in the abundance of Firmicutes and increase in Bacteroidetes. Further, the cranberry diet attenuated control diet-induced increase in secondary bile acids and decrease in short-chain fatty acids (SCFA), and increased urinary anthocyanins and bacterially derived phenolic acids. No changes were found in fecal trimethylamine and plasma cytokines. In conclusion, an animal-based diet altered the microbiota composition to a less favorable profile, increased carcinogenic bile acids, and decreased beneficial SCFA. Cranberries attenuated the impact of the animal-based diet on microbiota composition, bile acids, and SCFA, evidencing their capacity to modulate the gut microbiota.     

Fructose liquid and solid formulations differently affect gut integrity,microbiota composition and related liver toxicity: a comparative in vivo study

Despite clinical findings suggesting that the form (liquid versus solid) of the sugars may significantly affect the development of metabolic diseases, no experimental data are available on the impact of their formulations on gut microbiota, integrity and hepatic outcomes.In the present sudy, C57Bl/6j mice were fed a standard diet plus water (SD), a standard diet plus 60% fructose syrup (L-Fr) or a 60% fructose solid diet plus water (S-Fr) for 12 weeks. Gut microbiota was characterized through 16S rRNA phylogenetic profiling and shotgun sequencing of microbial genes in ileum content and related volatilome profiling.Fructose feeding led to alterations of the gut microbiota depending on the fructose formulation, with increased colonization by Clostridium, Oscillospira and Clostridiales phyla in the S-Fr group and Bacteroides, Lactobacillus, Lachnospiraceae and Dorea in the L-Fr. S-Fr evoked the highest accumulation of advanced glycation end products and barrier injury in the ileum intestinal mucosa. These effects were associated to a stronger activation of the lipopolysaccharide-dependent proinflammatory TLR4/NLRP3 inflammasome pathway in the liver of S-Fr mice than of L-Fr mice. In contrast, L-Fr intake induced higher levels of hepatosteatosis and markers of fibrosis than S-Fr. Fructose-induced ex novo lipogenesis with production of SCFA and MCFA was confirmed by metagenomic analysis.These results suggest that consumption of fructose under different forms, liquid or solid, may differently affect gut microbiota, thus leading to impairment in intestinal mucosa integrity and liver homeostasis.     

Pediococcus pentosaceus LI05 alleviates DSS-induced colitis by modulating immunological profiles,the gut microbiota and short-chain fatty acid levels in a mouse model

The gut microbiota is considered a key factor in pathogenesis and progression of inflammatory bowel disease (IBD). The bacterium Pediococcus pentosaceus LI05 alleviated host inflammation by maintaining the gut epithelial integrity, modulating the host immunity, gut microbiota and metabolism, but its effect on IBD remains unclear. The present study aimed to investigate the role and mechanisms of P. pentosaceus LI05. Mice were administered P. pentosaceus LI05 or phosphate-buffered saline once daily by oral gavage for 14 days, and colitis was induced by providing mice 2% DSS-containing drinking water for 7 days. P. pentosaceus LI05 ameliorated colitis in mice and reduced the body weight loss, disease activity index (DAI) scores, colon length shortening, intestinal permeability and the proinflammatory cytokine levels. Furthermore, a significantly altered gut microbiota composition with increased diversity and short-chain fatty acid (SCFA) production was observed in mice treated with P. pentosaceus LI05. Several genera, including Akkermansia and Faecalibacterium, were differentially enriched in the P. pentosaceus LI05-treated mice and were negatively correlated with colitis indices and positively correlated with gut barrier markers and SCFA levels. The P. pentosaceus LI05 treatment alleviated intestinal inflammation by maintaining the intestinal epithelial integrity and modulating the immunological profiles, gut microbiome and metabolite composition. Based on our findings, P. pentosaceus LI05 might be applied as potential preparation to ameliorate colitis.     

The Role of Intestinal Microbiota in Development of Irinotecan Toxicity and in Toxicity Reduction through Dietary Fibres in Rats

CPT-11 is a drug used as chemotherapy for colorectal cancer. CPT-11 causes toxic side-effects in patients. CPT-11 toxicity has been attributed to the activity of intestinal microbiota, however, intestinal microbiota may also have protective effects in CP!-11 chemotherapy. This study aimed to elucidate mechanisms through which microbiota and dietary fibres could modify host health. Rats bearing a Ward colon carcinoma were treated with a two-cycle CPT-11/5-fluorouracil therapy recapitulating clinical therapy of colorectal cancer. Animals were fed with a semi-purified diet or a semi-purified diet was supplemented with non-digestible carbohydrates (isomalto-oligosaccharides, resistant starch, fructo-oligosaccharides, or inulin) in 3 independent experiments. Changes in intestinal microbiota, bacteria translocating to mesenteric lymphnodes, cecal GUD activity, and cecal SCFA production, and the intestinal concentration of CPT-11 and its metabolites were analysed. Non-digestible carbohydrates significantly influenced feed intake, body weight and other indicators of animal health. The identification of translocating bacteria and their quantification in cecal microbiota indicated that overgrowth of the intestine by opportunistic pathogens was not a major contributor to CPT-11 toxicity. Remarkably, fecal GUD activity positively correlated to body weight and feed intake but negatively correlated to cecal SN-38 concentrations and IL1-β. The reduction in CPT-11 toxicity by non-digestible carbohydrates did not correlate to stimulation of specific bacterial taxa. However, cecal butyrate concentrations and feed intake were highly correlated. The protective role of intestinal butyrate production was substantiated by a positive correlation of the host expression of MCT1 (monocarboxylate transporter 1) with body weight as well as a positive correlation of the abundance of bacterial butyryl-CoA gene with cecal butyrate concentrations. These correlations support the interpretation that the influence of dietary fibre on CPT-11 toxicity is partially mediated by an increased cecal production of butyrate.     

Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling

Rationale: Dysbiotic gut microbiota (GM) and NLRP3 inflammasome are proarrhythmic factors in atrial fibrillation (AF). Herein, whether short-chain fatty acid (SCFA) produced from GM fermentation of dietary fiber serving as invisible mediators is yet unclear. Thus, the current study aimed to determine whether SCFA alleviated from NLRP3 signaling-mediated atrial remodeling protects AF development.Methods: First, a cross-sectional study based on the GC-MS metabolomics was performed to explore the association between fecal SCFA levels and AF traits in a cohort consisted of 48 individuals. Then, a well-established mice model fed diet deficient or enriched in dietary fiber was established to elucidate the pathophysiological role of SCFA involved in AF susceptibility, atrial remodeling, and G-protein-coupled receptor 43 (GPR43)/NLRP3 signaling. Finally, the effects of SCFA were verified on HL-1 cells.Results: Fecal SCFA levels were remarkably reduced in AF patients with a declining trend from paroxysmal to persistent AF. Prolonged P wave duration based on surface ECG and increased left atrial diameter gained from echocardiography was identified in low-fiber diet mice but lost in SCFA-supplemented group. Lack of dietary fiber enhanced susceptibility to AF under burst pacing, whereas SCFA might exert a protective effect. The supplementation of SCFA prevented dietary fiber deficiency-upregulated phosphorylation of calmodulin-dependent protein kinase II and ryanodine receptor 2, the disarray fibrosis, collagen expression, and NLRP3 inflammasome activation in atrial tissue. Finally, the AF protective roles of SCFA were identified through GPR43 mediated deactivation of NLRP3 by GPR43 knockdown in HL-1 cells.Conclusions: SCFA derived from dietary fiber fermentation by gut commensals alleviates AF development via GPR43/NLRP3 signaling.     

The Physico-Chemical Properties of Dietary Fibre Determine Metabolic Responses,Short-Chain Fatty Acid Profiles and Gut Microbiota Composition in Rats Fed Low- and High-Fat Diets

The aim of this study was to investigate how physico-chemical properties of two dietary fibres, guar gum and pectin, affected weight gain, adiposity, lipid metabolism, short-chain fatty acid (SCFA) profiles and the gut microbiota in male Wistar rats fed either low- or high-fat diets for three weeks. Both pectin and guar gum reduced weight gain, adiposity, liver fat and blood glucose levels in rats fed a high-fat diet. Methoxylation degree of pectin (low, LM and high (HM)) and viscosity of guar gum (low, medium or high) resulted in different effects in the rats, where total blood and caecal amounts of SCFA were increased with guar gum (all viscosities) and with high methoxylated (HM) pectin. However, only guar gum with medium and high viscosity increased the levels of butyric acid in caecum and blood. Both pectin and guar gum reduced cholesterol, liver steatosis and blood glucose levels, but to varying extent depending on the degree of methoxylation and viscosity of the fibres. The medium viscosity guar gum was the most effective preparation for prevention of diet-induced hyperlipidaemia and liver steatosis. Caecal abundance of Akkermansia was increased with high-fat feeding and with HM pectin and guar gum of all viscosities tested. Moreover, guar gum had distinct bifidogenic effects independent of viscosity, increasing the caecal abundance of Bifidobacterium ten-fold. In conclusion, by tailoring the viscosity and possibly also the degree of methoxylation of dietary fibre, metabolic effects may be optimized, through a targeted modulation of the gut microbiota and its metabolites.     

Astragaloside IV alleviates mouse slow transit constipation by modulating gut microbiota profile and promoting butyric acid generation

Gut microbiota and short‐chain fatty acids (SCFAs) are associated with the development of various human diseases. In this study, we examined the role of astragaloside IV in modulating mouse gut microbiota structure and the generation of SCFAs, as well as in slow transit constipation (STC). An STC model was established by treating mice with loperamide, in which the therapeutic effects of astragaloside IV were evaluated. The microbiota community structure and SCFA content were analysed by 16S rRNA gene sequencing and gas chromatography‐mass spectrometry, respectively. The influence of butyrate on STC was assessed using a mouse model and Cajal cells (ICC). Astragaloside IV promoted defecation, improved intestinal mobility, suppressed ICC loss and alleviated colonic lesions in STC mice. Alterations in gut microbiota community structure in STC mice, such as decreased Lactobacillus reuteri diversity, were improved following astragaloside IV treatment. Moreover, astragaloside IV up‐regulated butyric acid and valeric acid, but decreased isovaleric acid, in STC mouse stools. Butyrate promoted defecation, improved intestinal mobility, and enhanced ICC proliferation by regulating the AKT–NF‐κB signalling pathway. Astragaloside IV promoted intestinal transit in STC mice and inhibited ICC loss by regulating the gut microbiota community structure and generating butyric acid.     

运动、肠道菌群代谢物——短链脂肪酸与骨骼肌代谢调控

寄生于人体的肠道菌群是一个高度动态化和个体化的复杂生态系统,受遗传、环境、饮食、年龄和运动等因素的影响,并通过其产生的代谢物与机体众多组织器官产生广泛的应答效应。短链脂肪酸(short chain fatty acid, SCFA)主要是由位于盲肠和结肠内的菌群以膳食纤维为底物发酵产生,其被吸收进入肠系膜上下静脉,随后汇入门静脉至肝。部分短链脂肪酸被肝作为糖异生和脂质合成的底物,剩余的短链脂肪酸以游离脂肪酸的形式经肝静脉进入外周循环。研究发现,运动可使产生SCFA的肠道菌群组分的丰度提高和参与调控SCFA生成的相关基因表达增加,使肠道中短链脂肪酸含量增加。由短链脂肪酸刺激结肠内分泌细胞合成分泌的胰高血糖素样肽1(glucagon like peptide-1, GLP-1)可促使胰岛B细胞合成分泌胰岛素,进而调节骨骼肌的葡萄糖摄取与糖原合成。此外,短链脂肪酸通过提高骨骼肌胰岛素受体底物1(insulin receptor substrate 1,IRS1)基因转录起始位点附近的组蛋白乙酰化水平,增强骨骼肌的胰岛素敏感性。同时,短链脂肪酸通过激活腺苷酸活化蛋白质激酶(AMP-activated protein kinase, AMPK)促进骨骼肌的脂肪酸摄取、脂肪分解和线粒体生物发生,抑制脂肪合成。本文就肠道菌群代谢物——短链脂肪酸概述、运动对产生短链脂肪酸的肠道菌群的影响和运动介导肠道菌群代谢物——短链脂肪酸对骨骼肌代谢调控机制的最新研究进展进行综述,为骨骼肌运动适应的新机制研究提供理论依据。     

肠道微生态与肥胖

人的肠道是一个丰富的微生态系统,含有100万亿多的微生物,种类多达500-1000个,这些微生物的基因总数是人体基因组所含基因总数的100倍。肠道微生物丛的组成种类和数量与宿主的肥胖有关,无菌小鼠含有的脂肪量比正常饲养小鼠低42％,如果将微生物丛植入到无菌小鼠体内后,导致脂肪总量增加57％。提示肠道微生物丛可以明显的促进小鼠对热能的摄人,促使脂肪的沉积,触动全身性炎症反应。因此,对肥胖的治疗可以采用益生菌和益生元来调节肠道微生物丛的状态以期获得治疗效果。本研究述及肠道微生丛对宿主肥胖及其代谢机制的研究进展。     

Dietary Resistant Starch Alters the Characteristics of Colonic Mucosa and Exerts a Protective Effect on Trinitrobenzene Sulfonic Acid-induced Colitis in Rats

The protective effect of a dietary high-amylose cornstarch (HAS) against trinitrobenzene sulfonic acid (TNBS)-induced colitis was examined in rats. Rats were fed a HAS-free basal diet or, a 15% or 30% HAS supplemented diet for 10 d, and then received intracolonic TNBS to induce colitis and fed the respective diets for a further 8 d. HAS ingestion significantly protected colonic injuries as evidenced by lower colonic myeloperoxidase activity. Rats fed the HAS diet showed greater cecal short-chain fatty acid (SCFA) production than those fed the basal diet. Further, just before TNBS administration, HAS ingestion dose-dependently increased fecal and cecal mucin contents, and protein and nucleic acid contents in the colonic mucosa. HAS ingestion also reduced colonic permeability. The protective effect of HAS ingestion on TNBS-induced colitis is perhaps exerted through alterations in colonic mucosa, possibly due to cecal SCFA production.     

Dietary resistant starch alters the characteristics of colonic mucosa and exerts a protective effect on trinitrobenzene sulfonic acid-induced colitis in rats

The protective effect of a dietary high-amylose cornstarch (HAS) against trinitrobenzene sulfonic acid (TNBS)-induced colitis was examined in rats. Rats were fed a HAS-free basal diet or, a 15% or 30% HAS supplemented diet for 10 d, and then received intracolonic TNBS to induce colitis and fed the respective diets for a further 8 d. HAS ingestion significantly protected colonic injuries as evidenced by lower colonic myeloperoxidase activity. Rats fed the HAS diet showed greater cecal short-chain fatty acid (SCFA) production than those fed the basal diet. Further, just before TNBS administration, HAS ingestion dose-dependently increased fecal and cecal mucin contents, and protein and nucleic acid contents in the colonic mucosa. HAS ingestion also reduced colonic permeability. The protective effect of HAS ingestion on TNBS-induced colitis is perhaps exerted through alterations in colonic mucosa, possibly due to cecal SCFA production.     

Timing of food intake is more potent than habitual voluntary exercise to prevent diet-induced obesity in mice

Inappropriate eating habits such as skipping breakfast and eating late at night are associated with risk for abnormal weight-gain and adiposity. We previously reported that time-imposed feeding during the daytime (inactive phase) induces obesity and metabolic disorders accompanied by physical inactivity in mice. The present study compares metabolic changes induced in mice by time-imposed feeding under voluntary wheel-running (RW) and sedentary (SED) conditions to determine the effects of voluntary wheel-running activity on obesity induced in mice by feeding at inappropriate times. Mice were individually housed in cages with or without running-wheels. We compared food consumption, core body temperature, hormonal and metabolic variables in the blood, lipid accumulation in the liver, circadian expression of clock and metabolic genes in peripheral tissues, and gains in body weight between mice allowed access to food only during the sleep phase (daytime feeding; DF) or only during the active phase (nighttime feeding; NF) under SED or RW conditions. Only a high-fat high-sucrose diet was available to the mice throughout restricted feeding. Nocturnal activity was maintained in both NF and DF mice under RW conditions, but significantly suppressed during the latter half of the dark phase in DF mice. Nocturnal fluctuations in core body temperature were maintained in DF and NF mice under both SED and RW conditions, although DF attenuated the day–night amplitude more under SED, than RW conditions. The degrees of DF-induced increases in body weight gain, food efficiency, adipose tissue mass, lipogenic gene expression in metabolic tissues, and hepatic lipid accumulation were essentially identical between SED and RW conditions. Daytime feeding also induced hyperinsulinemia and hyperleptinemia under both SED and RW conditions, although DF-induced hyperleptinemia was slightly attenuated by wheel-running. The temporal expression of circadian clock genes became synchronized to feeding cycles in the liver but not in the skeletal muscle of mice under both SED and RW conditions. Chronic voluntary exercise on running-wheels minimally affected obesity and adiposity in mice caused by daily feeding at unusual times. The timing of food intake might be more important than physical exercise for preventing metabolic disorders.

Abbreviations: ANOVA: analysis of variance; DF: daytime feeding; FFA: free fatty acid; GLP-1: glucagon-like peptide-1; HOMA-IR: homeostasis model assessment of insulin resistance; NEAT: non-exercise activity thermogenesis; NF: nighttime feeding; RF: restricted feeding; RW: running-wheel; SCN: suprachiasmatic nucleus; SE: standard error of the mean; SED: sedentary; SPA: spontaneous physical activity; T-Cho: total cholesterol; TG: triglyceride; WAT: white adipose tissues