High‐fat diet‐induced dysbiosis mediates MCP‐1/CCR2 axis‐dependent M2 macrophage polarization and promotes intestinal adenoma‐adenocarcinoma sequence

High‐fat diet (HFD) is a well‐known risk factor for gut microbiota dysbiosis and colorectal cancer (CRC). However, evidence relating HFD, gut microbiota and carcinogenesis is limited. Our study aimed to demonstrate that HFD‐induced gut dysbiosis promoted intestinal adenoma‐adenocarcinoma sequence. In clinical study, we found that HFD increased the incidence of advanced colorectal neoplasia (AN). The expression of monocyte chemoattractant protein 1 (MCP‐1), CC chemokine receptor 2 (CCR2) and CD163 in CRC patients with HFD was significantly higher than that in CRC patients with normal diet. When it comes to the Apc^min/+ mice, HFD consumption could induce gut dysbiosis and promote intestinal carcinogenesis, accompanying with activation of MCP‐1/CCR2 axis that recruited and polarized M2 tumour‐associated macrophages. Interestingly, transfer of faecal microbiota from HFD‐fed mice to another batch of Apc^min/+ mice in the absence of HFD could also enhance carcinogenesis without significant body weight gain and induced MCP‐1/CCR2 axis activation. HFD‐induced dysbiosis could also be transmitted. Meanwhile, antibiotics cocktail treatment was sufficient to inhibit HFD‐induced carcinogenesis, indicating the vital role of dysbiosis in cancer development. Conclusively, these data indicated that HFD‐induced dysbiosis accelerated intestinal adenoma‐adenocarcinoma sequence through activation of MCP‐1/CCR2 axis, which would provide new insight into better understanding of the mechanisms and prevention for HFD‐related CRC.     

Spirulina platensis alleviates chronic inflammation with modulation of gut microbiota and intestinal permeability in rats fed a high‐fat diet

Recent research suggested that taking a high‐fat diet (HFD) may lead to a gut microbiota imbalance and colon tissue damage. This would lead to increased intestinal permeability and consequent constant circulation of low‐grade inflammatory cytokines. Spirulina platensis can protect against HFD‐induced metabolic inflammation and can stimulate the growth of beneficial bacteria in in vitro stool cultures. However, it is unknown whether this beneficial effect acts on intestinal tissues. In this study, rats were fed a high‐fat diet fed with 3% S platensis for 14 weeks. We analysed endotoxin, the composition of the microbiota, inflammation and gut permeability. We found that S platensis decreased the bodyweight and visceral fat pads weight of the HFD‐fed rats. In addition, it lowered the levels of lipopolysaccharide and pro‐inflammatory cytokines in serum. Our results showed that S platensis could largely reduce the relative amount of Proteobacteria and the Firmicutes/Bacteroidetes ratio in faecal samples from HFD‐fed rats. S platensis significantly reduced intestinal inflammation, as shown by decreased expression of myeloid differentiation factor 88 (MyD88), toll‐like receptor 4 (TLR4), NF‐κB (p65) and inflammatory cytokines. S platensis also ameliorated the increased permeability and decreased expression of tight junction proteins in the intestinal mucosa, such as ZO‐1, Occludin and Claudin‐1. Therefore, in HFD‐induced gut dysbiosis rats, S platensis benefits health by inhibiting chronic inflammation and gut dysbiosis, and modulating gut permeability.     

Amelioration of non-alcoholic steatohepatitis by Qushi Huayu decoction is associated with inhibition of the intestinal mitogen-activated protein kinase pathway

BackgroundGut microbiota is increasingly recognized as the key participant in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) by translocation of its products, such as lipopolysaccharide (LPS), via the dysfunctional intestinal barrier. Qushi Huayu decoction (QHD), a traditional Chinese medicine, is developed specially for NAFLD and used in clinic in China for more than a decade and previously found to ameliorate non-alcoholic steatohepatitis (NASH) induced by high-fat diet (HFD) in mice accompanied with inhibited metabolic endotoxemia and hepatic LPS signalling.PurposeTo investigate the mechanism of LPS gut-leakage inhibition by QHD in NASH.MethodsEffects of QHD on gut microbioa and intestinal barrier were evaluated in NASH induced by HFD in mice. 16S rRNA sequencing is employed to analyse the gut microbiota composition. To identify the potential signalling pathway responsible for tight junction regulation, the colonic phosphoprotein profile is screened via the Phospho Explorer Antibody Array and verified in NASH, intestinal barrier dysfunctional mouse and Caco-2 cells.ResultsQHD ameliorates NASH accompanied with regulating the gut microbiota composition, protecting intestinal tight junctions and inhibiting LPS gut-leakage without decreasing the abundance of identified Gram-negative bacteria. The validated data of phosphorylated proteins suggested that mitogen-activated protein kinase (MAPK) pathway is predominantly responsible for the colonic tight junction regulation by QHD.ConclusionQHD inhibits LPS gut-leakage in NASH, which is associated with downregulation of intestinal MAPK pathway.     

Alterations in gut microbiota and metabolites associated with altitude-induced cardiac hypertrophy in rats during hypobaric hypoxia challenge

The gut microbiota is involved in host responses to high altitude. However, the dynamics of intestinal microecology and their association with altitude-related illness are poorly understood. Here, we used a rat model of hypobaric hypoxia challenge to mimic plateau exposure and monitored the gut microbiome, short-chain fatty acids (SCFAs), and bile acids (BAs) over 28 d. We identified weight loss, polycythemia, and pathological cardiac hypertrophy in hypoxic rats, accompanied by a large compositional shift in the gut microbiota, which is mainly driven by the bacterial families of Prevotellaceae, Porphyromonadaceae, and Streptococcaceae. The aberrant gut microbiota was characterized by increased abundance of the Parabacteroides, Alistipes, and Lactococcus genera and a larger Bacteroides to Prevotella ratio. Trans-omics analyses showed that the gut microbiome was significantly correlated with the metabolic abnormalities of SCFAs and BAs in feces, suggesting an interaction network remodeling of the microbiome-metabolome after the hypobaric hypoxia challenge. Interestingly, the transplantation of fecal microbiota significantly increased the diversity of the gut microbiota, partially inhibited the increased abundance of the Bacteroides and Alistipes genera, restored the decrease of plasma propionate, and moderately ameliorated cardiac hypertrophy in hypoxic rats. Our results provide an insight into the longitudinal changes in intestinal microecology during the hypobaric hypoxia challenge. Abnormalities in the gut microbiota and microbial metabolites contribute to the development of high-altitude heart disease in rats.

     

Cidec基因敲除小鼠肠道菌群的特征

目的:探究Cidec敲除(CIDEC-KO)小鼠肠道菌群的结构。方法:随机分别挑选体重相近、2月龄5只野生型和5只Cidec敲除的雄性小鼠,收集两种基因型小鼠经高脂饲料16周喂养前后的新鲜粪便。提取粪便中的细菌基因组,对菌群基因组16S r RNA基因V4高变区进行测序,对数据进行PCoA分析、Alpha多样性分析及LEf Se分析。结果:属水平下的LEf Se分析显示,在普通饲料喂养条件下,Cidec缺失小鼠对比野生型小鼠粪便中PrevotellaceaUCG001属丰度显著上升,Blautia属、Streptococcus属、LachnospiraceaeUCG006属丰度显著下降。与同月龄同高脂喂养的野生型小鼠比,Cidec敲除小鼠粪便中RuminococcaceaeUCG014属丰度显著下降。进一步比较同一种基因型下饮食对肠道菌群的改变,发现在喂养高脂饲料后,某些属的丰度仅在Cidec缺失小鼠中发生显著变化,但是在野生型小鼠中未发现有显著变化,这些属包括:Alistipes属、Bacteroides属、Paraprevotella属、Streptococcus属、LachnospiraceaeUCG006属丰度显著上升。而喂养高脂后,仅在野生型小鼠中发现Peptococcus属和Ruminococcustorquesgroup属丰度的显著上升,以及Tyzzerella3属、Ruminiclostidium6属和A2属丰度的显著下降,在Cidec缺失小鼠粪便中并未发现这些属的丰度有显著变化。结论:高脂诱导下,对比野生型小鼠,某些同代谢综合征正相关的属只在Cidec缺失小鼠肠道菌群中丰度显著上升。     

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.     

Bile acid is a significant host factor shaping the gut microbiome of diet-induced obese mice

Background

Intestinal bacteria are known to regulate bile acid (BA) homeostasis via intestinal biotransformation of BAs and stimulation of the expression of fibroblast growth factor 19 through intestinal nuclear farnesoid X receptor (FXR). On the other hand, BAs directly regulate the gut microbiota with their strong antimicrobial activities. It remains unclear, however, how mammalian BAs cross-talk with gut microbiome and shape microbial composition in a dynamic and interactive way.

Results

We quantitatively profiled small molecule metabolites derived from host-microbial co-metabolism in mice, demonstrating that BAs were the most significant factor correlated with microbial alterations among all types of endogenous metabolites. A high-fat diet (HFD) intervention resulted in a rapid and significant increase in the intestinal BA pool within 12 h, followed by an alteration in microbial composition at 24 h, providing supporting evidence that BAs are major dietary factors regulating gut microbiota. Feeding mice with BAs along with a normal diet induced an obese phenotype and obesity-associated gut microbial composition, similar to HFD-fed mice. Inhibition of hepatic BA biosynthesis under HFD conditions attenuated the HFD-induced gut microbiome alterations. Both inhibition of BAs and direct suppression of microbiota improved obese phenotypes.

Conclusions

Our study highlights a liver–BA–gut microbiome metabolic axis that drives significant modifications of BA and microbiota compositions capable of triggering metabolic disorders, suggesting new therapeutic strategies targeting BA metabolism for metabolic diseases.

     

Influence of high-fat diet on host animal health via bile acid metabolism and benefits of oral-fed Streptococcus thermophilus MN-ZLW-002

In this study, C57BL/6J male mice were fed normal chow (NC; control) or a high-fat diet (HFD) for 12 weeks, and HFD mice were supplemented with oral administration of Streptococcus thermophilus MN-ZLW-002 (HFD + MN002); n=20/group. Body weight, visceral fat, blood glucose, blood lipids and liver lipid deposition increased in the HFD group, and the composition of gut microbiota, cecum short-chain fatty acids and fecal bile acids (BAs) also changed. Oral-fed MN-002 increased the relative abundances of Ruminococcaceae, Lachnospiraceae and Streptococcaceae and improved blood glucose, liver cholesterol deposition, and serum IL-10, CCL-3 and the fecal BAs composition. In conclusion, the high-fat diet changed the composition of bile acids by shaping the gut microbiota into an obese type, leading to metabolic disturbances. Streptococcus thermophilus MN-ZLW-002 regulated gut microbiota by adjusting the composition of bile acids and improved the perturbation caused by high-fat diets. However, the effect of MN002 observed in animal experiments needs to be verified by long-term clinical trials.     

鄱阳湖越冬白鹤肠道微生物群落结构及功能预测分析

【目的】分析鄱阳湖越冬白鹤在人工生境中肠道微生物群落组成和代谢功能特征。【方法】利用16S rRNA基因高通量测序技术比较藕田和稻田2种不同人工生境鄱阳湖越冬白鹤肠道微生物群落组成和重建未观察到的状态(phylogenetic investigation of communities by reconstruction of unobserved states, PICRUSt)进行功能预测。【结果】稻田白鹤肠道微生物α多样性(Ace、Chao1、Shannon和Simpson指数)高于藕田白鹤,但未达到显著水平(P>0.05)。基于Binary-Jaccard距离矩阵的β多样性分析发现2种人工生境的白鹤肠道微生物群落结构差异显著(R²=0.312, P<0.05)。不同人工生境鄱阳湖越冬白鹤肠道微生物组成存在差异,藕田白鹤肠道微生物的优势菌属是土孢杆菌属、罗布西亚属和苏黎世杆菌属;稻田白鹤肠道微生物的优势菌属是乳酸杆菌属、里氏杆菌属和球菌属。线性判别分析[line discriminant analysis (LDA) effect size, LEfSe]分析发现乳杆菌科、乳酸杆菌属、苏黎世杆菌属等具有较强发酵代谢碳水化合物能力的微生物在2种人工生境下差异显著。PICRUSt功能预测表明鄱阳湖越冬白鹤肠道微生物与新陈代谢、基因信息处理、环境信息处理和人类疾病等功能相关,在level 1水平上,有5类代谢通路具有显著性差异(P<0.001)。【结论】两种人工生境中鄱阳湖越冬白鹤肠道微生物组成和群落特征差异较大,可能是由于同域觅食鸟类的种类、数量以及食物来源的不同。同时,PICRUSt功能预测揭示了不同人工生境中鄱阳湖越冬白鹤肠道微生物功能基因丰度的显著差异,表明白鹤可以通过调整自身肠道微生物组成来适应不同人工生境食物资源的变化带来的挑战。本研究对不同人工生境下白鹤肠道微生物的组成和功能潜力的研究结果可以为鄱阳湖越冬白鹤肠道微生物的研究提供一定依据,对于白鹤的保护和制定管理策略具有一定的参考价值和现实意义。     

Dysbiosis of intestinal homeostasis contribute to Whitmania pigra edema disease

Whitmania pigra is widely used in traditional Chinese medicine. However, W. pigra is being threatened by an edema disease with unknown causes (WPE). In this study, a comprehensive exploration of virome, microbiome, and metabolome aberrations in the intestine of W. pigra was performed to address the aetiology of WPE. Virome analysis indicated that eukaryotic viruses did not contribute to WPE, whereas an expansion of Caudovirales was observed in WPE. Compared to the control, the microbial richness and diversity in diseased W. pigra decreased remarkably. Nine genera, including Aeromonas, Anaerotruncus, Vibrio, Proteocatella, Acinetobacter, and Brachyspira were overrepresented in WPE, whereas eleven genera, including Bifidobacterium, Phascolarctobacterium, Lactobacillus, Bacillus and AF12, were enriched in healthy individuals. Furthermore, certain metabolites, especially amino acids, short-chain fatty acids, and bile acids, were found to be linked to intestinal microbiota alterations in WPE. An integration of the microbiome and metabolome in WPE found that dysbiosis of the gut microbiota or metabolites caused WPE. Notably, W. pigra accepted intestinal microbiota transplantation from WPE donors developed WPE clinical signs eventually, and the dysbiotic intestinal microbiota can be recharacterized in this recipient W. pigra. Strikingly, pathological features of metanephridium and uraemic toxin enrichment in the gut indicated a putative interconnection between the gut and metanephridium in WPE, which represents the prototype of the gut–kidney axis in mammals. These finding exemplify the conservation of “microecological Koch's postulates” from annelids to insects and other vertebrates, which provides a direction of prevention and treatment for WPE and opens a new insight into the pathogenesis of aquatic animal diseases from an ecological perspective.     

Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice

Obesity and type 2 diabetes are characterized by subclinical inflammatory process. Changes in composition or modulation of the gut microbiota may play an important role in the obesity-associated inflammatory process. In the current study, we evaluated the effects of probiotics (Lactobacillus rhamnosus, L. acidophilus and Bifidobacterium bifidumi) on gut microbiota, changes in permeability, and insulin sensitivity and signaling in high-fat diet and control animals. More importantly, we investigated the effects of these gut modulations on hypothalamic control of food intake, and insulin and leptin signaling. Swiss mice were submitted to a high-fat diet (HFD) with probiotics or pair-feeding for 5 weeks. Metagenome analyses were performed on DNA samples from mouse feces. Blood was drawn to determine levels of glucose, insulin, LPS, cytokines and GLP-1. Liver, muscle, ileum and hypothalamus tissue proteins were analyzed by Western blotting and real-time polymerase chain reaction. In addition, liver and adipose tissues were analyzed using histology and immunohistochemistry. The HFD induced huge alterations in gut microbiota accompanied by increased intestinal permeability, LPS translocation and systemic low-grade inflammation, resulting in decreased glucose tolerance and hyperphagic behavior. All these obesity-related features were reversed by changes in the gut microbiota profile induced by probiotics. Probiotics also induced an improvement in hypothalamic insulin and leptin resistance. Our data demonstrate that the intestinal microbiome is a key modulator of inflammatory and metabolic pathways in both peripheral and central tissues. These findings shed light on probiotics as an important tool to prevent and treat patients with obesity and insulin resistance.     

Bifidobacterium CECT 7765 improves metabolic and immunological alterations associated with obesity in high‐fat diet‐fed mice

Objectives: To evaluate the effects of administration of Bifidobacterium pseudocatenulatum CECT 7765 on metabolic and immune alterations in obese mice. Design and Methods: Adult male wild‐type C57BL‐6 mice were fed a standard diet or high‐fat diet (HFD), supplemented or not with B. pseudocatenulatum CECT 7765 for 7 weeks. The assessments included biochemical and immunological parameters, insulin resistance, glucose tolerance, histology of liver, white‐adipose and intestinal tissues, immunocompetent cell functions, and microbiota‐related features. Results: B. pseudocatenulatum CECT 7765 reduced serum cholesterol, triglyceride, and glucose levels and decreased insulin resistance and improved glucose tolerance in obese mice. This strain reduced serum levels of leptin, interleukin (IL)‐6 and monocyte chemotactic protein‐1, while increased those of IL‐4 in HFD‐fed mice. B. pseudocatenulatum CECT7765 reduced liver steatosis and the number of larger adipocytes and number of fat micelles in enterocytes of obese mice. The strain also improved the function of macrophages and dendritic cells in relation to phagocytosis, cytokine production, and induction of T‐lymphocyte proliferation. The strain administration increased bifidobacteria and reduced enterobacteria and the inflammatory properties of the gut content in HFD‐fed mice. Conclusion: B. pseudocatenulatum CECT 7765 was shown to ameliorate both metabolic and immunological dysfunctions related to obesity in HFD‐fed mice.     

Changes in intestinal microbiota across an altitudinal gradient in the lizard Phrynocephalus vlangalii

High altitude is an important driving force in animal evolution. However, the effect of altitude on gut microbial communities in reptiles has not been examined in detail. Here, we investigated the intestinal microbiota of three populations of the lizard Phrynocephalus vlangalii living at different altitudes using 16S rRNA gene sequencing. Bacteroidetes, Firmicutes, and Proteobacteria were the most abundant phyla. Bacteroides, Odoribacter, and Parabacteroides were the most abundant genera. Significant differences in the intestinal microbiota composition were found among the three populations from different altitudes. The proportions of Verrucomicrobia and Akkermansia decreased, whereas Bacteroides increased significantly with altitude. Greater abundance of Bacteroides at higher altitude led to the fractional increase in the phylum Bacteroides relative to other phyla. Hypoxia may be the main factor that caused intestinal microbiota variation in P. vlangalii along the altitude gradient. Overall, our study suggested that the community composition and structure of intestinal microbiota of the lizard P. vlangalii varied along altitudes, and such differences likely play a certain role in highland adaptation. Our findings warrant a further study that would determine whether ambient and body temperatures play a key role in the modulation of intestinal microbiota in reptiles.     

Liraglutide modulates gut microbiota and reduces NAFLD in obese mice

Metabolic disorders such as insulin resistance and diabetes are associated with obesity and nonalcoholic fatty liver disease (NAFLD). The aggressive form of a fatty liver disease may progress to cirrhosis and hepatocellular carcinoma. Furthermore, recent studies demonstrated that there is a dysbiosis in the gut microbiota associated with early stages of metabolic disease. Therefore, the identification and repurposing of drugs already used to treat insulin resistance may be an excellent option for other disorders. We evaluated the effect of liraglutide on obesity, NAFLD and gut microbiota modulation in two different animal models of obesity: the ob/ob mice and the high-fat diet (HFD)-fed mice. Liraglutide treatment induced significant weight loss in both obesity models, showed improvements in glycemic parameters and reduced inflammatory cell infiltration in the cecum and the liver. In ob/ob mice, the liraglutide treatment was able to reduce the accumulation of liver fat by 78% and reversed steatosis in the HFD mice. The gut microbiota analysis showed that liraglutide changed the overall composition as well as the relative abundance of weight-relevant phylotypes such as a reduction of Proteobacteria and an increase of Akkermansia muciniphila in the treated HFD group. We show that liraglutide can lead to weight loss and gut microbiota modulations, and is associated with an improvement of NAFLD. Furthermore, by generating a profile of the intestinal microbiota, we compiled a list of potential bacterial targets that may modulate metabolism and induce a metabolic profile that is considered normal or clinically controlled.     

Empagliflozin ameliorates type 2 diabetes mellitus-related diabetic nephropathy via altering the gut microbiota

BackgroundThe dysregulation of gut microbiota can be found in patients with type 2 diabetes mellitus (T2DM)-related diabetic nephropathy (DN). Inhibitors of sodium-glucose co-transporter 2 (SGLT2) were reported to affect gut microbiota. This study aimed to identify whether empagliflozin (EMPA) attenuated DN via regulating gut microbiota.Materials and methodsThe high-fat diet (HFD) combining streptozocin (STZ) injection was performed to induce DN in mice. The therapeutic effects of EMPA were observed by staining of renal tissues and urine albumin/creatinine ratio (UACR). Mouse feces were collected for 16S rRNA sequencing. Fecal short-chain fatty acids (SCFAs) and fecal and serum lipopolysaccharide (LPS) were determined. An antibiotic-ablated model was established to confirm the role of the gut microbiota in the actions of EMPA.ResultsEMPA reduced the elevation of blood glucose and UACR caused by HFD/STZ. It inhibited the thickening of the colonic crypt and restored goblet cells and the expressions of ZO-1 and Occludin. The 16S rRNA sequencing showed that the diversity of gut microbiota was reduced after HFD/STZ treatment, while it was restored after EMPA treatment. The LPS-producing bacteria, Oscillibacter, and the SCFA-producing bacteria, Bateroid and Odoribacter, were changed after EMPA administration. The therapeutic effects of EMPA on ABX-treated mice were reduced. Meanwhile, the level of fecal SCFAs was decreased, while the levels of fecal and serum LPS were elevated, in T2DM mice, and they were negated by the administration of EMPA.ConclusionEMPA ameliorates T2DM-related DN via altering the gut microbiota, especially reducing LPS-producing bacteria and increasing SCFA-producing bacteria.     

Effect of Metformin on Metabolic Improvement and Gut Microbiota

Metformin is commonly used as the first line of medication for the treatment of metabolic syndromes, such as obesity and type 2 diabetes (T2D). Recently, metformin-induced changes in the gut microbiota have been reported; however, the relationship between metformin treatment and the gut microbiota remains unclear. In this study, the composition of the gut microbiota was investigated using a mouse model of high-fat-diet (HFD)-induced obesity with and without metformin treatment. As expected, metformin treatment improved markers of metabolic disorders, including serum glucose levels, body weight, and total cholesterol levels. Moreover, Akkermansia muciniphila (12.44% ± 5.26%) and Clostridium cocleatum (0.10% ± 0.09%) abundances increased significantly after metformin treatment of mice on the HFD. The relative abundance of A. muciniphila in the fecal microbiota was also found to increase in brain heart infusion (BHI) medium supplemented with metformin in vitro. In addition to the changes in the microbiota associated with metformin treatment, when other influences were controlled for, a total of 18 KEGG metabolic pathways (including those for sphingolipid and fatty acid metabolism) were significantly upregulated in the gut microbiota during metformin treatment of mice on an HFD. Our results demonstrate that the gut microbiota and their metabolic pathways are influenced by metformin treatment.     

A high-fat diet and high-fat and high-cholesterol diet may affect glucose and lipid metabolism differentially through gut microbiota in mice

This study was conducted to investigate the effects of a high-fat diet (HFD) and high-fat and high-cholesterol diet (HFHCD) on glucose and lipid metabolism and on the intestinal microbiota of the host animal. A total of 30 four-week-old female C57BL/6 mice were randomly divided into three groups (n=10) and fed with a normal diet (ND), HFD, or HFHCD for 12 weeks, respectively. The HFD significantly increased body weight and visceral adipose accumulation and partly lowered oral glucose tolerance compared with the ND and HFHCD. The HFHCD increased liver weight, liver fat infiltration, liver triglycerides, and liver total cholesterol compared with the ND and HFD. Moreover, it increased serum high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol compared with the ND and HFD and upregulated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase significantly. The HFHCD also significantly decreased the α-diversity of the fecal bacteria of the mice, to a greater extent than the HFD. The composition of fecal bacteria among the three groups was apparently different. Compared with the HFHCD-fed mice, the HFD-fed mice had more Oscillospira, Odoribacter, Bacteroides, and [Prevotella], but less [Ruminococcus] and Akkermansia. Cecal short-chain fatty acids were significantly decreased after the mice were fed the HFD or HFHCD for 12 weeks. Our findings indicate that an HFD and HFHCD can alter the glucose and lipid metabolism of the host animal differentially; modifications of intestinal microbiota and their metabolites may be an important underlying mechanism.     

The development and ecology of the Japanese macaque gut microbiome from weaning to early adolescence in association with diet

Previously we have shown that the Japanese macaque gut microbiome differs not by obesity per se, but rather in association with high‐fat diet (HFD) feeding. This held true for both pregnant dams, as well as their 1‐year‐old offspring, even when weaned onto a control diet. Here we aimed to examine the stability of the gut microbiome over time and in response to maternal and postweaning HFD feeding from 6 months of age, and at 1 and 3 years of age. In both cross‐sectional and longitudinal specimens, we performed analysis of the V4 hypervariable region of the 16S rRNA gene on anus swabs collected from pregnant dams and their juveniles at age 6 months to 3 years (n = 55). Extracted microbial DNA was subjected to 16S‐amplicon‐based metagenomic sequencing on the Illumina MiSeq platform. We initially identified 272 unique bacterial genera, and multidimensional scaling revealed samples to cluster by age and diet exposures. Dirichlet multinomial mixture modeling of microbiota abundances enabled identification of two predominant enterotypes to which samples sorted, characterized primarily by Treponema abundance, or lack thereof. Approximating the time of initial weaning (6 months), the Japanese macaque offspring microbiome underwent a significant state type transition which stabilized from 1 to 3 years of age. However, we also found the low abundance Treponema enterotype to be strongly associated with HFD exposure, be it during gestation/lactation or in the postweaning interval. Examination of taxonomic co‐occurrences revealed samples within the low Treponema cluster were relatively permissive (allowing for increased interactions between microbiota) whereas samples within the high Treponema cluster were relatively exclusionary (suggesting decreased interactions amongst microbiota). Taken together, these findings suggest that Treponemes are keystone species in the developing gut microbiome of the gut, and susceptible to HFD feeding in their relative abundance.     

Modulation of gut microbiota contributes to curcumin-mediated attenuation of hepatic steatosis in rats

BackgroundStructural disruption of gut microbiota contributes to the development of non-alcoholic fatty liver disease (NAFLD) and modulating the gut microbiota represents a novel strategy for NAFLD prevention. Although previous studies have demonstrated that curcumin alleviates hepatic steatosis, its effect on the gut microbiota modulation has not been investigated.MethodsNext generation sequencing and multivariate analysis were utilized to evaluate the structural changes of gut microbiota in a NAFLD rat model induced by high fat-diet (HFD) feeding.ResultsWe found that curcumin attenuated hepatic ectopic fat deposition, improved intestinal barrier integrity, and alleviated metabolic endotoxemia in HFD-fed rats. More importantly, curcumin dramatically shifted the overall structure of the HFD-disrupted gut microbiota toward that of lean rats fed a normal diet and altered the gut microbial composition. The abundances of 110 operational taxonomic units (OTUs) were altered by curcumin. Seventy-six altered OTUs were significantly correlated with one or more hepatic steatosis associated parameters and designated ‘functionally relevant phylotypes’. Thirty-six of the 47 functionally relevant OTUs that were positively correlated with hepatic steatosis associated parameters were reduced by curcumin.ConclusionThese results indicate that curcumin alleviates hepatic steatosis in part through stain-specific impacts on hepatic steatosis associated phylotypes of gut microbiota in rats.General significanceCompounds with antimicrobial activities should be further investigated as novel adjunctive therapies for NAFLD.     

Membrane filter method to study the effects of Lactobacillus acidophilus and Bifidobacterium longum on fecal microbiota

A large number of commensal bacteria inhabit the intestinal tract, and interbacterial communication among gut microbiota is thought to occur. In order to analyze symbiotic relationships between probiotic strains and the gut microbiota, a ring with a membrane filter fitted to the bottom was used for in vitro investigations. Test strains comprising probiotic nitto strains (Lactobacillus acidophilus NT and Bifidobacterium longum NT) and type strains (L. acidophilus JCM1132^T and B. longum JCM1217^T) were obtained from diluted fecal samples using the membrane filter to simulate interbacterial communication. Bifidobacterium spp., Streptococcus pasteurianus, Collinsella aerofaciens, and Clostridium spp. were the most abundant gut bacteria detected before coculture with the test strains. Results of the coculture experiments indicated that the test strains significantly promote the growth of Ruminococcus gnavus, Ruminococcus torques, and Veillonella spp. and inhibit the growth of Sutterella wadsworthensis. Differences in the relative abundances of gut bacterial strains were furthermore observed after coculture of the fecal samples with each test strain. Bifidobacterium spp., which was detected as the dominant strain in the fecal samples, was found to be unaffected by coculture with the test strains. In the present study, interbacterial communication using bacterial metabolites between the test strains and the gut microbiota was demonstrated by the coculture technique. The detailed mechanisms and effects of the complex interbacterial communications that occur among the gut microbiota are, however, still unclear. Further investigation of these relationships by coculture of several fecal samples with probiotic strains is urgently required.