Composition Of Gut Microbiota In Rats Research Articles

The Effects of 1-Kestose on the Abundance of Inflammation-Related Gene mRNA in Adipose Tissue and the Gut Microbiota Composition in Rats Fed a High-Fat Diet.

Chronic inflammation in adipose tissue is thought to contribute to insulin resistance, which involves the gut microbiota. Our previous studies have demonstrated that ingestion of 1-kestose can alter the gut microbiota composition, increase cecal butyrate levels, and improve insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Additionally, we found that 1-kestose supplementation ameliorated insulin resistance in obese rat models fed a high-fat diet (HFD), although the effects of 1-kestose on the abundance of inflammation-related gene in adipose tissue and gut microbiota composition in these rats were not explored. This study aimed to investigate the impact of 1-kestose on these parameters in HFD-fed rats, compared to OLETF rats. Male Sprague-Dawley rats were divided into two dietary groups, control or HFD, for 19 wk. Each group was further subdivided to receive either tap water or tap water supplemented with 2% (w/v) 1-kestose throughout the study. We evaluated gene expression in adipose tissue, as well as short-chain fatty acids (SCFAs) levels and microbial composition in the cecum contents. 1-Kestose intake restored the increased relative abundance of tumor necrosis factor (Tnf) mRNA in adipose tissue and the reduced level of butyrate in the cecum contents of HFD-fed rats to those observed in control diet-fed rats. Additionally, 1-kestose consumption changed the composition of the gut microbiota, increasing Butyricicoccus spp., decreasing UGC-005 and Streptococcus spp., in the cecum contents of HFD-fed rats. Our findings suggest that 1-kestose supplementation reduces adipose tissue inflammation and increases butyrate levels in the gut of HFD-fed rats, associated with changes in the gut microbiota composition, distinct from those seen in OLETF rats.

Uncovering the mechanisms of Zhubi decoction against rheumatoid arthritis through an integrated study of network pharmacology, metabolomics, and intestinal flora

Ethnopharmacological relevanceZhubi Decoction (ZBD) is a modified formulation derived from the classic traditional Chinese medicine prescription “Er-Xian Decoction” documented in the esteemed “Clinical Manual of Chinese Medical Prescription”. While the utilization of ZBD has exhibited promising clinical outcomes in treating rheumatoid arthritis (RA), the precise bioactive chemical constituents and the underlying mechanisms involved in its therapeutic efficacy remain to be comprehensively determined. Aim of the studyThis study aims to systematically examine ZBD's pharmacological effects and molecular mechanisms for RA alleviation. Materials and methodsUtilizing the collagen-induced arthritis (CIA) rat model, we comprehensively evaluated the anti-rheumatoid arthritis effects of ZBD in vivo through various indices, such as paw edema, arthritis index, ankle diameter, inflammatory cytokine levels, pathological conditions, and micro-CT analysis. The UPLC-MS/MS technique was utilized to analyze the compounds of ZBD. The potential therapeutic targets and signaling pathways of ZBD in the management of RA were predicted using network pharmacology. To analyze comprehensive metabolic profiles and identify underlying metabolic pathways, we conducted a serum-based widely targeted metabolomics analysis utilizing LC-MS technology. Key targets and predicted pathways were further validated using immunofluorescent staining, which integrated findings from serum metabolomics and network pharmacology analysis. Additionally, we analyzed the gut microbiota composition in rats employing 16 S rDNA sequencing and investigated the effects of ZBD on the microbiota of CIA rats through bioinformatics and statistical methods. ResultsZBD exhibited remarkable efficacy in alleviating RA symptoms in CIA rats without notable side effects. This included reduced paw redness and swelling, minimized joint damage, improved the histopathology of cartilage and synovium, mitigated the inflammatory state, and lowered serum concentrations of cytokines TNF-α, IL-1β and IL-6. Notably, the effectiveness of ZBD was comparable to MTX. Network pharmacology analysis revealed inflammation and immunity-related signaling pathways, such as PI3K/AKT, MAPK, IL-17, and TNF signaling pathways, as vital mediators in the effectual mechanisms of ZBD. Immunofluorescence analysis validated ZBD's ability to inhibit PI3K/AKT pathway proteins. Serum metabolomics studies revealed that ZBD modulates 170 differential metabolites, partially restored disrupted metabolic profiles in CIA rats. With a notable impact on amino acids and their metabolites, and lipids and lipid-like molecules. Integrated analysis of metabolomics and network pharmacology identified 6 pivotal metabolite pathways and 3 crucial targets: PTGS2, GSTP1, and ALDH2. Additionally, 16 S rDNA sequencing illuminated that ZBD mitigated gut microbiota dysbiosis in the CIA group, highlighting key genera such as Ligilactobacillus, Prevotella_9, unclassified_Bacilli, and unclassified_rumen_bacterium_JW32. Correlation analysis disclosed a significant link between 47 distinct metabolites and specific bacterial species. ConclusionZBD is a safe and efficacious TCM formulation, demonstrates efficacy in treating RA through its multi-component, multi-target, and multi-pathway mechanisms. The regulation of inflammation and immunity-related signaling pathways constitutes a crucial mechanism of ZBD's efficacy. Furthermore, ZBD modulates host metabolism and intestinal flora. The integrated analysis presents experimental evidence of ZBD for the management of RA.

Chronic triclosan exposure induce impaired glucose tolerance by altering the gut microbiota

Triclosan (TCS) is an antimicrobial compound incorporated into more than 2000 consumer products. This compound is frequently detected in the human body and causes ubiquitous contamination in the environment, thereby raising concerns about its impact on human health and environmental pollution. Here, we demonstrated that 20 weeks’ exposure of TCS drove the development of glucose intolerance by inducing compositional and functional alterations in intestinal microbiota in rats. Fecal-transplantation experiments corroborated the involvement of gut microbiota in TCS-induced glucose-tolerance impairment. 16S rRNA gene-sequencing analysis of cecal contents showed that TCS disrupted the gut microbiota composition in rats and increased the ratio of Firmicutes to Bacteroidetes. Cecal metabolomic analyses detected that TCS altered host metabolic pathways that are linked to host glucose and amino acid metabolism, particularly branched-chain amino acid (BCAA) biosynthesis. BCAA measurement confirmed the increase in serum BCAAs in rats exposed to TCS. Western blot and immunostaining results further confirmed that elevated BCAAs stimulated mTOR, a nutrient-sensing complex, and following IRS-1 serine phosphorylation, resulted in insulin resistance and glucose intolerance. These results suggested that TCS may induce glucose metabolism imbalance by regulating BCAA concentration by remodeling the gut microbiota.

Persistent improvement effects in dietary fibre-deficient constipation by Japanese Kampo medicine Mashiningan involves altered gut microbiota composition in rats

Persistent improvement effects in dietary fibre-deficient constipation by Japanese Kampo medicine Mashiningan involves altered gut microbiota composition in rats

Effect of a diet rich in galactose or fructose, with or without fructooligosaccharides, on gut microbiota composition in rats.

Recent studies suggest that a diet rich in sugars significantly affects the gut microbiota. Adverse metabolic effects of sugars may partly be mediated by alterations of gut microbiota and gut health parameters, but experimental evidence is lacking. Therefore, we investigated the effects of high intake of fructose or galactose, with/without fructooligosaccharides (FOS), on gut microbiota composition in rats and explored the association between gut microbiota and low-grade systemic inflammation. Sprague–Dawley rats (n = 6/group) were fed the following isocaloric diets for 12 weeks (% of the dry weight of the sugars or FOS): (1) starch (control), (2) fructose (50%), (3) galactose (50%), (4) starch+FOS (15%) (FOS control), (5) fructose (50%)+FOS (15%), (6) galactose (50%)+FOS (15%), and (7) starch+olive (negative control). Microbiota composition in the large intestinal content was determined by sequencing amplicons from the 16S rRNA gene; 341F and 805R primers were used to generate amplicons from the V3 and V4 regions. Actinobacteria, Verrucomicrobia, Tenericutes, and Cyanobacteria composition differed between diets. Bifidobacterium was significantly higher in all diet groups where FOS was included. Modest associations between gut microbiota and metabolic factors as well as with gut permeability markers were observed, but no associations between gut microbiota and inflammation markers were observed. We found no coherent effect of galactose or fructose on gut microbiota composition. Added FOS increased Bifidobacterium but did not mitigate potential adverse metabolic effects induced by the sugars. However, gut microbiota composition was associated with several metabolic factors and gut permeability markers which warrant further investigations.

Differences in the gut microbiota composition of rats fed with soybean protein and their derived peptides.

Current studies regarding the effect of different nitrogen sources on gut microbiota have thus far disregarded the ability of probiotics and coliforms to compete for protein. This study aimed to investigate the differences in the utilization of soybean protein (SPro) and its derived peptides (SPep) by the gut microbiota of Sprague Dawley (SD) rats. The SPro and SPep prepared in this study showed extensive SPro molecular weight distribution, while that of SPep was minimal, ranging between 150 and 1000Da and primarily consisting of two to five amino acids. The cecum microflora composition of the rats was determined via 16S rDNA amplicon sequencing, showing that the SPro and SPep significantly increased the abundance and uniformity of the gut microbiota after 35 days of feeding. The Firmicutes/Bacteroidetes (F/B) ratios of the SPep, SPro, and casein groups were 2.49 ± 0.60,2.98 ± 1.12,and 2.59 ± 0.74,respectively. Although the rats fed with SPro and SPep displayed similar gut microbiome structures, SPep significantly promoted Lactobacillus and Phascolarctobacterium growth. The results showed that SPep significantly increased the diversity of the gut microbiota and elevated the probiotic proportion. PRACTICAL APPLICATION: SPro and SPep are two nutritious and high-quality nitrogen sources. The results showed that SPro and SPep regulated the structure of gut microbiota in rats, and the effect of SPep was better. This study provides a theoretical basis for developing SPep functional foods able to regulate gut microbiota and maintain health.

Foxtail millet supplementation improves glucose metabolism and gut microbiota in rats with high-fat diet/streptozotocin-induced diabetes

Foxtail millet (FM) whole grain has received special attention in recent years. To confirm the hypoglycemic effects of FM, we investigated the effects of FM supplementation on glucose metabolism and gut microbiota in rats with high-fat diet/streptozotocin (HFD/STZ)-induced diabetes. Specifically, we fully assessed the blood biochemical profiles, pancreatic histopathology, insulin-glucagon immunofluorescence, short-chain fatty acids, and gut microbiota composition of rats with HFD/STZ-induced diabetes before and after FM supplementation. Results showed that both 30% and 48% FM supplementation significantly decreased concentrations of fasting blood glucose, 60-min blood glucose, and blood triglycerides (P<0.05); additionally, 48% FM supplementation significantly improved blood glucose tolerance and insulin resistance (P<0.05). However, FM supplementation could not effectively repair damage to β-cells over a short period of time. In addition, 4 weeks of 48% FM supplementation siginificantly increased the relative abundance of Bifidobacterium and concentration of butyrate, suggesting that the hypoglycemic effects of FM supplementation might be partially mediated by gut microbiota. Collectively, we found a dose-dependent relationship between FM supplementation and improvement of blood glucose metabolism, but did not find a synergistic effect between FM supplementation and metformin (Met) treatment. Our findings provide further support that consuming more whole-grain FM might be beneficial to individuals suffering from type 2 diabetes.

Gut Microbiota Induced by Pterostilbene and Resveratrol in High-Fat-High-Fructose Fed Rats: Putative Role in Steatohepatitis Onset.

Resveratrol and its 2-methoxy derivative pterostilbene are two phenolic compounds that occur in foodstuffs and feature hepato-protective effects. This study is devoted to analysing and comparing the metabolic effects of pterostilbene and resveratrol on gut microbiota composition in rats displaying NAFLD induced by a diet rich in saturated fat and fructose. The associations among changes induced by both phenolic compounds in liver status and those induced in gut microbiota composition were also analysed. For this purpose, fifty Wistar rats were distributed in five experimental groups: a group of animals fed a standard diet (CC group) and four additional groups fed a high-fat high-fructose diet alone (HFHF group) or supplemented with 15 or 30 mg/kg bw/d of pterostilbene (PT15 and PT30 groups, respectively) or 30 mg/kg bw/d of resveratrol (RSV30 group). The dramatic changes induced by high-fat high-fructose feeding in the gut microbiota were poorly ameliorated by pterostilbene or resveratrol. These results suggest that the specific changes in microbiota composition induced by pterostilbene (increased abundances of Akkermansia and Erysipelatoclostridium, and lowered abundance of Clostridum sensu stricto 1) may not entirely explain the putative preventive effects on steatohepatitis.

The Gut Microbiota of Rats under Experimental Osteoarthritis and Administration of Chondroitin Sulfate and Probiotic

Osteoarthritis is a most widespread chronic degenerative joint disease that causes pain, cartilage deformation, and joint inflammation. Adverse alterations of intestinal microbiota like dysbiosis may lead to metabolic syndrome and inflammation, two important components of osteoarthritis progression. Aim. In this study we investigated the effect of chondroitin sulfate and probiotics on the gut microbiome in monoiodoacetate-induced osteoarthritis model in rats. Methods. The species and quantitative composition of feces were determined using diagnostic media with selective properties. Further identification of isolated microorganisms was carried out according to morphological, tinctorial, physiological and metabolic parameters. The results are presented in the form of lg CFU/g. Results. Induction of osteoarthritis caused significant increasing the number of opportunistic enterobacteria and lactose-negative Escherichia coli against the decreasing of lacto- and bifidobacteria that may indicate a dysbiotic condition. Coadministration of chondroitin sulfate and probiotic bacteria has led to improvement the quantitative composition of the gut microbiota in experimental animals, the numerous of Bifidobacterium, Lactobacillus were increasing against decreasing the quantitative composition of opportunistic microorganisms. Conclusions. Monoiodoacetate-induced osteoarthritis caused dysbiosis of gut in rat. We observed beneficial effect of combined administration of chondroitin sulfate and probiotics on gut microbiota composition in rats with experimental osteoarthritis. Thus, adding of supplements like probiotics to standard treatment of osteoarthritis may have potentials to prevent and treat this disease.

Dietary Alaska pollock protein alters insulin sensitivity and gut microbiota composition in rats

Fish protein is not only nutritional but also promotes health by improving insulin sensitivity and hypercholesterolemia. Few studies have examined the relationship between gut microbiota and the enhanced insulin sensitivity due to the intake of Alaska pollock protein (APP). Hence, we assessed the glycolytic enzyme inhibitory activity of APP in in vitro study and the alteration of blood glucose level in insulin tolerance test (ITT) and glucose tolerance test (GTT) and gut microbiota following APP intake in the in vivo study. In initial experiments, the glycolytic enzyme (α-amylase, α-glucosidase, and sucrase) inhibitory activities of APP and its digest were not drastically altered compared with that of casein and its digests. In further experiments, rats fed an AIN-93G diet containing 20% (w/w) casein or APP for 8 weeks, and the composition of fecal microbiota analyzed by 16S rRNA amplicon sequence analysis. In addition, at 6 and 7 weeks of administration of experimental diet, insulin and glucose tolerance tests were evaluated, respectively. Compared with dietary casein, dietary APP has blood glucose-lowering activity as evident in the ITT and GTT. Moreover, APP group altered the structure of fecal microbiota, and area under the curves of the ITT and GTT and the relative abundance of Blautia, which is associated with glucose metabolism, tended to be positively correlated (P = 0.08 and 0.10, respectively). This study illustrates a novel finding that APP intake could alter the composition of gut microbiota and improve insulin sensitivity. PRACTICAL APPLICATION: Studies in animals and humans have shown that Alaska pollock protein (APP) intake improves insulin sensitivity, allowing the body to utilize blood glucose more effectively, thereby keeping blood sugar levels under control. Microorganisms residing in the human gut are associated with glucose metabolism. This study shows that the relative APP intake alters the composition of these gut microorganisms, more than casein intake and therefore might prevent hyperglycemia and type 2 diabetes.

Investigation of modulating effect of Qingfei Paidu Decoction on host metabolism and gut microbiome in rats

This study is to explore the effect of Qingfei Paidu Decoction(QPD) on the host metabolism and gut microbiome of rats with metabolomics and 16 S rDNA sequencing. Based on 16 S rDNA sequencing of gut microbiome and metabolomics(GC-MS and LC-MS/MS), we systematically studied the serum metabolites profile and gut microbiota composition of rats treated with QPD for continued 5 days by oral gavage. A total of 23 and 43 differential metabolites were identified based on QPD with GC-MS and LC-MS/MS, respectively. The involved metabolic pathways of these differential metabolites included glycerophospholipid metabolism, linoleic acid metabolism, TCA cycle and pyruvate metabolism. Meanwhile, we found that QPD significantly regulated the composition of gut microbiota in rats, such as enriched Romboutsia, Turicibacter, and Clostridium_sensu_stricto_1, and decreased norank_f_Lachnospiraceae. Our current study indicated that short-term intervention of QPD could significantly regulate the host metabolism and gut microbiota composition of rats dose-dependently, suggesting that the clinical efficacy of QPD may be related with the regulation on host metabolism and gut microbiome.

Camellia nitidissima Chi flower extract alleviates obesity and related complications and modulates gut microbiota composition in rats with high-fat-diet-induced obesity.

The aim of this study was to investigate the potential anti-obesity effects of Camellia nitidissima Chi flower extract (Cnfe) by examining its effects in terms of the regulation of lipid levels and modulation of gut microbiota in rats with high-fat-diet-induced obesity. Our results demonstrated that Cnfe significantly decreased weight gain by reducing appetite and decreasing high-fat food intake. Further, Cnfe restored normal lipid metabolism and improved insulin sensitivity and glucose tolerance in rats fed a high-fat diet. Real-time reverse transcription polymerase chain reaction and western blot results showed that Cnfe significantly decreased the expression of genes and proteins involved in adipogenesis and lipogenesis, and upregulated the expression of lipolysis genes. 16S ribosomal RNA sequencing of feces showed that Cnfe dramatically reversed dysbacteriosis in rats with high-fat-diet-induced obesity by decreasing the abundance of Firmicutes and increasing that of Bacteroidetes and Verrucomicrobia at the phylum level. The results demonstrate that Cnfe is a potential anti-obesity prebiotic nutrient that can prevent weight gain, ameliorate obesity-related dyslipidemia and hyperglycemia, inhibit liver fat accumulation, and modulate gut microbiota. © 2020 Society of Chemical Industry.

The effects of desynchronosis on the gut microbiota composition and physiological parameters of rats

BackgroundAll living organisms experience physiological changes regulated by endogenous circadian rhythms. The main factor controlling the circadian clock is the duration of daylight. The aim of this research was to identify the impact of various lighting conditions on physiological parameters and gut microbiota composition in rats. 3 groups of outbred rats were subjected to normal light-dark cycles, darkness and constant lighting.ResultsAfter 1 and 3 months we studied urinary catecholamine levels in rats; indicators of lipid peroxidation and antioxidant activity in the blood; protein levels of BMAL1, CLOCK and THRA in the hypothalamus; composition and functional activity of the gut microbiota. Subjecting the rats to conditions promoting desynchronosis for 3 months caused disruptions in homeostasis.ConclusionsChanging the lighting conditions led to changes in almost all the physiological parameters that we studied. Catecholamines can be regarded as a synchronization super system of split-level circadian oscillators. We established a correlation between hypothalamic levels of Bmal1 and urinary catecholamine concentrations. The magnitude of changes in the GM taxonomic composition was different for LL/LD and DD/LD but the direction of these changes was similar. As for the predicted functional properties of the GM which characterize its metabolic activity, they didn’t change as dramatically as the taxonomic composition. All differences may be viewed as a compensatory reaction to new environmental conditions and the organism has adapted to those conditions.

Exposure to toxic metals triggers unique responses from the rat gut microbiota

Our understanding of the interaction between the gut microbiota and host health has recently improved dramatically. However, the effects of toxic metal exposure on the gut microbiota remain poorly characterized. As this microbiota creates a critical interface between the external environment and the host’s cells, it may play an important role in host outcomes during exposure. We therefore used 16S ribosomal RNA (rRNA) gene sequencing to track changes in the gut microbiota composition of rats exposed to heavy metals. Rats were exposed daily for five days to arsenic, cadmium, cobalt, chromium, nickel, or a vehicle control. Significant changes to microbiota composition were observed in response to high doses of chromium and cobalt, and significant dose-dependent changes were observed in response to arsenic, cadmium and nickel. Many of these perturbations were not uniform across metals. However, bacteria with higher numbers of iron-importing gene orthologs were overly represented after exposure to arsenic and nickel, suggesting some possibility of a shared response. These findings support the utility of the microbiota as a pre-clinical tool for identifying exposures to specific heavy metals. It is also clear that characterizing changes to the functional capabilities of microbiota is critical to understanding responses to metal exposure.

Intake of phytic acid and myo-inositol lowers hepatic lipogenic gene expression and modulates gut microbiota in rats fed a high-sucrose diet.

Dietary phytic acid (PA) was recently reported by our group to suppress hepatic lipogenic gene expression and modulate gut microbiota in rats fed a high-sucrose (HSC) diet. The present study aimed to investigate whether the modulatory effects of PA depend on the dietary carbohydrate source and are attributed to the myo-inositol (MI) ring of PA. Male Sprague-Dawley rats were fed an HSC or a high-starch (HSR) diet with or without 1.02% sodium PA for 12 days. Subsequently, the rats were fed the HSC diet, the HSC diet containing 1.02% sodium PA or an HSC diet containing 0.2% MI for 12 days. The HSC diet significantly increased the hepatic triglyceride (TG) concentration as well as the activity and expression of hepatic lipogenic enzymes compared with the HSR diet. The increases were generally suppressed by dietary PA with a concomitant increase in the fecal and cecal ratios of Lactobacillus spp. In rats fed the HSR diet, PA intake did not substantially affect the factors associated with hepatic lipid metabolism or gut microbiota composition. The effects of MI intake were similar to that of PA intake on hepatic lipogenesis and gut microbiota in rats fed the HSC diet. These results suggest that dietary PA downregulates hepatic lipogenic gene expression and modulates gut microbiota composition in rats fed an HSC diet but not in rats fed an HSR diet. The MI ring of PA may be responsible for the effects of PA intake on hepatic lipogenic gene expression and gut microbiota.

Rye polyphenols and the metabolism of n-3 fatty acids in rats: a dose dependent fatty fish-like effect

As long-chain fatty acids (LCFA) of the n-3 series are critically important for human health, fish consumption has considerably increased in recent decades, resulting in overfishing to respond to the worldwide demand, to an extent that is not sustainable for consumers’ health, fisheries economy, and marine ecology. In a recent study, it has been shown that whole rye (WR) consumption improves blood and liver n-3 LCFA levels and gut microbiota composition in rats compared to refined rye. The present work demonstrates that specific colonic polyphenol metabolites may dose dependently stimulate the synthesis of n-3 LCFA, possibly through their microbial and hepatic metabolites in rats. The intake of plant n-3 alpha-linolenic acid and WR results in a sort of fatty fish-like effect, demonstrating that the n-3 LCFA levels in blood and tissues could be increased without eating marine foods, and therefore without promoting unsustainable overfishing, and without damaging marine ecology.

Fecal excretion of Maillard reaction products and the gut microbiota composition of rats fed with bread crust or bread crumb.

A comparison between the impacts of advanced (Nε-carboxymethyllysine - CML) and terminal (melanoidins) Maillard reaction products from bread on gut microbiota was carried out in this study. Gut microbiota composition as well as fecal excretion of CML from both bread crust and bread crumb, and of melanoidins from bread crust were assessed on a rodent model. Rats were fed with pellets supplemented or not with 13% of bread crust, bread crumb, a fiber-free bread crust model (glucose, starch and gluten heated together) or a fiber-free-melanoidin-free bread model (glucose-starch and gluten heated separately) for four weeks. These model systems were developed to limit the presence of wheat-native dietary fibers such as cellulose, hemicelluloses and lignin. CML and melanoidins in pellets and feces were evaluated by LC/MS-MS and HPLC/fluorescence respectively, and gut microbiota composition was determined by cultivation and molecular approaches. Diets supplemented with crumb or the fiber-free-melanoidin-free model contained respectively 17% and 64% less melanoidins than their respective controls. A higher excretion of melanoidins was observed for rats fed with crust or bread crust model compared to their controls, confirming that melanoidins are in contact with gut microbiota. No impact of diets was observed on Firmicutes, Bacteroidetes and lactic flora. A decrease of enterobacteria was only observed for rats fed with the diet supplemented with the fiber-free bread crust model. Moreover, a significant increase of bifidobacteria numbers in the presence of crust, crumb and both bread models was observed, showing that this bifidogenic effect of bread is not due to the presence of melanoidins or wheat-native dietary fibers.