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Transfer of gut microbiota from lean and obese mice to antibiotic-treated mice.

ABSTRACT: Transferring gut microbiota from one individual to another may enable researchers to "humanize" the gut of animal models and transfer phenotypes between species. To date, most studies of gut microbiota transfer are performed in germ-free mice. In the studies presented, it was tested whether an antibiotic treatment approach could be used instead. C57BL/6 mice were treated with ampicillin prior to inoculation at weaning or eight weeks of age with gut microbiota from lean or obese donors. The gut microbiota and clinical parameters of the recipients was characterized one and six weeks after inoculation. The results demonstrate, that the donor gut microbiota was introduced, established, and changed the gut microbiota of the recipients. Six weeks after inoculation, the differences persisted, however alteration of the gut microbiota occurred with time within the groups. The clinical parameters of the donor phenotype were partly transmissible from obese to lean mice, in particularly β cell hyperactivity in the obese recipients. Thus, a successful inoculation of gut microbiota was not age dependent in order for the microbes to colonize, and transferring different microbial compositions to conventional antibiotic-treated mice was possible at least for a time period during which the microbiota may permanently modulate important host functions.

SUBMITTER: Ellekilde M

PROVIDER: S-EPMC4118149 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Prolonged transfer of feces from the lean mice modulates gut microbiota in obese mice.

Project description:BackgroundTransplanting a fecal sample from lean, healthy donors to obese recipients has been shown to improve metabolic syndrome symptoms. We therefore examined the gut microbiota in mice after administering a long-term, high-fat diet (HFD) supplemented with feces from lean mice through the fecal-oral route.MethodsC57BL6/W mice were allowed to adapt to a non-specific pathogen free (SFP) environment for 2 weeks before being divided into three groups of 16 animals. Animals were fed for 28 weeks with a normal diet (ND), HFD or HFD supplemented with feces from ND-fed mice (HFDS). The composition of colonizing bacteria was evaluated in droppings collected under SPF conditions at the beginning of the study and at 12 and 28 weeks using an 16S Metagenomics Kit on Ion PGM sequencer.ResultsHFD and HFDS-fed mice attained (p < 0.05) greater body weights by weeks 6 and 5, respectively. HFDS-fed mice gained more weight than HFD-fed mice by week 25. Both species diversity and richness indices increased with time in HFDS mice only.ConclusionsProlonged HFD-fed mice supplementation with feces from lean mice altered bacteria species diversity and richness, accelerated the onset of obesity, and caused increased weight gain in the later weeks of the HFD regimen.

| S-EPMC4995824 | biostudies-literature

Responses of gut microbiota to diet composition and weight loss in lean and obese mice.

Project description:Maintenance of a reduced body weight is accompanied by a decrease in energy expenditure beyond that accounted for by reduced body mass and composition, as well as by an increased drive to eat. These effects appear to be due--in part--to reductions in circulating leptin concentrations due to loss of body fat. Gut microbiota have been implicated in the regulation of body weight. The effects of weight loss on qualitative aspects of gut microbiota have been studied in humans and mice, but these studies have been confounded by concurrent changes in diet composition, which influence microbial community composition. We studied the impact of 20% weight loss on the microbiota of diet-induced obese (DIO: 60% calories fat) mice on a high-fat diet (HFD). Weight-reduced DIO (DIO-WR) mice had the same body weight and composition as control (CON) ad-libitum (AL) fed mice being fed a control diet (10% calories fat), allowing a direct comparison of diet and weight-perturbation effects. Microbial community composition was assessed by pyrosequencing 16S rRNA genes derived from the ceca of sacrificed animals. There was a strong effect of diet composition on the diversity and composition of the microbiota. The relative abundance of specific members of the microbiota was correlated with circulating leptin concentrations and gene expression levels of inflammation markers in subcutaneous white adipose tissue in all mice. Together, these results suggest that both host adiposity and diet composition impact microbiota composition, possibly through leptin-mediated regulation of mucus production and/or inflammatory processes that alter the gut habitat.

| S-EPMC3871199 | biostudies-literature

Assessment of gut microbiota populations in lean and obese Zucker rats.

Project description:Obesity has been on the rise in the US and worldwide for the last several decades. Obesity has been associated with chronic disease development, such as certain types of cancer, type 2 diabetes, cardiovascular disease, and liver diseases. Previously, we reported that obesity promotes DMBA-induced mammary tumor development using the obese Zucker rat model. The intestinal microbiota is composed of a diverse population of obligate and facultative anaerobic microorganisms, and these organisms carry out a broad range of metabolic activities. Obesity has been linked to changes in the intestinal microbiota, but the composition of the bacterial populations in lean and obese Zucker rats has not been carefully studied. Therefore, the objective of this study was to determine the effects of obesity on the gut microbiota in this model. Lean and obese female Zucker rats (n = 16) were fed an AIN-93G-like diet for 8 weeks. Rats were weighed twice weekly, and fecal samples were collected at the beginning and end of the experiment. 16S rRNA gene sequencing was used to evaluate the composition of the fecal bacterial populations. At the outset of the study, the lean rats exhibited much lower ratios of the Firmicutes to Bacteroidetes phyla than the obese rats, but after 60 days, this ratio in the lean rats exceeded that of the obese. This shift was associated with reductions in the Bacteroidaceae, S24-7 and Paraprevotellaceae families in the lean rats. Obese rats also showed increased levels of the genus Akkermansia at day 60. PCoA plots of beta diversity showed clustering of the different test groups, indicating clear differences in intestinal microbiota populations associated with both the time point of the study and the lean or obese status in the Zucker rat model for obesity.

| S-EPMC5509373 | biostudies-literature

Orlistat-Induced Gut Microbiota Modification in Obese Mice.

Project description:IntroductionAccumulating evidence has indicated that alterations of gut microbiota have been involved in various metabolic diseases. Orlistat, a reversible inhibitor of pancreatic and gastric lipase, has beneficial effects on weight loss and metabolism. However, the effect of orlistat on the composition of gut microbiota remains unclear.ObjectiveWe aimed to explore the effect of orlistat on gut microbiota in high-fat diet (HFD) fed C57BL/6J obese mice.MethodsC57BL/6J mice were randomly divided into three groups: control (NCD), HFD, and HFD?+?orlistat (ORL). Mice in the NCD group were fed chow diet, while the other groups were fed HFD for 6 months, and orlistat was added in the final 3 months in the HFD?+?ORL group. After sacrifice, body weight and metabolic parameters were assessed, and the gut microbial composition was analyzed by 16S rRNA gene sequencing.ResultsOrlistat treatment exerted beneficial effects on body weight, plasma cholesterol, and glucose tolerance. Meanwhile, orlistat treatment modified the gut microbiota, presenting as reduced total microbial abundance and obvious upregulated bacteria. Moreover, the upregulated bacteria correlated with several metabolic pathways.ConclusionsOrlistat may exert beneficial effects on body weight and glucose tolerance through modifying the composition of gut microbiota.

| S-EPMC7168719 | biostudies-literature

Gut microbiota impairs insulin clearance in obese mice.

Project description:ObjectiveHyperinsulinemia can be both a cause and consequence of obesity and insulin resistance. Hyperinsulinemia can result from increased insulin secretion and/or reduced insulin clearance. While many studies have focused on mechanisms triggering insulin secretion during obesity, the triggers for changes in insulin clearance during obesity are less defined. In this study, we investigated the role of the microbiota in regulating insulin clearance during diet-induced obesity.MethodsBlood glucose and insulin clearance were tested in conventional male mice treated with antibiotics and germ-free mice colonized with microbes from mice that were fed a control (chow) diet or an obesogenic high-fat diet (HFD). The composition of the fecal microbiota was analyzed using 16S rRNA sequencing.ResultsShort-term HFD feeding and aging did not alter insulin clearance in the mice. Oral antibiotics mitigated impaired blood insulin clearance in the mice fed an HFD for 12 weeks or longer. Germ-free mice colonized with microbes from HFD-fed donor mice had impaired insulin but not C-peptide clearance. Microbe-transmissible insulin clearance impairment was only observed in germ-free mice after more than 6 weeks post-colonization upon HFD feeding. Five bacterial taxa predicted >90% of the variance in insulin clearance. Mechanistically, impaired insulin clearance was associated with lower levels of hepatic Ceacam-1 but increased liver and skeletal muscle insulin-degrading enzyme (IDE) activity.ConclusionsGut microbes regulate insulin clearance during diet-induced obesity. A small cluster of microbes or their metabolites may be targeted for mitigating defects in insulin clearance and hyperinsulinemia during the progression of obesity and type 2 diabetes.

| S-EPMC7522491 | biostudies-literature

Association of the gut microbiota with clinical variables in obese and lean Emirati subjects.

Project description:BackgroundGrowing evidence supports the role of gut microbiota in obesity, yet exact associations remain largely unknown. Specifically, very little is known about this association in the Emirati population.MethodsWe explored differences in gut microbiota composition, particularly the Firmicutes/Bacteroidetes (F/B) ratio, between 43 obese and 31 lean adult Emirate counterparts, and its association with obesity markers, by using V3-V4 regions of 16 S ribosomal RNA gene sequencing data. Furthermore, we collected anthropometric and biochemical data.ResultsThe two major phyla in obese and lean groups were Firmicutes and Bacteroidetes. We observed a significantly lower alpha diversity (Shannon index) in obese subjects and a significant difference in beta diversity and phylum and genus levels between the two groups. The obese group had higher abundances of Verrucomicrobia and Saccharibacteira and lower abundances of Lentisphaerae. Acidaminococcus and Lachnospira were more abundant in obese subjects and positively correlated with adiposity markers. No correlations were found between the gut microbiota and biochemical variables, such as fasting blood sugar, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides.ConclusionWe reveal significant differences in the gut microbiota between obese and lean adult Emiratis and an association between certain microbial genera of the gut microbiota and obesity. A better understanding of the interactions between gut microbes, diet, lifestyle, and health is warranted.

| S-EPMC10481963 | biostudies-literature

Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant.

Project description:Antibiotic treatment can deplete the commensal bacteria of a patient's gut microbiota and, paradoxically, increase their risk of subsequent infections. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), antibiotic administration is essential for optimal clinical outcomes but significantly disrupts intestinal microbiota diversity, leading to loss of many beneficial microbes. Although gut microbiota diversity loss during allo-HSCT is associated with increased mortality, approaches to reestablish depleted commensal bacteria have yet to be developed. We have initiated a randomized, controlled clinical trial of autologous fecal microbiota transplantation (auto-FMT) versus no intervention and have analyzed the intestinal microbiota profiles of 25 allo-HSCT patients (14 who received auto-FMT treatment and 11 control patients who did not). Changes in gut microbiota diversity and composition revealed that the auto-FMT intervention boosted microbial diversity and reestablished the intestinal microbiota composition that the patient had before antibiotic treatment and allo-HSCT. These results demonstrate the potential for fecal sample banking and posttreatment remediation of a patient's gut microbiota after microbiota-depleting antibiotic treatment during allo-HSCT.

| S-EPMC6468978 | biostudies-literature

Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice.

Project description:Antibiotics have long-lasting consequences on the gut microbiota with the potential to impact host physiology and health. However, little is known about the transgenerational impact of an antibiotic-perturbed microbiota. Here we demonstrated that adult pregnant female mice inoculated with a gut microbial community shaped by antibiotic exposure passed on their dysbiotic microbiota to their offspring. This dysbiotic microbiota remained distinct from controls for at least 5 months in the offspring without any continued exposure to antibiotics. By using IL-10 deficient mice, which are genetically susceptible to colitis, we showed mice that received an antibiotic-perturbed gut microbiota from their mothers had increased risk of colitis. Taken together, our findings indicate that the consequences of antibiotic exposure affecting the gut microbiota can extend to a second generation.

2017-12-01 | GSE92623 | GEO

Global profiling of gut microbiota-associated lipid metabolites in antibiotic-treated mice by LC-MS/MS-based analyses.

Project description:We describe a protocol for identifying bacteria-derived lipid metabolites produced in the guts using antibiotic-treated mice, liquid chromatography tandem mass spectrometry-based lipidomics, and feature-based molecular spectrum networking (FBMN). Untargeted lipidomics using the MS-DIAL 4 program provides information on known and unknown complex lipid molecules. The FBMN technique clusters similar MS2 spectra, facilitating the identification of bacterial lipids. Targeted analysis was used as a complementary method to cover oxylipins. Here, we provide details for targeted and untargeted analyses. For complete details on the use and execution of this protocol, please refer to Yasuda et al. (2020).

| S-EPMC8091925 | biostudies-literature

The Gut Microbiota from Lean and Obese Subjects Contribute Differently to the Fermentation of Arabinogalactan and Inulin.

Project description:BackgroundAn aberrant metabolic activity or a compositional alteration of the gut microbiota has been proposed as a factor that makes us more prone to disease. Therefore, we explored the effect of two dietary fibers (arabinogalactan and inulin) on the microbiota from lean and obese subjects during 72 h in vitro fermentation experiments using the validated TNO dynamic in vitro model of the proximal colon: TIM-2. Metabolically, arabinogalactan fermentation showed a higher production of propionate when compared to n-butyrate in the obese microbiota fermentations. In general, lean microbiota produced more n-butyrate from the fermentation of both substrates when compared to the obese microbiota. Furthermore, the obese microbiota extracted more energy from the fermentation of both fibers.ResultsCompositionally, bacteria belonging to Gemmiger, Dorea, Roseburia, Alistipes, Lactobacillus and Bifidobacterium genera were found to be highly abundant or stimulated by the prebiotics in the lean microbiota suggesting a potential role in leanness. Furthermore, a significant correlation between known butyrogenic strains including B. adolescentis, an unclassified Bifidobacterium and F. prausnitzii with this metabolite in the fermentation of inulin in both microbiotas was found.ConclusionsAlthough supplementary in vivo studies are needed, the current study provides more evidence for the consumption of specific ingredients with the aim of modulating the gut microbiota in the context of obesity.

| S-EPMC4943740 | biostudies-literature

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