scholarly journals A standardized gnotobiotic mouse model harboring a minimal 15-member mouse gut microbiota recapitulates SOPF/SPF phenotypes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marion Darnaud ◽  
Filipe De Vadder ◽  
Pascaline Bogeat ◽  
Lilia Boucinha ◽  
Anne-Laure Bulteau ◽  
...  
Keyword(s):  
Mouse Model ◽  
Gut Microbiota ◽  
Opportunistic Pathogen ◽  
Fecal Microbiota ◽  
Preclinical Studies ◽  
Microbiota Composition ◽  
Laboratory Mice ◽  
Confounding Effect ◽  
Health And Disease ◽  
Mouse Gut Microbiota

AbstractMus musculus is the classic mammalian model for biomedical research. Despite global efforts to standardize breeding and experimental procedures, the undefined composition and interindividual diversity of the microbiota of laboratory mice remains a limitation. In an attempt to standardize the gut microbiome in preclinical mouse studies, here we report the development of a simplified mouse microbiota composed of 15 strains from 7 of the 20 most prevalent bacterial families representative of the fecal microbiota of C57BL/6J Specific (and Opportunistic) Pathogen-Free (SPF/SOPF) animals and the derivation of a standardized gnotobiotic mouse model called GM15. GM15 recapitulates extensively the functionalities found in the C57BL/6J SOPF microbiota metagenome, and GM15 animals are phenotypically similar to SOPF or SPF animals in two different facilities. They are also less sensitive to the deleterious effects of post-weaning malnutrition. In this work, we show that the GM15 model provides increased reproducibility and robustness of preclinical studies by limiting the confounding effect of fluctuation in microbiota composition, and offers opportunities for research focused on how the microbiota shapes host physiology in health and disease.

scholarly journals A standardized gnotobiotic mouse model harboring a minimal 15-member mouse gut microbiota recapitulates SOPF phenotype

2019 ◽  
Author(s):  
Marion Darnaud ◽  
Filipe De Vadder ◽  
Pascaline Bogeat ◽  
Lilia Boucinha ◽  
Anne-Laure Bulteau ◽  
...  
Keyword(s):  
Mouse Model ◽  
Gut Microbiota ◽  
Biomedical Research ◽  
Laboratory Mouse ◽  
Fecal Microbiota ◽  
Preclinical Studies ◽  
Microbiota Composition ◽  
Confounding Effect ◽  
Composition Fluctuation ◽  
Mouse Gut Microbiota

AbstractMus musculus is the classic mammalian model for biomedical research. Despite global efforts in standardizing breeding and experimental procedures, the undefined nature and inter-individual diversity of laboratory mouse microbiota remains a limitation. In an attempt to standardize preclinical studies, we have developed a simplified mouse microbiota composed of 15 strains from 7 of the 20 most prevalent bacterial families representative of the fecal microbiota found in specific opportunistic- and pathogen-free (SOPF) C57BL/6J animals and derived a standardized gnotobiotic mouse model called GM15. GM15 recapitulates extensively the functionalities found in C57BL/6J SOPF microbiota metagenome and GM15 animals are phenotypically similar to SOPF. They even perform better in a model of post-weaning malnutrition. The GM15 model ensures an increased reproducibility and robustness of preclinical studies by limiting the confounding effect of microbiota composition fluctuation and offers new possibilities for research focusing on how the microbiota shapes host physiology in health and diseases.

scholarly journals Draft Genome Sequences of 15 Bacterial Species Constituting the Stable Defined Intestinal Microbiota of the GM15 Gnotobiotic Mouse Model

2020 ◽  
Vol 9 (35) ◽  
Author(s):  
Céline Elie ◽  
Alban Mathieu ◽  
Adrien Saliou ◽  
Adrien Villain ◽  
Marion Darnaud ◽  
...  
Keyword(s):  
Mouse Model ◽  
Intestinal Microbiota ◽  
Bacterial Species ◽  
Draft Genome ◽  
Opportunistic Pathogen ◽  
Bacterial Consortium ◽  
Preclinical Studies ◽  
Genome Sequences ◽  
Confounding Effect ◽  
Composition Fluctuation

ABSTRACT The GM15 community is a bacterial consortium used to generate a novel standardized mouse model with a simplified controlled intestinal microbiota recapitulating the specific opportunistic pathogen-free (SOPF) mouse phenotype and the potential to ensure an increased reproducibility and robustness of preclinical studies by limiting the confounding effect of microbiota composition fluctuation.

Non-uinform gut microbiota alteration patterns associated with therapeutic outcomes in an Alzheimer's disease animal model

2019 ◽  
Author(s):  
Min Wang ◽  
William Kwame Amakye ◽  
Jianing Cao ◽  
Congcong Gong ◽  
Xiaoyu Sun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Therapeutic Outcomes ◽  
Targeted Treatments ◽  
Amyloid Aβ

Abstract Background: Dysbiosis of gut microbiota is associated with the progression of beta-amyloid (Aβ) pathology in Alzheimer’s disease (AD). We aimed to identify uniform Aβ-responsible gut microbiota status as possible guideline for gut microbiota manipulation and the prediction of outcomes of microbiota targeted treatments. Six months old APP/PS1 mice from the same genetic background, housing and feeding conditions were then daily gavage with Metformin, peptides WN5 or PW5 to manipulate the gut microbiota for 12 weeks. Aβ pathology and gut microbiota were then explored and compared. Results: Fecal microbiota transplantation (FMT) from a 16 month old APP/PS1 mouse reconstituted the gut microbiota towards the donor and increased Aβ pathology in APP/PS1 mouse model. Metformin, peptides WN5 and PW5 all attenuated Aβ-plaque formation in APP/PS1 mouse model but each was associated with distinct gut microbiota status. No uniform gut microbiota pattern associated with Aβ pathology was found among different gut microbiota-targeted treatments. Conclusion: We found no uniform gut microbiota status associated with Aβ pathology suggesting gut microbiota status is not a suitable biomarker for AD diagnosis and treatment predictions. Alteration of gut microbiota in itself may not be sufficiently directly related to functional outcomes and might only be a shadow of deeper molecular mechanisms not fully understood. The findings here strongly suggested that the significance of gut microbiota alteration in disease pathology and treatment may have so far been over claimed and that interpretation of gut microbiota data should be done with utmost caution.

scholarly journals Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Lorena Coretti ◽  
Claudia Cristiano ◽  
Ermanno Florio ◽  
Giovanni Scala ◽  
Adriano Lama ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Microbiota Composition ◽  
Btbr Mouse ◽  
Gut Microbiota Composition

scholarly journals Fecal Microbiota Transplantation Controls Murine Chronic Intestinal Inflammation by Modulating Immune Cell Functions and Gut Microbiota Composition

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 517 ◽  
Author(s):  
Claudia Burrello ◽  
Maria Rita Giuffrè ◽  
Angeli Dominique Macandog ◽  
Angelica Diaz-Basabe ◽  
Fulvia Milena Cribiù ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Immune Cells ◽  
Intestinal Inflammation ◽  
Fecal Microbiota Transplantation ◽  
Experimental Colitis ◽  
Fecal Microbiota ◽  
Microbiota Composition ◽  
Chronic Intestinal Inflammation ◽  
Gut Microbiota Composition

Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.

scholarly journals Comparative Analysis of Fecal Microbiota Composition Between Rheumatoid Arthritis and Osteoarthritis Patients

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 748 ◽  
Author(s):  
Jin-Young Lee ◽  
Mohamed Mannaa ◽  
Yunkyung Kim ◽  
Jehun Kim ◽  
Geun-Tae Kim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Amplicon Sequencing ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Stool Samples ◽  
Gut Microbiota Composition

The aim of this study was to investigate differences between the gut microbiota composition in patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA). Stool samples from nine RA patients and nine OA patients were collected, and DNA was extracted. The gut microbiome was assessed using 16S rRNA gene amplicon sequencing. The structures and differences in the gut microbiome between RA and OA were analyzed. The analysis of diversity revealed no differences in the complexity of samples. The RA group had a lower Bacteroidetes: Firmicutes ratio than did the OA group. Lactobacilli and Prevotella, particularly Prevotella copri, were more abundant in the RA than in the OA group, although these differences were not statistically significant. The relative abundance of Bacteroides and Bifidobacterium was lower in the RA group. At the species level, the abundance of certain bacterial species was significantly lower in the RA group, such as Fusicatenibacter saccharivorans, Dialister invisus, Clostridium leptum, Ruthenibacterium lactatiformans, Anaerotruncus colihominis, Bacteroides faecichinchillae, Harryflintia acetispora, Bacteroides acidifaciens, and Christensenella minuta. The microbial properties of the gut differed between RA and OA patients, and the RA dysbiosis revealed results similar to those of other autoimmune diseases, suggesting that a specific gut microbiota pattern is related to autoimmunity.

scholarly journals Gut Microbiota Composition and Metabolomic Profiles of Wild and Captive Chinese Monals (Lophophorus lhuysii) 

2020 ◽  
Author(s):  
Dandan Jiang ◽  
Xin He ◽  
Marc Valitutto ◽  
Li Chen ◽  
Qin Xu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Performance ◽  
Bird Species ◽  
Alpha Diversity ◽  
Integrated Approach ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Metabolomic Profile ◽  
Gut Microbiota Composition

Abstract Background：The Chinese monal (Lophophorus lhuysii) is an endangered bird species, with a wild population restricted to the mountains of southwest China, and only one known captive population in the world. We investigated the fecal microbiota and metabolome of wild and captive Chinese monals to explore differences and similarities in nutritional status and digestive characteristics. An integrated approach combining 16S ribosomal RNA (16S rRNA) gene sequencing and ultra-high performance liquid chromatography (UHPLC) based metabolomics were used to examine the fecal microbiota composition and the metabolomic profile of Chinese monals. Results: The results showed that the alpha diversity of gut microbes in the wild group were significantly higher than that in the captive group and the core bacterial taxa in the two groups showed remarkable differences at phylum, class, order, and family levels. Metabolomic profiling also revealed differences, mainly related to galactose, starch and sucrose metabolism, fatty acid, bile acid biosynthesis and bile secretion. Furthermore, strong correlations of metabolite types and bacterial genus were detected. Conclusions: There were remarkable differences in the gut microbiota composition and metabolomic profile between wild and captive Chinese monals. This study has established a baseline for a normal gut microbiota and metabolomic profile for wild Chinese monals, thus allowing us to evaluate if differences seen in captive organisms have an impact on their overall health and reproduction.

scholarly journals Shifts in the gut microbiota structure caused by Helicobacter pylori eradication therapy

2018 ◽  
Author(s):  
Evgenii I. Olekhnovich ◽  
Alexander I. Manolov ◽  
Nikita A. Prianichniikov ◽  
Andrei E. Samoilov ◽  
Maja V. Malakhova ◽  
...  
Keyword(s):  
Duodenal Ulcer ◽  
Antibiotic Resistance ◽  
Gut Microbiota ◽  
Eradication Therapy ◽  
Microbiota Composition ◽  
Human Gut ◽  
Metabolic Potential ◽  
Health And Disease ◽  
Gut Microbiota Composition ◽  
Microbiota Structure

AbstractThe human gut microbiome plays an important role both in health and disease. The use of antibiotics can alter gut microbiota composition, which can cause complications of various kinds. Here we report a whole genome sequencing metagenomic study of the intestinal microbiota changes caused by Helicobacter pylori eradication therapy. We have found the decrease in taxonomic alpha-diversity due to the therapy. The changes observed were more extensive for patients with duodenal ulcer and female ones. As well across the patients under the therapy we have detected the shifts in the metabolic potential and resistome. Seven KEGG pathways associated with quorum sensing, genetic Information processing and environmental Information processing were increased, while metabolic pathways related with metabolism of cofactors and vitamins and glycan biosynthesis and metabolism decreased. Changes in the resistome profile have also been identified. We observed perturbations in intraspecies structures, which were higher in group of patients under the therapy than in control group of people without treatment. The Eubacterium rectale pangenome extracted from metagenomic data were changed. We also isolated and sequenced Enterococcus faecium strains from two patients before and after eradication therapy. After the therapy this bacterium increased as the antibiotic resistance in vitro, as well the number of ARGs to macrolides and tetracyclines and metagenomic relative abundance in comparison with strains before therapy. In summary, microbial community demonstrated shift to reduce metabolic potential and to increased mechanisms, which mediate more survival condition through intraspecies perturbations.ImportanceThe human gut microbiome plays an important role both in health and disease. The use of antibiotics can alter gut microbiota composition, which can cause complications of various kinds. H. pylori eradication therapy causes multiple shifts and alterations (including intraspecies changes) of the intestinal microbiota structure and leads to the accumulation of genes which determine resistance to macrolides. Since these changes are not the same for patients with various diseases, patients with duodenal ulcer may be further paid special attention for reducing side effects, such as antibiotic-induced dysbiosis. Also, study of antibiotic treatment in terms of its impact upon the human gut microbiota allows shedding light on of the complex processes that cause accumulation and spread of antibiotic resistance. An identification and understanding of these complicated processes may help to constrain antibiotic resistance spread, which is of great importance for human health care.

scholarly journals Fecal Supernatant from Adult with Autism Spectrum Disorder Alters Digestive Functions, Intestinal Epithelial Barrier, and Enteric Nervous System

2021 ◽  
Vol 9 (8) ◽  
pp. 1723
Author(s):  
Jacques Gonzales ◽  
Justine Marchix ◽  
Laetitia Aymeric ◽  
Catherine Le Berre-Scoul ◽  
Johanna Zoppi ◽  
...  
Keyword(s):  
Nervous System ◽  
Gut Microbiota ◽  
Enteric Nervous System ◽  
Fecal Microbiota ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Rrna Gene ◽  
Intestinal Epithelial ◽  
Microbiota Composition ◽  
Α Diversity

Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders defined by impaired social interactions and communication with repetitive behaviors, activities, or interests. Gastrointestinal (GI) disturbances and gut microbiota dysbiosis are frequently associated with ASD in childhood. However, it is not known whether microbiota dysbiosis in ASD patients also occurs in adulthood. Further, the consequences of altered gut microbiota on digestive functions and the enteric nervous system (ENS) remain unexplored. Therefore, we studied, in mice, the ability offecal supernatant (FS) from adult ASD patients to induce GI dysfunctions and ENS remodeling. First, the analyses of the fecal microbiota composition in adult ASD patients indicated a reduced α-diversity and increased abundance of three bacterial 16S rRNA gene amplicon sequence variants compared to healthy controls (HC). The transfer of FS from ASD patients (FS–ASD) to mice decreased colonic barrier permeability by 29% and 58% compared to FS–HC for paracellular and transcellular permeability, respectively. These effects are associated with the reduced expression of the tight junction proteins JAM-A, ZO-2, cingulin, and proinflammatory cytokines TNFα and IL1β. In addition, the expression of glial and neuronal molecules was reduced by FS–ASD as compared to FS-HC in particular for those involved in neuronal connectivity (βIII-tubulin and synapsin decreased by 31% and 67%, respectively). Our data suggest that changes in microbiota composition in ASD may contribute to GI alterations, and in part, via ENS remodeling.

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