Consistent alterations of human fecal microbes after transplanted to germ-free mice

AbstractBackgroundFecal microbiota transplant (FMT) of human fecal samples to germ-free (GF) mice is useful for establishing causal relationships between gut microbiota and human phenotypes. However, due to intrinsic differences between human and mouse intestines and distinct diets between the two organisms, replicating human phenotypes in mouse through FMT is not guaranteed; similarly, treatments that are effective in mouse models do not guarantee their success in human either.ResultsIn this study, we aimed to identify human gut microbes that have undergone significant and consistent changes after transplanted to GF mice across multiple experimental settings. By comparing gut microbiota profiles in 1,713 human-mouse pairs, we found strikingly on average <50% of the human gut microbes can be re-established in mice at the species level; among which, more than 1/3 have undergone significant changes (referred as to “variable microbes”), most of which were consistent across multiple human-mouse pairs and experimental settings. Consistently, one-third of human samples had changed their enterotypes, i.e. significant changes in their leading species after FMT. Mice fed with controlled diet showed significant decrease in the enterotype change rate (~25%) as compared those with non-controlled diet (~50%), suggesting a possible solution for rescue. Strikingly, most of the variable microbes have been implicated in human diseases, with some being recognized as causing species.ConclusionsOur results highlighted the challenges of using mouse model in replicating human gut microbiota-associated phenotypes, provided useful information for researchers using mice in their gut microbiota studies and call for additional validations after FMT.

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Clostridioides difficileuses amino acids associated with gut microbial dysbiosis in a subset of patients with diarrhea

Science Translational Medicine ◽

10.1126/scitranslmed.aam7019 ◽

2018 ◽

Vol 10 (464) ◽

pp. eaam7019 ◽

Cited By ~ 43

Author(s):

Eric J. Battaglioli ◽

Vanessa L. Hale ◽

Jun Chen ◽

Patricio Jeraldo ◽

Coral Ruiz-Mojica ◽

...

Keyword(s):

Risk Factors ◽

Amino Acid ◽

Gut Microbiota ◽

Critical Role ◽

Human Gut ◽

Fecal Microbiota Transplant ◽

Germ Free ◽

Human Gut Microbiota ◽

Microbial Dysbiosis ◽

Amino Acid Availability

The gut microbiota plays a critical role in pathogen defense. Studies using antibiotic-treated mice reveal mechanisms that increase susceptibility toClostridioides difficileinfection (CDI), but risk factors associated with CDI in humans extend beyond antibiotic use. Here, we studied the dysbiotic gut microbiota of a subset of patients with diarrhea and modeled the gut microbiota of these patients by fecal transplantation into germ-free mice. When challenged withC. difficile, the germ-free mice transplanted with fecal samples from patients with dysbiotic microbial communities showed increased gut amino acid concentrations and greater susceptibility to CDI. AC. difficilemutant that was unable to use proline as an energy source was unable to robustly infect germ-free mice transplanted with a dysbiotic or healthy human gut microbiota. Prophylactic dietary intervention using a low-proline or low-protein diet in germ-free mice colonized by a dysbiotic human gut microbiota resulted in decreased expansion of wild-typeC. difficileafter challenge, suggesting that amino acid availability might be important for CDI. Furthermore, a prophylactic fecal microbiota transplant in mice with dysbiosis reduced proline availability and protected the mice from CDI. Last, we identified clinical risk factors that could potentially predict gut microbial dysbiosis and thus greater susceptibility to CDI in a retrospective cohort of patients with diarrhea. Identifying at-risk individuals and reducing their susceptibility to CDI through gut microbiota–targeted therapies could be a new approach to preventingC. difficileinfection in susceptible patients.

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High engraftment capacity of frozen ready-to-use human fecal microbiota transplants assessed in germ-free mice

Scientific Reports ◽

10.1038/s41598-021-83638-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Magali Berland ◽

Julie Cadiou ◽

Florence Levenez ◽

Nathalie Galleron ◽

Benoît Quinquis ◽

...

Keyword(s):

Mouse Model ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Fecal Microbiota Transplant ◽

Shotgun Metagenomics ◽

Germ Free ◽

Important Group ◽

Freeze Dried ◽

The Family ◽

Fresh Preparation

AbstractThe number of indications for fecal microbiota transplantation is expected to rise, thus increasing the needs for production of readily available frozen or freeze-dried transplants. Using shotgun metagenomics, we investigated the capacity of two novel human fecal microbiota transplants prepared in maltodextrin-trehalose solutions (abbreviated MD and TR for maltodextrin:trehalose, 3:1, w/w, and trehalose:maltodextrin 3:1, w/w, respectively), to colonize a germ-free born mouse model. Gavage with frozen-thawed MD or TR suspensions gave the taxonomic profiles of mouse feces that best resembled those obtained with the fresh inoculum (Spearman correlations based on relative abundances of metagenomic species around 0.80 and 0.75 for MD and TR respectively), while engraftment capacity of defrosted NaCl transplants most diverged (Spearman correlations around 0.63). Engraftment of members of the family Lachnospiraceae and Ruminoccocaceae was the most challenging in all groups of mice, being improved with MD and TR transplants compared to NaCl, but still lower than with the fresh preparation. Improvement of engraftment of this important group in maintaining health represents a challenge that could benefit from further research on fecal microbiota transplant manufacturing.

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Carrageenan oligosaccharides and their degrading bacteria induce intestinal inflammation in germ-free mouse

10.21203/rs.3.rs-26790/v1 ◽

2020 ◽

Author(s):

Yeshi Yin ◽

Miaomiao Li ◽

Weizhong Gu ◽

Benhua Zeng ◽

Wei Liu ◽

...

Keyword(s):

Inflammatory Response ◽

Gut Microbiota ◽

Fecal Microbiota ◽

Rna Seq ◽

Human Gut ◽

Germ Free ◽

Esi Ms ◽

Human Gut Microbiota ◽

Degrading Bacteria

Abstract Background: Carrageenans (CGNs) are widely used in food and pharmaceutical industries. However, the safety of CGNs is still under debate, because degraded CGNs have been reported to promote an intestinal inflammatory response in animal models. Here, we studied the relationship among CGNs, human gut microbiota, and the host inflammatory response.Methods: TLC was selected for detecting the degradation of KCPs by human gut microbiota in vitro batch fermentation system. PCR-DGGE and real time PCR were used for studying bacterial community. ESI-MS was used for KCPs structure analysis. Hematoxylin-eosin staining (HE), immunohistochemistry (IHC) and RNA-seq were used to evaluated the KCPs on host inflammation response in germ-free mice.Results: Thin-layer chromatography (TLC) data showed that CGNs with a molecular weight (Mw) higher than 100 kDa are not degraded by human fecal microbiota, but low Mw CGNs with an Mw around ~4.5 kDa (KCOs) could be degraded by seven of eight human fecal microbiota samples. KCO degrading B. xylanisolvens was isolated from fecal samples, and PCR-DGGE profiling with band sequencing suggested that B. xylanisolvens was the key KCO degrader in the human gut. Two putative κ-carrageenase genes were identified in the genome sequence of B. xylanisolvens. However, their function on KCO degrading was not verified in vitro. And the sulfate group from KCO is not removed after in vitro degradation by human fecal microbiota, as shown by ESI-MS analysis. The effects of KCO and KCO degrading bacteria on the inflammatory response were investigated in germ-free mice. Increased numbers of P-P38-, CD3a-, and CD79a-positive cells were found in the colon and rectum in mice fed with KCO plus KCO degrading bacteria than in mice fed with only KCO or only B. xylanisolvens and E. coli, as shown by RNA-Seq analysis, HE staining, and IHC. Conclusion: Our data suggested that the presence of KCO degrading bacteria promote the pro-inflammatory effects of CGNs.

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The Role of The Gut Microbiome in Parkinson’s Disease

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/08919887211018268 ◽

2021 ◽

Vol 34 (4) ◽

pp. 253-262

Author(s):

Amy Gallop ◽

James Weagley ◽

Saif-ur-Rahman Paracha ◽

George Grossberg

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Gut Microbiota ◽

Symptom Relief ◽

Antibiotic Use ◽

Fecal Microbiota ◽

Fermented Food ◽

Fecal Microbiota Transplant ◽

Disease States ◽

Cord Blood Transplant

The gut microbiota is known to play a role in various disease states through inflammatory, immune and endocrinologic response. Parkinson’s Disease is of particular interest as gastrointestinal involvement is one of the earlier features seen in this disease. This paper examines the relationship between gut microbiota and Parkinson’s Disease, which has a growing body of literature. Inflammation caused by gut dysbiosis is thought to increase a-synuclein aggregation and worsen motor and neurologic symptoms of Parkinson’s disease. We discuss potential treatment and supplementation to modify the microbiota. Some of these treatments require further research before recommendations can be made, such as cord blood transplant, antibiotic use, immunomodulation and fecal microbiota transplant. Other interventions, such as increasing dietary fiber, polyphenol and fermented food intake, can be made with few risks and may have some benefit for symptom relief and speed of disease progression.

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Depletion of acetate-producing bacteria from the gut microbiota facilitates cognitive impairment through the gut-brain neural mechanism in diabetic mice

Microbiome ◽

10.1186/s40168-021-01088-9 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Hong Zheng ◽

Pengtao Xu ◽

Qiaoying Jiang ◽

Qingqing Xu ◽

Yafei Zheng ◽

...

Keyword(s):

Cognitive Impairment ◽

Gut Microbiota ◽

Cognitive Functions ◽

Neural Mechanism ◽

Fecal Microbiota ◽

Protective Role ◽

Fecal Microbiota Transplant ◽

Memory Impairments ◽

The Impact

Abstract Background Modification of the gut microbiota has been reported to reduce the incidence of type 1 diabetes mellitus (T1D). We hypothesized that the gut microbiota shifts might also have an effect on cognitive functions in T1D. Herein we used a non-absorbable antibiotic vancomycin to modify the gut microbiota in streptozotocin (STZ)-induced T1D mice and studied the impact of microbial changes on cognitive performances in T1D mice and its potential gut-brain neural mechanism. Results We found that vancomycin exposure disrupted the gut microbiome, altered host metabolic phenotypes, and facilitated cognitive impairment in T1D mice. Long-term acetate deficiency due to depletion of acetate-producing bacteria resulted in the reduction of synaptophysin (SYP) in the hippocampus as well as learning and memory impairments. Exogenous acetate supplement or fecal microbiota transplant recovered hippocampal SYP level in vancomycin-treated T1D mice, and this effect was attenuated by vagal inhibition or vagotomy. Conclusions Our results demonstrate the protective role of microbiota metabolite acetate in cognitive functions and suggest long-term acetate deficiency as a risk factor of cognitive decline.

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Combined in vitro colonic fermentation models with immobilized fecal microbiota and cell models to study the human gut microbiota in the healthy and diseased

Journal of Biotechnology ◽

10.1016/j.jbiotec.2010.08.155 ◽

2010 ◽

Vol 150 ◽

pp. 59-59

Author(s):

Christophe Lacroix

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota ◽

Cell Models ◽

Human Gut ◽

Colonic Fermentation ◽

Human Gut Microbiota

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HUMAN GUT MICROBIOTA AND ITS EFFECTS ON HUMAN HEALTH IN NORMAL AND PATHOLOGICAL CONDITIONS

Romanian Medical Journal ◽

10.37897/rmj.2017.3.2 ◽

2017 ◽

Vol 64 (3) ◽

pp. 185-193

Author(s):

Anca Magdalena Munteanu ◽

◽

Raluca Cursaru ◽

Loreta Guja ◽

Simona Carniciu ◽

...

Keyword(s):

Gut Microbiota ◽

New Technologies ◽

Fecal Microbiota Transplantation ◽

Current Knowledge ◽

Gastrointestinal Diseases ◽

Fecal Microbiota ◽

Research Subjects ◽

Human Gut ◽

Human Host ◽

Human Gut Microbiota

The medical research of the last 1-2 decades allows us to look at the human gut microbiota and microbiome as to a structure that can promote health and sometimes initiate disease. It works like an endocrine organ: releasing specific metabolites, using environmental inputs, e.g. diet, or acting through its structural compounds, that signal human host receptors, to finally contributing to the pathogenesis of several gastrointestinal and non-gastrointestinal diseases. The same commensal microbes were found as shapers of the human host response to drugs (cardiovascular, oncology etc.). New technologies played an important role in these achievements, facilitating analysis of the genetic and metabolic profile of this microbial community. Once the inputs, the pathways and a lot of human host receptors were highlighted, the scientists were encouraged to go further into research, in order to develop new pathogenic therapies, targeting the human gut flora. Dual therapies, evolving these “friend microbes”, are another actual research subjects. This review gives an update on the current knowledge in the area of microbiota disbalances under environmental factors, the contribution of gut microbiota and microbiome to the pathogenesis of obesity, obesity associated metabolic disorders and cardiovascular disease, as well as new perspectives in preventing and treating these diseases, with high prevalence in contemporary, economically developed societies. It brings the latest and most relevant evidences relating to: probiotics, prebiotics, polyphenols and fecal microbiota transplantation, dietary nutrient manipulation, microbial as well as human host enzyme manipulation, shaping human responses to currently used drugs, manipulating the gut microbiome by horizontal gene transfer.

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Lupus Gut Microbiota Transplants Cause Autoimmunity and Inflammation

10.1101/2021.08.15.456375 ◽

2021 ◽

Author(s):

Yiyangzi Ma ◽

Ruru Guo ◽

Yiduo Sun ◽

Xin Li ◽

Lun He ◽

...

Keyword(s):

Gut Microbiota ◽

Lupus Erythematosus ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Healthy Controls ◽

Germ Free ◽

Autoimmune Antibodies ◽

Expression Of Genes ◽

Rdna Sequencing

Background: The etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free mice. Results: Compared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to germ free (GF) C57BL/6 mice caused GF mice to develop a series of lupus-like phenotyptic features, which including an increased serum autoimmune antibodies, and imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants. Conclusions: Overall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE.

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

10.21203/rs.2.17297/v1 ◽

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.

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