scholarly journals Fecal Microbiota Transplantation Can Alleviate Gastrointestinal Transit in Rats with High-Fat Diet-Induced Obesity via Regulation of Serotonin Biosynthesis

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Wenjing Sun ◽  
Yan Guo ◽  
Shirong Zhang ◽  
Zhihui Chen ◽  
Kangqi Wu ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Fecal Microbiota Transplantation ◽  
Gastrointestinal Transit ◽  
Fecal Microbiota ◽  
Control Group ◽  
Serotonin Concentration ◽  
Intestinal Contents ◽  
Small Intestinal ◽  
Serotonin Biosynthesis ◽  
Intestinal Serotonin

Aim. We tested the hypothesis that fecal microbiota transplantation (FMT) could regulate the biotransformation of bile acids, such as deoxycholic acid (DCA) and cholic acid (CA), which in turn regulate the biosynthesis of serotonin in the gut and relieve gastrointestinal dysmotility in high-fat diet- (HFD-) induced obesity in rats. Methods. Male Sprague-Dawley rats were randomly divided into the control diet group, HFD group, and HFD-fed with receiving FMT. HFD was fed for 12 weeks. At the end of two-week HFD, FMT was carried out for two weeks. The gastrointestinal transit, serotonin concentration, the expression of tryptophan hydroxylase 1 (TPH1) and serotonin reuptake transporter (SERT), and the levels of bile acids in intestinal contents were examined. Results. Compared with the control group, the gastrointestinal transit and small intestinal serotonin concentration of HFD-fed rats were increased. In HFD-fed rats, TPH1 protein expression was increased significantly, while SERT protein expression was decreased, but not significant. The levels of CA and DCA in intestinal contents were also significantly increased in HFD-fed rats compared with the control group. After HFD-fed rats receiving FMT treatment, the gastrointestinal transit, small intestinal serotonin concentration, and TPH1 expression were decreased, while SERT expression was not affected. Moreover, the levels of CA and DCA in intestinal contents were also decreased. Conclusions. FMT could alleviate small intestinal transit in the HFD-fed rats by regulating the serotonin biosynthesis. In this process, CA and DCA may be related to the regulation of synthesis of serotonin.

scholarly journals Obesity-induced gut microbiota dysbiosis can be ameliorated by fecal microbiota transplantation: a multiomics approach

2019 ◽  
Author(s):  
Maria Guirro ◽  
Andrea Costa ◽  
Andreu Gual-Grau ◽  
Pol Herrero ◽  
Helena Torrell ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Fecal Microbiota Transplantation ◽  
Obese Subject ◽  
Fecal Microbiota ◽  
Obesity Therapy ◽  
Treatment Of Obesity ◽  
And Function ◽  
Hypercaloric Diet ◽  
Gut Microbiota Dysbiosis

AbstractObesity and its comorbidities are currently considered an epidemic, and the involved pathophysiology is well studied. Recently, the gut microbiota has emerged as a new potential therapeutic target for the treatment of obesity. Diet and antibiotics are known to play crucial roles in changes in the microbiota ecosystem and the disruption of its balance; therefore, the manipulation of gut microbiota may represent a strategy for obesity treatment. Fecal microbiota transplantation, during which fecal microbiota from a healthy donor is transplanted to an obese subject, has aroused interest as an effective approach for the treatment of obesity. To determine its success, a multiomics approach was used that combined metagenomics and metaproteomics to study microbiota composition and function.To do this, a study was performed in rats that evaluated the effect of a hypercaloric diet on the gut microbiota, and this was combined with antibiotic treatment to deplete the microbiota before fecal microbiota transplantation to verify its effects on gut microbiota-host homeostasis. Our results showed that a high-fat diet induces changes in microbiota biodiversity and alters its function in the host. Moreover, we found that antibiotics depleted the microbiota enough to reduce its bacterial content. Finally, we assessed the use of fecal microbiota transplantation as an obesity therapy, and we found that it reversed the effects of antibiotics and reestablished the microbiota balance, which restored normal functioning and alleviated microbiota disruption.

scholarly journals Fecal Microbiota Transplantation for Grade IV Steroid Refractory GI-GvHD: Interim Results a Non-randomized, Open-label, Phase 1 Clinical Study

2020 ◽  
Author(s):  
Ye Zhao ◽  
Xue-wei Li ◽  
Yu-jing Zhou ◽  
Xiao Ma ◽  
Feng Chen ◽  
...  
Keyword(s):  
Clinical Study ◽  
Clinical Remission ◽  
Fecal Microbiota Transplantation ◽  
Phase 1 ◽  
Fecal Microbiota ◽  
Control Group ◽  
Open Label ◽  
Open Label Phase ◽  
Steroid Refractory

Abstract BackgroundGastrointestinal (GI) tract graft-vs-host disease (GvHD) is a major cause of post-allo-HCT morbidity and mortality. Patients with steroid-refractory GI-GvHD face a poor prognosis and limited therapeutic options. Here, we report an interim analysis on the safety and efficacy of fecal microbiota transplantation (FMT) in treating steroid-refractory GI-GvHD.MethodsWe did a non-randomized, open-label, phase 1 clinical study on patients with grade IV steroid-refractory GI-GVHD. FMT efficacy was evaluated using indexes of abdominal pain, diarrhea and bloody purulent stool at 14 and 21 days after the diagnosis of steroid-refractory GI-GvHD. The primary outcomes referred to clinical complete remission or partial remission. Secondary outcomes referred to PFS and OS at Day 90 and the end of the research. Safety was evaluated according to adverse events during FMT and the whole follow-up period. The study was registered with ClinicalTrials.gov as #NCT03148743.ResultsA total of 56 patients with steroid-refractory GI-GvHD were enrolled. Of them, 24 patients with grade IV steroid-refractory GI-GvHD were assigned to FMT and 18 to the control group. The characteristics of the two group patients at baseline were similar. At Day 14 after FMT, 13 (54.2%) patients in FMT group and none (0%) of 18 control group achieved clinical remission (p<0.05), while 20(83%) patients in FMT group and 7(39%) in control group showed effective response (clinical remission+partial remission) (RR 7.86, 95% CI 1.88–32.9; p=0.005). At Day 21, the clinical remission was significantly greater in FMT group than in control group (14 (58.3%) of 24 vs 3(16%) of 18; RR 6.0, 95% CI 1.22–29.45; p=0.027). Within a follow up of 90 days, the FMT group showed better OS (HR, 7.0; 95% CI, 1.53-32.08; p=0.012). At the end of the research, the median survival time was >600 days in FMT group and 107 days in control group (HR, 4.73; 95% CI, 1.58-14.14; p=0.005). Both the PFS (HR, 0.24; 95% CI, 0.06-0.95; p=0.055) and OS (HR, 5.97; 95% CI, 1.52-23.43; p=0.01) kept increasing during the follow-up in FMT group. Overall, the mortality rate was lower in FMT group (HR, 5.97; 95% CI, 1.52-23.43; p=0.01). No difference was observed in the occurrence of other side effects, such as hemorrhagic cystitis, infection of bacteria & fungi, CMV&EBV, septicemia, TMA, cardiac events, thrombocytopenia and epilepsy.ConclusionsThe diversity of intestinal microbiota can be affected by allo-HSCT. FMT is effective and safe in treating grade IV steroid refractory GI–GvHD.

scholarly journals 350 The effect of early intervention with fecal microbiota transplantation combined C. butyricum and S. boulardii on weaning stress of piglets

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 94-95
Author(s):  
Quanhang Xiang ◽  
Jian Peng
Keyword(s):  
Early Intervention ◽  
Treatment Group ◽  
Fecal Microbiota Transplantation ◽  
Intestinal Barrier ◽  
Fecal Microbiota ◽  
Intestinal Barrier Function ◽  
Control Group ◽  
Microbiota Composition ◽  
Weaning Stress ◽  
Immunity Function

Abstract This study was designed to determine the effect of early intervention with fecal microbiota transplantation combined C. butyricum and S. boulardii on anti-weaning stress capacity of piglets. 22 pregnant sows were selected in this study, 10 sows were divided into control group (CON), and 12 sows were divided into treatment group (FMT combined C. butyricum and S. boulardii, FMT+C+S). Piglets in CON were gavaged with placebo and piglets in treatment group were gavaged with bacterial solution once daily for the first 3 days after birth. Piglets were weaned at age of 28-day. To explore the effects of early intervention on weaning stress in piglets, after weaning, each group selected 65 healthy piglets to continue feeding for 4 weeks. The growth performance was measured by weekly individual weighing. ADFI during post-weaning period were measured daily. The blood biochemical markers for immunity function, intestinal barrier, and inflammation levels were determined by ELISA kits, and the indices of antioxidant ability were examined using the commercial assay kit. Isolated DNA from fecal were used for 16s rRNA amplicon sequencing to determine microbiota composition. FMT+C+S improved growth rate and decreased diarrhea rate both in sucking and post-weaning period in piglets. FMT+C+S significantly increased immunity function, intestinal barrier function, antioxidant capacity, and reduced inflammation levels in weaned piglets. FMT+C+S significantly increased the abundance of Firmicutes in feces before and after weaning (P &lt; 0.01). In addition, at the genus level, several beneficial bacteria, such as Phascolarctobacterium, Oscillospira, Faecalibacterium, etc. were significantly enriched (P &lt; 0.05) before weaning, and Lactobacillus, Lachnospira, Bacillus, Lysinibacillus, etc. were enriched significantly (P &lt; 0.05) after weaning. These results suggested that early intervention with fecal microbiota transplantation combined C. butyricum and S. boulardii may be a effectively method to promote piglets growth and protect piglets from weaning stress, and even disease, through regulating gut microbiota composition.

scholarly journals Effects of different treatment of faecal microbiota transplantation techniques on ulcerative colitis in rats

2021 ◽  
Author(s):  
Fangyuan Zhu ◽  
Yifan Ke ◽  
Yiting Luo ◽  
Jiaqian Wu ◽  
Pei Wu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Microbiota Transplantation ◽  
Bacterial Flora ◽  
Intestinal Flora ◽  
Clinical Manifestations ◽  
Fecal Microbiota ◽  
Control Group ◽  
Faecal Microbiota ◽  
Faecal Microbiota Transplantation ◽  
Model Control

Abstract Background: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease with abdominal pain, mucus, pus, and blood in the stool as the main clinical manifestations. The pathogenesis of UC is still not completely clear, and multiple factors such as genetic susceptibility, immune response, intestinal microecological changes, and environmental factors together lead to the onset of UC. In recent years, the role of intestinal flora disturbance on the pathogenesis of UC has received widespread attention. Therefore, fecal microbiota transplantation(FMT), which changes the intestinal microecological environment of UC patients by transplantation of normal fecal bacteria, has attracted increasing attention from researchers. However, there are no guidelines at home and abroad to recommend fresh FMT or frozen FMT in the treatment of UC, and there are a few studies on this. Therefore the purpose of this experiment was to explore the effects of fresh and frozen fecal microbiota transplantation methods on the treatment of experimental ulcerative colitis models in rats.Results: Compared with the model control group, all faecal microbiota transplantation groups achieved better efficacy, mainly manifested as weight gain by the rats, improvements in faecal characteristics and blood stools, reduced inflammatory factors, and normal bacterial flora. The efficacy of the frozen faecal microbiota transplantation group was better than that of the fresh faecal microbiota transplantation group in terms of behaviour and colon length .Conclusions: FMT is a feasible method for treating UC. The mechanism of action may be via competitive inhibition of pathogenic microorganisms, improved immune metabolism, and reduced inflammatory response to mitigate the damage to the intestinal barrier and cause UC remission. Compared with fresh FMT, the therapeutic effect of frozen FMT may be greater.

scholarly journals Effect of a High-Fat Diet on the Small-Intestinal Environment and Mucosal Integrity in the Gut-Liver Axis

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3168
Author(s):  
Takashi Nakanishi ◽  
Hirokazu Fukui ◽  
Xuan Wang ◽  
Shin Nishiumi ◽  
Haruka Yokota ◽  
...  
Keyword(s):  
Small Intestine ◽  
Bile Acids ◽  
High Fat Diet ◽  
Small Intestinal Mucosa ◽  
High Fat ◽  
Mucosal Permeability ◽  
Mucosal Integrity ◽  
Junction Molecules ◽  
Intestinal Contents ◽  
Small Intestinal

Although high-fat diet (HFD)-related dysbiosis is involved in the development of steatohepatitis, its pathophysiology especially in the small intestine remains unclear. We comprehensively investigated not only the liver pathology but also the microbiome profile, mucosal integrity and luminal environment in the small intestine of mice with HFD-induced obesity. C57BL/6J mice were fed either a normal diet or an HFD, and their small-intestinal contents were subjected to microbial 16S rDNA analysis. Intestinal mucosal permeability was evaluated by FITC-dextran assay. The levels of bile acids in the small-intestinal contents were measured by liquid chromatography/mass spectrometry. The expression of tight junction molecules, antimicrobial peptides, lipopolysaccharide and macrophage marker F4/80 in the small intestine and/or liver was examined by real-time RT-PCR and immunohistochemistry. The abundance of Lactobacillus was markedly increased and that of Clostridium was drastically decreased in the small intestine of mice fed the HFD. The level of conjugated taurocholic acid was significantly increased and those of deconjugated cholic acid/secondary bile acids were conversely decreased in the small-intestinal contents. The expression of occludin, antimicrobial Reg IIIβ/γ and IL-22 was significantly decreased in the small intestine of HFD-fed mice, and the intestinal permeability was significantly accelerated. Infiltration of lipopolysaccharide was significantly increased in not only the small-intestinal mucosa but also the liver of HFD-fed mice, and fat drops were apparently accumulated in the liver. Pathophysiological alteration of the luminal environment in the small intestine resulting from a HFD is closely associated with minimal inflammation involving the gut-liver axis through disturbance of small-intestinal mucosal integrity.

scholarly journals Small intestinal flora graft alters fecal flora, stool, cytokines and mood status in healthy mice

2021 ◽  
Vol 4 (9) ◽  
pp. e202101039
Author(s):  
Yinyin Xie ◽  
Linyang Song ◽  
Junhua Yang ◽  
Taoqi Tao ◽  
Jing Yu ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Healthy Adult ◽  
Fecal Microbiota Transplantation ◽  
Intestinal Flora ◽  
Fecal Microbiota ◽  
Microbial Composition ◽  
Healthy Adult Male ◽  
Wet Weight ◽  
Small Intestinal ◽  
Slight Alteration

Fecal microbiota transplantation is widely used. Large intestinal microbiota (LIM) is more similar to fecal microbiota than small intestinal microbiota (SIM). The SIM communities are very different from those of LIM. Therefore, SIM transplantation (SIMT) and LIM transplantation (LIMT) might exert different influences. Here, healthy adult male C57Bl/6 mice received intragastric SIMT, LIMT, or sterile PBS administration. Microbiota graft samples were collected from small/large intestine of healthy mice of the same age, sex, and strain background. Compared with PBS treatment, SIMT increased pellet number, stool wet weight, and stool water percentage; induced a fecal microbiota profile shift toward the microbial composition of the SIM graft; induced a systemic anti-inflammatory cytokines profile; and ameliorated depressive-like behaviors in recipients. LIMT, however, induced merely a slight alteration in fecal microbial composition and no significant influence on the other aspects. In sum, SIMT, rather than LIMT, affected defecation features, fecal microbial composition, cytokines profile, and depressive-like behaviors in healthy mice. This study reveals the different effects of SIMT and LIMT, providing an interesting clue for further researches involving gut microbial composition change.

scholarly journals Fecal microbiota transplantation mitigates bone loss by improving gut microbiome composition and gut barrier function in aged rats

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12293
Author(s):  
Sicong Ma ◽  
Ning Wang ◽  
Pu Zhang ◽  
Wen Wu ◽  
Lingjie Fu
Keyword(s):  
Bone Loss ◽  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Bone Volume ◽  
Female Rats ◽  
Control Group ◽  
Aged Rats ◽  
Senile Osteoporosis ◽  
Microbiome Composition

Background Gut microbiota (GM) dysbiosis is closely related to bone loss and the occurrence of osteoporosis in animals and human. However, little is known about the effect and the mechanisms of fecal microbiota transplantation (FMT) on bone in the treatment of senile osteoporosis. Methods Aged female rats were randomly divided into the FMT group and the control group. 3-month-old female rats were used as fecal donors. The rats were sacrificed at 12 and 24 weeks following transplantation and the serum, intestine, bone, and feces were collected for subsequent analyses. Results The bone turnover markers of osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), and carboxy-terminal peptide (CTX) decreased significantly at 12 and 24 weeks following FMT (P < 0.05). At 12 weeks following transplantation, histomorphometric parameters including the bone volume (BV), trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) of the FMT group were comparable to the control group. However, at 24 weeks following transplantation, these parameters of the FMT group were significantly higher than those of the control group (P < 0.05). Besides, the GM aggregated at 12 and 24 weeks following FMT, and the ecological distance was close between the rats in the FMT group and the donor rats. Alpha diversity, shown by the Shannon index and Simpson index, and the Firmicutes/Bacteroidetes ratio decreased significantly after FMT at 24 weeks. Furthermore, FMT restored the GM composition in aged rats at the phylum and family level, and the intestinal microbiota of the aged rats was similar to that of the donor rats. Correlation network analysis indirectly suggested the causality of FMT on alleviating osteoporosis. FMT improved the intestinal structure and up-regulated the expression of tight junction proteins of occludin, claudin, and ZO-1, which might be associated with the protective effects of FMT on bone. Conclusions GM transplanted from young rats alleviated bone loss in aged rats with senile osteoporosis by improving gut microbiome composition and intestinal barrier function. These data might provide a scientific basis for future clinical treatment of osteoporosis through FMT.

Fecal Microbiota Transplantation Repairs Intestinal Mucosal Barrier Injury in Mice with Ulcerative Colitis

2021 ◽  
Vol 15 (5) ◽  
pp. 679-684
Author(s):  
Yijuan Lin ◽  
Jian Ding ◽  
Xunru Huang ◽  
Jintong Chen ◽  
Chengdang Wang
Keyword(s):  
Structural Changes ◽  
Fecal Microbiota Transplantation ◽  
Intestinal Barrier ◽  
Fecal Microbiota ◽  
Mucosal Barrier ◽  
Control Group ◽  
Model Group ◽  
Intestinal Mucosal Barrier ◽  
Mucosal Barrier Injury ◽  
Group A

This study aimed to explore the effects of fecal microbiota transplantation (FMT) on intestinal mucosal barrier injury in mice with ulcerative colitis (UC) and to elucidate the underlying mechanisms. Dextran sodium sulfate (DSS) was administered to develop the UC mouse model. Next, the experiment was divided into a normal control group, a DSS model group, a DSS+5-amino acid salicylic acid (5-ASA) group, and a DSS+FMT group. Hematoxylin–eosin staining was used to detect pathological changes; transmission electron microscopy was used to evaluate structural changes of intestinal mucosa; enzyme-linked immunosorbent assay (ELSIA) was used to detect endotoxins; and western blotting was used to detect the expression of zonula occludens-1 (ZO-1). In the control group, the intestinal mucosa and microvilli were intact, epithelial cells were closely connected, and the intercellular space was narrow. By contrast, focal intestinal barrier defects, including shallow ulcer, local inflammatory cell infiltration, hyperplasia of connective tissue, and loss of gland structure were observed in the model group. These abnormal morphological and structural changes were ameliorated by 5-ASA and FMT. Compared with the control group, the endotoxin content increased significantly, and the ZO-1 protein expression decreased significantly in the model group (P < 0.05). By contrast, the endotoxin level decreased significantly, and the ZO-1 protein expression increased significantly in the 5-ASA group and FMT group compared with that of the model group (P < 0.05). FMT ameliorates UC by repairing the intestinal barrier function, which is likely involved in upregulating ZO-1 expression.

Fecal microbiota transplantation for TKI-induced diarrhea in patients with metastatic renal cell carcinoma.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 615-615 ◽  
Author(s):  
Ernesto Rossi ◽  
Gianluca Ianiro ◽  
Brigida Anna Maiorano ◽  
Roberto Iacovelli ◽  
Loris Lopetuso ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Dose Reduction ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Fecal Microbiota Transplantation ◽  
Controlled Trial ◽  
Fecal Microbiota ◽  
Control Group ◽  
Serious Adverse Events

615 Background: Diarrhea is a common adverse event of tyrosine kinase inhibitors (TKI). No standard treatment for TKI-induced diarrhea has been established, although probiotics are commonly used. In several patients TKI dose reduction is necessary. Data showing the interplay between microbiota and TKI-induced diarrhea are reported. The therapeutic modulation of gut microbiota could be useful to ameliorate TKI-related diarrhea. Our study aims to explore the efficacy and safety of fecal microbiota transplantation (FMT), compared with current clinical practice approach, for the treatment of TKI-associated diarrhea in patients with metastatic renal cell carcinoma. Methods: Patients on treatment with Pazopanib/Sunitinib as first line therapy for metastatic renal cell carcinoma and TKI-associated diarrhea (³ 4 stools per day over baseline) were randomize to receive FMT from healthy donor by colonoscopy (fresh faeces) or probiotics (L. casei DG). The primary endpoint was the resolution of TKI-related diarrhea. Baseline fecal samples were collected from all patients and donors. All patients were followed up 7, 15, 30 and 60 days after the treatment for diarrhea. Results: 21 subjects, 10 in FMT arm and 11 in control arm, have been enrolled. At 7 day-follow-up, TKI-related diarrhea disappeared in 10 patients of the FMT group and in 6 patients of the control group (100% vs 54.5%, p = 0.02). At 15-day and 30-day, 9 patients in the FMT group and 0 patients in the control group experienced resolution of diarrhea (90% vs 0%, p = 0.0001). At 60-days 8/10 patients in FMT arm did not have diarrhea. Dose reduction was necessary in 4 patients of the control group. No serious adverse events associated with any of the two treatment protocols were observed. Metagenomic analyses on collected stool samples are ongoing. Conclusions: This open-label randomised controlled trial showed the effectiveness and safety of FMT compared with probiotics in curing TKI-related diarrhea in patients with metastatic renal cell carcinoma, avoiding the necessity of dose reduction. Considering the increasing evidence, the modulation of microbiota trough FMT could also affect the efficacy of immunotherapy for metastatic renal cell carcinoma.

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