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

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.

Download Full-text

Effects of Different Treatment of Fecal Microbiota Transplantation Techniques on Treatment of Ulcerative Colitis in Rats

Frontiers in Microbiology ◽

10.3389/fmicb.2021.683234 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fangyuan Zhu ◽

Yifan Ke ◽

Yiting Luo ◽

Jiaqian Wu ◽

Pei Wu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Fecal Microbiota Transplantation ◽

Clinical Manifestations ◽

Intestinal Barrier ◽

Fecal Microbiota ◽

Mucosal Barrier ◽

Inflammatory Factors ◽

Control Group ◽

Model Control ◽

Acid Producing Bacteria

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 microbiota disturbances 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 to recommend fresh FMT or frozen FMT in the treatment of UC, and there are few studies on this. Therefore, the purpose of this study was to explore the effects of fresh and frozen FMT methods on the treatment of experimental UC models in rats.Results: Compared with the model control group, all FMT groups achieved better efficacy, mainly manifested as weight gain by the rats, improvements in fecal characteristics and blood stools, reduced inflammatory factors and normal bacterial microbiota. The efficacy of the frozen FMT group was better than that of the fresh FMT group in terms of behavior and colon length.Conclusion: FMT method supplements the gut microbiota with beneficial bacteria, such as short-chain fatty acid-producing bacteria. These bacteria can regulate intestinal function, protect the mucosal barrier and reduce harmful bacteria, thus mitigating the damage to the intestinal barrier and the associated inflammatory response, resulting in UC remission. FMT is a feasible method for treating UC, with frozen FMT having a superior therapeutic effect than that of fresh FMT.

Download Full-text

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

Journal of Animal Science ◽

10.1093/jas/skz258.195 ◽

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 < 0.01). In addition, at the genus level, several beneficial bacteria, such as Phascolarctobacterium, Oscillospira, Faecalibacterium, etc. were significantly enriched (P < 0.05) before weaning, and Lactobacillus, Lachnospira, Bacillus, Lysinibacillus, etc. were enriched significantly (P < 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.

Download Full-text

Fecal microbiota transplantation reconstructs the gut microbiota of septic mice and protects the intestinal mucosal barrier

10.1101/2020.06.22.164541 ◽

2020 ◽

Author(s):

Xiaowei Gai ◽

Huawei Wang ◽

Yaqing Li ◽

Haotian Zhao ◽

Cong He ◽

...

Keyword(s):

Fatty Acid ◽

Gut Microbiota ◽

Tight Junction ◽

Short Chain Fatty Acid ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Chain Fatty Acid ◽

Mucosal Barrier ◽

Mucus Layer ◽

Intestinal Mucosal Barrier

AbstractThe gastrointestinal (GI) tract has long been hypothesized to play an integral role in the pathophysiology of sepsis, and gut microbiota (GM) dysbiosis may be the key factor. Previous studies has confirmed that microbiome is markedly altered in critical illness. We aimed to confirm the existence of gut microbiota imbalance in the early stage of sepsis, observe the effect of fecal microbiota transplantation (FMT) on sepsis, and explore whether FMT can reconstruct the GM of septic mice and restore its protective function on the intestinal mucosal barrier. Through the study of flora, mucus layer, tight junction, immune barrier, and short-chain fatty acid changes in septic mice and fecal microbiota transplanted mice, we found that GM imbalance exists early in sepsis. FMT can improve morbidity and effectively reduce mortality in septic mice. After the fecal bacteria were transplanted, the abundance and diversity of the gut flora were restored, and the microbial characteristics of the donors changed. FMT can effectively reduce epithelial cell apoptosis, improve the composition of the mucus layer, upregulate the expression of tight junction proteins, and reduce intestinal permeability and the inflammatory response, thus protecting the intestinal barrier function. After FMT, Lachnospiraceae contributes the most to intestinal protection through enhancement of the L-lysine fermentation pathway, resulting in the production of acetate and butanoate, and may be the key bacteria for short-chain fatty acid metabolism and FMT success.

Download Full-text

Fecal microbiota transplantation reconstructs the gut microbiota of septic mice and protects the intestinal mucosal barrier

10.21203/rs.3.rs-52217/v1 ◽

2020 ◽

Author(s):

Xiaowei Gai ◽

Huawei Wang ◽

Yaqing Li ◽

Haotian Zhao ◽

Cong He ◽

...

Keyword(s):

Gut Microbiota ◽

Sham Group ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Mucosal Barrier ◽

Intragastric Administration ◽

Mucus Layer ◽

Gut Flora ◽

Protective Function ◽

Intestinal Mucosal Barrier

Abstract Background This study aimed to confirm the existence of gut microbiota (GM) imbalance in the early stage of sepsis, observe the effect of fecal microbiota transplantation (FMT) on sepsis, and explore whether FMT can reconstruct the GM of septic mice and restore its protective function on the intestinal mucosal barrier. Methods The study included acute experiments and 7-day mortality observation experiments with clean-grade C57BL/6, and they were randomly divided randomly into three groups, namely, the sham group, the sepsis model group and the fecal microbiota transplantation group. Fresh feces from 10 mice were kept every day to make fecal liquid. The Sham group and the CLP group were given intragastric administration once a day with phosphate-buffered saline, and the FMT group mice were given fecal microbiota transplantation once a day. The animals were euthanized at 12, 24, and 48 h after modeling, and blood, colon, and stool from each mouse were collected at the same time.Results Colonic pathological scores, pro-inflammatory cytokines, TLR4/MyD88/NF-κB protein levels, and gene expression levels, were lower in the FMT group, while anti-inflammatory factors, mucus layer thickness, MUC2, occludin, and ZO-1 proteins were higher in the FMT group than the CLP group. Bacterial flora analysis showed gut flora was reconstructed after FMT. The species composition of the differential pathways revealed that the Lachnospiraceae group contributed the most by the L-lysine pathway of fermentation to acetate and butanoate.Conclusion GM imbalance exists early in sepsis. FMT can improve morbidity and effectively reduce mortality in septic mice. After the fecal bacteria were transplanted, the abundance and diversity of the gut flora were restored, and the microbial characteristics of the donors changed. FMT can effectively reduce epithelial cell apoptosis, improve the composition of the mucus layer, upregulate the expression of tight junction proteins, and reduce intestinal permeability and the inflammatory response, thus protecting the intestinal barrier function. After FMT, Lachnospiraceae contributes the most to intestinal protection through enhancement of the L-lysine fermentation pathway, resulting in the production of acetate and butanoate, and may be the key bacteria for short-chain fatty acid metabolism and FMT success.

Download Full-text

The Effect of Peritoneal Air Exposure on Intestinal Mucosal Barrier

Gastroenterology Research and Practice ◽

10.1155/2014/674875 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 9

Author(s):

Jun Bao ◽

Shanjun Tan ◽

Wenkui Yu ◽

Zhiliang Lin ◽

Yi Dong ◽

...

Keyword(s):

Terminal Ileum ◽

Inflammatory Cells ◽

Mucosal Injury ◽

Mucosal Barrier ◽

Control Group ◽

Sprague Dawley ◽

Air Exposure ◽

Intestinal Mucosal Barrier ◽

Group A ◽

Lactate Levels

Background. Damage of the intestinal mucosa barrier may result in intestinal bacterial and endotoxin translocation, leading to local and systemic inflammation. The present study was designed to investigate whether peritoneal air exposure induces damage of intestinal mucosal barrier.Methods. Sprague-Dawley rats (weighing 210 to 230 g) were randomized into five groups (6/group): a control group, a sham group, and three exposure groups with peritoneal air exposure for 1, 2, and 3 h, respectively. At 24 h after surgery, blood and terminal ileum were sampled. The serum D-lactate levels were determined using an ELISA kit. The intestinal permeability was determined by measuring the intestinal clearance of FITC-dextran (FD4). The histopathological changes in terminal ileum were also assessed.Results. Compared with the controls, peritoneal air exposure caused an increase in both serum D-lactate level and intestinal FD4 clearance, which were proportional to the length of peritoneal air exposure and correlated to Chiu’s scores, indices for intestinal mucosal injury. Edema and inflammatory cells were also observed in mucosa and submucosa of ileum in three exposure groups.Conclusions. Peritoneal air exposure could induce damage to the intestinal mucosal barrier, which is proportional to the time length of peritoneal air exposure.

Download Full-text

Fecal Microbiota Transplantation Protects the Intestinal Mucosal Barrier by Reconstructing the Gut Microbiota in a Murine Model of Sepsis

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.736204 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiaowei Gai ◽

Huawei Wang ◽

Yaqing Li ◽

Haotian Zhao ◽

Cong He ◽

...

Keyword(s):

Inflammatory Response ◽

Gut Microbiota ◽

Murine Model ◽

Barrier Function ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Mucosal Barrier ◽

Gut Flora ◽

Intestinal Mucosal Barrier ◽

Mucosal Barrier Function

The gastrointestinal (GI) tract has long been hypothesized to play an integral role in the pathophysiology of sepsis, and gut microbiota (GM) dysbiosis may be the key factor. Previous studies have shown that the gut flora was significantly altered in critically ill patients. This study aimed to observe what kind of GM dysbiosis is in the early stage of sepsis and whether the application of fecal microbiota transplantation (FMT) can reconstruct the GM of septic mice and restore its protective function on the intestinal mucosal barrier. The study investigated the effect of FMT on gut microbiota, mucosal barrier function, inflammatory response, and survival in a murine model of sepsis established by cecal ligation and puncture (CLP). It is found that FMT can not only reduce morbidity and mortality and restore the abundance and diversity of the gut flora in septic mice, but can also improve the intestinal barrier function by reducing epithelial cell apoptosis, improving the composition of the mucus layer, upregulating the expression of tight junction proteins, and reducing intestinal permeability and the inflammatory response. After FMT, Lachnospiraceae contributed the most to intestinal protection through enhancement of the L-lysine fermentation pathway. FMT offers a microbe-mediated survival advantage in a murine model of sepsis. Therefore, an improved understanding of the connection between microbiota, and systemic illness may yield new therapeutic strategies for patients with sepsis.

Download Full-text

Anterior Gradient Protein 2 Promotes Mucosal Repair in Pediatric Ulcerative Colitis

BioMed Research International ◽

10.1155/2021/6483860 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Xiaolin Ye ◽

Jie Wu ◽

Jing Li ◽

Hongyu Wang

Keyword(s):

Ulcerative Colitis ◽

Mucosal Injury ◽

Mucosal Healing ◽

Mucosal Barrier ◽

Control Group ◽

Intestinal Epithelial ◽

Intestinal Mucosal Barrier ◽

Mucosal Barrier Injury ◽

Tnf Α

Mucosal healing comprises a key goal of ulcerative colitis (UC) treatment. Anterior gradient protein 2 (AGR2) plays an important role in maintaining intestinal homeostasis in UC. However, the role of AGR2 in the repair of mucosal injury is not yet clear. This study is aimed at investigating the expression of AGR2 in the intestinal tissues of children with UC and its role in repairing mucosal injury. Forty UC patients who were hospitalized in the Pediatric Gastroenterology Ward of Shengjing Hospital affiliated with China Medical University between July 1, 2013, and May 31, 2020, and 20 children who had normal colonoscopy results during the same period (control group) made up the study sample. The disease activity of UC was evaluated based on the pediatric ulcerative colitis activity index, and the ulcerative colitis endoscopic index was evaluated according to the Rachmilewitz score. Immunohistochemical staining was employed to examine the differences in AGR2 expression in the intestinal mucosa between groups. The protective effect of AGR2 in a model of tumor necrosis factor-alpha- (TNF-α-) induced intestinal mucosal barrier injury and the underlying molecular mechanism were explored through in vitro experiments. The results showed that compared with the normal control group, UC patients in the remission or active period had significantly higher expression of AGR2 in the intestine. AGR2 expression was positively correlated with Ki67, an intestinal epithelial cell proliferation marker, but negatively correlated with the degree of endoscopic mucosal injury. In an in vitro model, AGR2 overexpression promoted cell proliferation and migration and inhibited TNF-α-induced intestinal epithelial barrier damage by activating yes-associated protein (YAP). Collectively, our study suggests that AGR2 might serve as a valuable biomarker to help assess the condition and mucosal healing status of UC patients. In vitro, AGR2 promoted the repair of intestinal mucosal barrier injury by activating YAP.

Download Full-text

Maternal Emulsifier P80 Intake Induces Gut Dysbiosis in Offspring and Increases Their Susceptibility to Colitis in Adulthood

mSystems ◽

10.1128/msystems.01337-20 ◽

2021 ◽

Vol 6 (2) ◽

Author(s):

Ge Jin ◽

Qiang Tang ◽

Jiaheng Ma ◽

Xiang Liu ◽

Bingqian Zhou ◽

...

Keyword(s):

Intestinal Inflammation ◽

Fecal Microbiota Transplantation ◽

Intestinal Barrier ◽

Pharmaceutical Formulations ◽

Structural Disorder ◽

Fecal Microbiota ◽

Control Group ◽

Low Grade ◽

Gut Dysbiosis ◽

Early Life Events

ABSTRACT Early life events can lead to multiple diseases in adulthood. Previous studies suggested that polysorbate 80 (P80) as a widely used emulsifier in pharmaceutical formulations and food industries could impair the intestinal barrier. However, whether maternal P80 (MP80) exposure could affect the long-term health of offspring remains unknown. In this study, we found that maternal P80 intake could retard intestinal development, disrupt the intestinal barrier, and cause low-grade intestinal inflammation in 3-week-old offspring. 16S rRNA sequencing and correlation analysis revealed that Mucispirillum, Clostridium XI, and Parabacteroides, which positively correlated with intestinal proliferation and differentiation, were decreased in the maternal P80 group. Interestingly, the increase in some harmful bacteria, including Proteobacteria, Helicobacteraceae, Campylobacterales, and Desulfovibrionales, persisted from the weaning period to adulthood (3 to 8 weeks). Furthermore, a fecal microbiota transplantation assay showed that the mice gavaged with feces from 3-week-old offspring of the MP80 group presented more severe intestinal inflammation and barrier disruption than the mice that received feces from the offspring of the control group. Finally, maternal P80 intake remarkably aggravated the structural disorder of intestinal crypt, increased proinflammatory factors, and exacerbated dextran sulfate sodium (DSS)-induced colitis in adulthood. Conclusively, maternal P80 intake could induce gut dysbiosis and promote colitis susceptibility in adulthood. This study provides new insights into the prevention of inflammatory bowel disease (IBD). IMPORTANCE The main findings of this research showed that maternal P80 intake could disrupt the intestinal barrier, induce gut dysbiosis, and promote colitis susceptibility in adulthood. This study will enhance understanding of the prevention of IBD.

Download Full-text

Microecological preparation combined with an modified low-carbon diet improves glucolipid metabolism and cardiovascular complication in obese patients

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00697-6 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Jianguo Liu ◽

Liehui Xiao ◽

Hezhongrong Nie ◽

Yong Pan ◽

Yan Liu ◽

...

Keyword(s):

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Control Group ◽

Obese Patients ◽

Carotid Atherosclerotic Plaque ◽

Low Carbon ◽

Balanced Diet ◽

Group A ◽

Group B ◽

Control Group Group

Abstract Objective To investigate the impact of microecological preparation combined with modified low-carbon diet on the glucolipid metabolism and cardiovascular complication in obese patients. Methods From August 2017 to July 2020, 66 obese patients were recruited, and administrated with an modified low-carbon diet with (group A) or without (Group B) microecology preparation and a balanced diet in control group (group C) for 6 months. Meanwhile, 20 volunteers administrated with a balanced diet were recruited as the healthy control group (group D). Results After 6-month intervention, obese subjects in group A and B showed significant improvement of body and liver fat mass, reduction of serum lipid levels, intestinal barrier function markers, insulin resistance index (IRI), high blood pressure (HBP) and carotid intima thickness, as compared with subjects in group C. More importantly, subjects in group A had better improvement of vascular endothelial elasticity and intimal thickness than subjects in group B. However, these intervention had no effect on carotid atherosclerotic plaque. Conclusion Administration of microecological preparation combined with modified low-carbon diet had better improvement of intestinal barrier function, glucose and lipid metabolism, and cardiovascular complications than low-carbon diet in obese patients, but the effect of a simple low-carb diet on carotid atherosclerotic plaque need to be further addressed.

Download Full-text

Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis

Biomedicines ◽

10.3390/biomedicines9020145 ◽

2021 ◽

Vol 9 (2) ◽

pp. 145

Author(s):

Julio Plaza-Díaz ◽

Patricio Solis-Urra ◽

Jerónimo Aragón-Vela ◽

Fernando Rodríguez-Rodríguez ◽

Jorge Olivares-Arancibia ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Liver Steatosis ◽

Intestinal Barrier ◽

Fecal Microbiota ◽

Current Treatment ◽

Immune Defense ◽

Alcoholic Fatty Liver ◽

The Impact

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).

Download Full-text