Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation

Shen, Zhaohua; Zhu, Changxin; Quan, Yongsheng; Yang, Zhenyu; Wu, Shuai; Luo, Weiwei; Tan, Bei; Wang, Xiaoyan

doi:10.3748/wjg.v24.i1.5

Cited by 485 publications

(366 citation statements)

References 93 publications

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“…We found through functional prediction that the relative abundance of intestinal flora was significantly different in infectious diseases. Further analysis of the species composition of the different pathways revealed that Lachnospiraceae contributed the most to L-lysine fermentation to acetate and butanoate, consistent with previous studies 50 . This indicated that Lachnospiraceae may be the key bacteria for the effectiveness of FMT.…”

Section: Analysis Of Short-chain Fatty Acids (Scfas) By Lc-mssupporting

confidence: 89%

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

Gai

Wang

et al. 2020

Preprint

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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 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.

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Section: Analysis Of Short-chain Fatty Acids (Scfas) By Lc-mssupporting

confidence: 89%

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

Gai

Wang

et al. 2020

Preprint

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“…The gut microbiota is involved in the development of intestinal inflammation and UC. Therefore, microbial manipulation could be an alternative therapeutic approach for UC (47). FMT may serve as an effective treatment strategy for UC, as it is able to correct the altered gut microbial community and restore microbial homeostasis (48).…”

Section: Discussionmentioning

confidence: 99%

Fecal microbiota transplantation ameliorates active ulcerative colitis

Chen

Huang

et al. 2020

Exp Ther Med

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Ulcerative colitis (UC) is a complex chronic pathological condition of the gut in which microbiota targeted treatment, such as fecal microbiota transplantation (FMT), has shown an encouraging effect. The aim of the present study was to investigate the efficacy and safety of FMT in patients with mild or moderate UC. A single-center, open-label study was designed, including 47 patients with mild or moderate active UC who received three treatments of fresh FMT via colonic transendoscopic enteral tubing within 1 week. The inflammatory bowel disease questionnaire, partial Mayo scores, colonoscopy, erythrocyte sedimentation rate, C-reactive protein level and procalcitoin values were used to assess the efficacy of FMT and alteration in gut microbiota was detected by 16S ribosomal RNA-sequencing. Before FMT, microbiota Faecalibacterium prausnitzii (F. prausnitzii) levels were significantly decreased in patients with UC compared with healthy donors (P<0.01). At 4 weeks post-FMT, F. prausnitzii levels were significantly increased (P<0.05), and the Mayo score was significantly decreased (1.91±1.07 at baseline vs. 4.02±1.47 at week 4; P<0.001) in patients with UC compared with healthy donors. Steroid-free clinical responses were reported in 37 patients (84.1%), and steroid-free clinical remission was achieved in 31 patients (70.5%) at week 4 post-FMT, however, steroid-free remission was not achieved in any patient. No adverse events were reported in 41 (93.2%) patients after FMT or during the 12-week follow-up. Shannon's diversity index and Chao1 estimator were also improved in patients with UC receiving FMT. In conclusion, the results of the present study suggested that FMT resulted in clinical remission in patients with mild to moderate UC, and that the remission may be associated with significant alterations to the intestinal microbiota of patients with UC. Furthermore, F. prausnitzii may serve as a diagnostic and therapeutic biomarker for the use of FMT in UC.

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“…Cell shedding represents an important host physiological response which ensures continuity of the intestinal epithelial layer despite continuous replacement of intestinal epithelial cells every 3-5 days [11]. Crucially, intestinal inflammation is correlated with elevated or 'pathological' cell shedding, which is also correlated with altered microbiota profiles [12][13][14]. Previous studies have indicated that antibiotic usage, and antibiotic-induced microbiota perturbations, particularly in infancy, are linked to increased risk of developing inflammatory disorders in later life [15].…”

Section: Introductionmentioning

confidence: 99%

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

Hughes

Schofield

Dalby

et al. 2019

Preprint

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AbstractThe gut microbiota plays a crucial role in regulating and maintaining the epithelial barrier, particularly during early life. Notably, patients with chronic intestinal inflammation have a dysregulated process of renewal and replenishment of the intestinal epithelial cell (IEC) barrier, which is linked to disturbances in the gut microbiota. To date, there are no studies focussed on understanding the impact of inflammatory cell shedding events during the early life developmental window, and which host and microbial factors mediate these responses. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period (day 14, 21, 29 and week 8). Surprisingly neonatal mice (day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of LPS, with day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses, although we did observe that neonatal mice had elevated anti-inflammatory (IL-10) responses. Notably, when we profiled microbiota and metabolites from these mice, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Faecal microbiota transplant (FMT) and antibiotic studies confirmed the importance of early life gut microbiota in cell shedding responses. In these studies, neonates treated with antibiotics restored LPS-induced small intestinal cell shedding, whereas adult FMT alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlight areas for further investigation to probe underlying mechanisms to drive therapeutic development within the context of chronic inflammatory intestinal diseases.

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Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation

Cited by 485 publications

References 93 publications

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

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

Fecal microbiota transplantation ameliorates active ulcerative colitis

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

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