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 ◽  
...  

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.

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Francesco Strati ◽  
Meritxell Pujolassos ◽  
Claudia Burrello ◽  
Maria Rita Giuffrè ◽  
Georgia Lattanzi ◽  
...  

Abstract Background The gut microbiota plays a central role in host physiology and in several pathological mechanisms in humans. Antibiotics compromise the composition and functions of the gut microbiota inducing long-lasting detrimental effects on the host. Recent studies suggest that the efficacy of different clinical therapies depends on the action of the gut microbiota. Here, we investigated how different antibiotic treatments affect the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in an experimental colitis model and in ex vivo experiments with human intestinal biopsies. Results Murine fecal donors were pre-treated with different antibiotics, i.e., vancomycin, streptomycin, and metronidazole before FMT administration to colitic animals. The analysis of the gut microbiome, fecal metabolome, and the immunophenotyping of colonic lamina propria immune cells revealed that antibiotic pre-treatment significantly influences the capability of the microbiota to control intestinal inflammation. Streptomycin and vancomycin-treated microbiota failed to control intestinal inflammation and were characterized by the blooming of pathobionts previously associated with IBD as well as with metabolites related to the presence of oxidative stress and metabolism of simple sugars. On the contrary, the metronidazole-treated microbiota retained its ability to control inflammation co-occurring with the enrichment of Lactobacillus and of innate immune responses involving iNKT cells. Furthermore, ex vivo cultures of human intestinal lamina propria mononuclear cells and iNKT cell clones from IBD patients with vancomycin pre-treated sterile fecal water showed a Th1/Th17 skewing in CD4+ T-cell populations; metronidazole, on the other hand, induced the polarization of iNKT cells toward the production of IL10. Conclusions Diverse antibiotic regimens affect the ability of the gut microbiota to control intestinal inflammation in experimental colitis by altering the microbial community structure and microbiota-derived metabolites.


2020 ◽  
Vol 587 ◽  
pp. 119648 ◽  
Author(s):  
Jonas Ghyselinck ◽  
Lynn Verstrepen ◽  
Frédéric Moens ◽  
Pieter Van den Abbeele ◽  
Jawal Said ◽  
...  

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 748 ◽  
Author(s):  
Jin-Young Lee ◽  
Mohamed Mannaa ◽  
Yunkyung Kim ◽  
Jehun Kim ◽  
Geun-Tae Kim ◽  
...  

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.


2020 ◽  
Author(s):  
Dandan Jiang ◽  
Xin He ◽  
Marc Valitutto ◽  
Li Chen ◽  
Qin Xu ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hao-Ming Xu ◽  
Hong-Li Huang ◽  
Jing Xu ◽  
Jie He ◽  
Chong Zhao ◽  
...  

Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography–mass spectrometry (LC–MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested in vitro. The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with Clostridium butyricum-containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.


2021 ◽  
Vol 12 ◽  
Author(s):  
Haoran Ke ◽  
Fang Li ◽  
Wenlin Deng ◽  
Zitong Li ◽  
Siqi Wang ◽  
...  

The present study aimed to determine if metformin exerts anti-inflammatory and mucus-protective effects via the gut microbiota. Metformin has extensive benefits including anti-inflammatory effects. Previous studies showed that metformin changed the gut microbiota composition and increases the number of goblet cells. Intestinal dysbiosis and goblet cell depletion are important features of ulcerative colitis (UC). The underlying mechanism and whether metformin can improve the mucus barrier in UC remain unclear. Metformin (400 mg/kg/day) was administered to mice with dextran sulfate sodium (DSS)-induced UC for 2 wk to investigate the effects of metformin on the intestinal mucus barrier. The gut microbiota was depleted, using antibiotics, to explore its role in the mucus-protecting effects of metformin. Akkermansia muciniphila (A. muciniphila), which was enriched in metformin-treated mice, was administered to mice to investigate the effects of the bacteria on UC and the mucus barrier. Metformin attenuated DSS-induced UC in mice, as evidenced by the alleviation of diarrhea, hematochezia, and the decrease in body weight. The expression of mucin2, a prominent mucus barrier protein, was increased in the metformin-treated group compared to the DSS-treated group. Furthermore, fecal 16S rRNA analysis showed that metformin treatment changed the gut microbiota composition by increasing the relative abundance of Lactobacillus and Akkermansia species while decreasing Erysipelatoclostridium at the genus level. Antibiotic treatment partly abolished the anti-inflammatory and mucus-protecting effects of metformin. Administration of A. muciniphila alleviated the colonic inflammation and mucus barrier disruption. Metformin alleviated DSS-induced UC in mice and protected against cell damage via affecting the gut microbiota, thereby providing a new mechanism for the therapeutic effect of metformin in patients with UC. This study also provides evidence that A. muciniphila as a probiotic has potential benefits for UC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Rongrong Ren ◽  
Xuefeng Gao ◽  
Yichao Shi ◽  
Jianfeng Li ◽  
Lihua Peng ◽  
...  

Aims: To assess the long-term efficacy and safety of single-donor, low-intensity fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), and to identify the outcome-specific gut bacteria.Design: Thirty-one patients with active UC (Mayo scores ≥ 3) were recruited, and all received FMT twice, at the start of the study and 2∼3 months later, respectively, with a single donor and a long-term follow-up. The fecal microbiome profile was accessed via 16S rRNA sequencing before and after FMT.Results: After the first FMT, 22.58% (7/31) of patients achieved clinical remission and endoscopy remission, with the clinical response rate of 67.74% (21/31), which increased to 55% (11/20) and 80% (16/20), respectively, after the second FMT. No serious adverse events occurred in all patients. During 4 years of follow-up, the mean remission period of patients was 26.5 ± 19.98 m; the relapse rate in the 12 remission patients was 33.33% within 1 year, and 58.3% within 4 years. At baseline, UC patients showed an enrichment in some proinflammatory microorganisms compared to the donor, such as Bacteroides fragilis, Clostridium difficile, and Ruminococcus gnavus, and showed reduced amounts of short-chain fatty acid (SCFA) producing bacteria especially Faecalibacterium prausnitzii. FMT induced taxonomic compositional changes in the recipient gut microbiota, resulting in a donor-like state. Given this specific donor, UC recipients with different outcomes showed distinct gut microbial features before and after FMT. In prior to FMT, relapse was characterized by higher abundances of Bacteroides fragilis and Lachnospiraceae incertae sedis, together with lower abundances of Bacteroides massiliensis, Roseburia, and Ruminococcus; Prevotella copri was more abundant in the non-responders (NR); and the patients with sustained remission (SR) had a higher abundance of Bifidobacterium breve. After FMT, the NR patients had a lower level of Bifidobacterium compared to those with relapse (Rel) and SR, while a higher level of Bacteroides spp. was observed in the Rel group.Conclusion: Low-intensity single donor FMT could induce long remission in active UC. The gut microbiota composition in UC patients at baseline may be predictive of therapeutic response to FMT.


2019 ◽  
Vol 180 (3) ◽  
pp. 165-176 ◽  
Author(s):  
Hanieh-Sadat Ejtahed ◽  
Raul Y Tito ◽  
Seyed-Davar Siadat ◽  
Shirin Hasani-Ranjbar ◽  
Zahra Hoseini-Tavassol ◽  
...  

Objective The increasing prevalence of obesity over the past few decades constitutes a global health challenge. Pharmacological therapy is recommended to accompany life-style modification for obesity management. Here, we perform a clinical trial to investigate the effects of metformin on anthropometric indices and gut microbiota composition in non-diabetic, treatment-naive obese women with a low-calorie diet (LCD). Design Randomized double-blind parallel-group clinical trial Methods Forty-six obese women were randomly assigned to the metformin (500 mg/tab) or placebo groups using computer-generated random numbers. Subjects in both groups took two tablets per day for 2 months. Anthropometric measurements and collection of blood and fecal samples were done at the baseline and at the end of the trial. Gut microbiota composition was assessed using 16S rRNA amplicon sequencing. Results Twenty-four and twenty-two subjects were included in the metformin + LCD and placebo + LCD groups, respectively; at the end of trial, 20 and 16 subjects were analyzed. The metformin + LCD and placebo + LCD caused a 4.5 and 2.6% decrease in BMI from the baseline values, respectively (P < 0.01). Insulin concentration decreased in the metformin + LCD group (P = 0.046). The overall fecal microbiota composition and diversity were unaffected in the metformin + LCD group. However, a significant specific increase in Escherichia/Shigella abundance was observed after metformin + LCD intervention (P = 0.026). Fecal acetate concentration, but not producers, was significantly higher in the placebo + LCD group, adjusted for baseline values and BMI (P = 0.002). Conclusions Despite the weight reduction after metformin intake, the overall fecal microbiota composition remained largely unchanged in obese women, with exception of changes in specific proteobacterial groups.


2020 ◽  
Vol 34 (5) ◽  
pp. 650-660 ◽  
Author(s):  
Xiang Liu ◽  
Jing Tao ◽  
Jing Li ◽  
Xiaolin Cao ◽  
Yong Li ◽  
...  

Background The gut microbiota plays an important role in shaping the immune system and may be closely connected to the development of allergic diseases. Objective This study aimed to determine the gut microbiota composition in Chinese allergic rhinitis (AR) patients as compared with healthy controls (HCs). Methods We collected stool samples from 93 AR patients and 72 age- and sex-matched HCs. Gut microbiota composition was analyzed using QIIME targeting the 16S rRNA gene. Functional pathways were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. Statistical analysis was performed using the R program, linear discriminant analysis effect size (LefSe), analysis of QIIME, and statistical analysis of metagenomic profiles, among other tests. Results Compared with HCs, AR patients had significantly lower gut-microbiota α-diversity ( P < .001). The gut microbiota composition significantly differed between the 2 study groups. At the phylum level, the relative abundance of Bacteroidetes was higher while those of Actinobacteria and Proteobacteria were lower in the AR group than in the HC group ( P < .001, q < 0.001). At the genus level, Escherichia-Shigella, Prevotella, and Parabacteroides ( P < .001, q < 0.001) had significantly higher relative abundances in the AR group than in the HC group. LefSe analysis indicated that Escherichia-Shigella, Lachnoclostridium, Parabacteroides, and Dialister were potential biomarkers for AR. In addition, predictive metagenome functional analysis showed that pyruvate, porphyrin, chlorophyll, purine metabolism, and peptidoglycan biosynthesis significantly differed between the AR and HC groups. Conclusion A comparison of the gut microbiota of AR patients and HCs suggested that dysbiosis of the fecal microbiota is involved in the development of AR. The present results may reveal key differences and identify targets for preventive or therapeutic intervention.


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