The Effectiveness of Multi-Session FMT Treatment in Active Ulcerative Colitis Patients: A Pilot Study

Mańkowska-Wierzbicka, Dorota; Stelmach-Mardas, Marta; Gabryel, Marcin; Tomczak, Hanna; Skrzypczak-Zielińska, Marzena; Zakerska-Banaszak, Oliwia; Sowińska, Anna; Mahadea, Dagmara; Baturo, Alina; Wolko, Łukasz; Słomski, Ryszard; Dobrowolska, Agnieszka

doi:10.3390/biomedicines8080268

Cited by 22 publications

(22 citation statements)

References 75 publications

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“…Consistent with our results, increases in the caecal contents of Coprococcus were identified in rats supplemented with iron, which were suggested to mediate oxidative stress and histopathological alterations observed in the liver of these animals [ 14 ]. Also in agreement with our results, low serum ferritin concentrations coexisted with decreased abundance of Veillonella species in ulcerative colitis patients receiving FMT from healthy donors [ 15 ], while Veillonella genus abundance was dose-dependently enriched after improvement of steatosis in NASH patients [ 16 ] . In addition, those with > 70% reduction in liver fat had a trend towards reduction of Methanobrevibacter , which we also found negatively associated with serum ferritin levels.…”

Section: Discussionsupporting

confidence: 90%

Iron status influences non-alcoholic fatty liver disease in obesity through the gut microbiome

et al. 2021

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Background The gut microbiome and iron status are known to play a role in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), although their complex interaction remains unclear. Results Here, we applied an integrative systems medicine approach (faecal metagenomics, plasma and urine metabolomics, hepatic transcriptomics) in 2 well-characterised human cohorts of subjects with obesity (discovery n = 49 and validation n = 628) and an independent cohort formed by both individuals with and without obesity (n = 130), combined with in vitro and animal models. Serum ferritin levels, as a markers of liver iron stores, were positively associated with liver fat accumulation in parallel with lower gut microbial gene richness, composition and functionality. Specifically, ferritin had strong negative associations with the Pasteurellaceae, Leuconostocaceae and Micrococcaea families. It also had consistent negative associations with several Veillonella, Bifidobacterium and Lactobacillus species, but positive associations with Bacteroides and Prevotella spp. Notably, the ferritin-associated bacterial families had a strong correlation with iron-related liver genes. In addition, several bacterial functions related to iron metabolism (transport, chelation, heme and siderophore biosynthesis) and NAFLD (fatty acid and glutathione biosynthesis) were also associated with the host serum ferritin levels. This iron-related microbiome signature was linked to a transcriptomic and metabolomic signature associated to the degree of liver fat accumulation through hepatic glucose metabolism. In particular, we found a consistent association among serum ferritin, Pasteurellaceae and Micrococcacea families, bacterial functions involved in histidine transport, the host circulating histidine levels and the liver expression of GYS2 and SEC24B. Serum ferritin was also related to bacterial glycine transporters, the host glycine serum levels and the liver expression of glycine transporters. The transcriptomic findings were replicated in human primary hepatocytes, where iron supplementation also led to triglycerides accumulation and induced the expression of lipid and iron metabolism genes in synergy with palmitic acid. We further explored the direct impact of the microbiome on iron metabolism and liver fact accumulation through transplantation of faecal microbiota into recipient’s mice. In line with the results in humans, transplantation from ‘high ferritin donors’ resulted in alterations in several genes related to iron metabolism and fatty acid accumulation in recipient’s mice. Conclusions Altogether, a significant interplay among the gut microbiome, iron status and liver fat accumulation is revealed, with potential significance for target therapies.

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Section: Discussionsupporting

confidence: 90%

Iron status influences non-alcoholic fatty liver disease in obesity through the gut microbiome

et al. 2021

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“…Moreover, we only treated UC patients with 2-3 FMT and monitored patients at 3 months post-FMT. Given that recent studies have shown that frequent FMT and continual monitoring of patients for 6 months are feasible and valuable (Paramsothy et al, 2019;Mañkowska-Wierzbicka et al, 2020), we should consider more frequent FMT for UC patients and extend our longitudinal studies for a longer period. Finally, we did not analyze colonic tissues histologically, intestinal barrier function, and inflammatory measures in those UC patients, which might miss important information on the action of FMT in UC patients.…”

Section: Discussionmentioning

confidence: 99%

Cross-Talk Between Butyric Acid and Gut Microbiota in Ulcerative Colitis Following Fecal Microbiota Transplantation

Huang

et al. 2021

Front. Microbiol.

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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.

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“…A fully explained pathogenesis of UC could be a milestone in the development of effective targeted therapy, as faecal microbiota transplantation (FMT) has recently promised to be 33 . Our recent pilot investigation concerning FMT in UC patients has proved a strong correlation between specific gut bacteria and clinical parameters in the FMT procedure determining its effectiveness 34 . Thus detailed knowledge about the microbiome of a healthy population is needed and our analysis of UC microbiota in Polish patients will constitute an important basis for therapeutic options and further research on UC.…”

Section: Introductionmentioning

confidence: 99%

Dysbiosis of gut microbiota in Polish patients with ulcerative colitis: a pilot study

Zakerska-Banaszak

Tomczak

Gabryel

et al. 2021

Sci Rep

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Ulcerative colitis (UC) is a chronic immune-mediated disorder, whose etiology is not fully understood and for which no effective treatment is available. Recently, research has focused on the dysbiosis of gut microbiome in UC. However, the results so far remain inconsistent and insufficient to understand the microbial component in UC pathogenesis. In this study, we determine specific changes in the gut microbial profile in Polish UC patients compared to healthy subjects for the first time. Using 16S rRNA gene-based analysis we have described the intestinal microbial community in a group of 20 individuals (10 UC patients and 10 controls). Our results after multiple hypothesis testing correction demonstrated substantially lower gut microbiome diversity in UC cases compared to the controls and considerable differences at the phylum level, as well as among 13 bacterial families and 20 bacterial genera (p < 0.05). UC samples were more abundant in Proteobacteria (8.42%), Actinobacteria (6.89%) and Candidate Division TM7 (2.88%) than those of healthy volunteers (2.57%, 2.29% and 0.012%, respectively). On the other hand, Bacteroidetes and Verrucomicrobia were presented at a lower level in UC relative to the controls (14% and 0% vs 27.97% and 4.47%, respectively). In conclusion, our results show a reduced gut microbial diversity in Polish UC patients, a reduction of taxa with an anti-inflammatory impact and an increased abundance of potentially pathogenic bacteria.

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The Effectiveness of Multi-Session FMT Treatment in Active Ulcerative Colitis Patients: A Pilot Study

Cited by 22 publications

References 75 publications

Iron status influences non-alcoholic fatty liver disease in obesity through the gut microbiome

Iron status influences non-alcoholic fatty liver disease in obesity through the gut microbiome

Cross-Talk Between Butyric Acid and Gut Microbiota in Ulcerative Colitis Following Fecal Microbiota Transplantation

Dysbiosis of gut microbiota in Polish patients with ulcerative colitis: a pilot study

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