scholarly journals Fecal microbiota dynamics during disease activity and remission in newly diagnosed and established ulcerative colitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lena Öhman ◽  
Anders Lasson ◽  
Anna Strömbeck ◽  
Stefan Isaksson ◽  
Marcus Hesselmar ◽  
...  

AbstractPatients with ulcerative colitis (UC) have an altered gut microbiota composition, but the microbial relationship to disease activity needs to be further elucidated. Therefore, temporal dynamics of the fecal microbial community during remission and flare was determined. Fecal samples were collected at 2–6 time-points from UC patients during established disease (cohort EST) and at diagnosis (cohort NEW). Sampling range for cohort EST was 3–10 months and for cohort NEW 36 months. Relapses were monitored for an additional three years for cohort EST. Microbial composition was assessed by Genetic Analysis GA-map Dysbiosis Test, targeting ≥ 300 bacteria. Eighteen patients in cohort EST (8 with maintained remission and 10 experiencing a flare), provided 71 fecal samples. In cohort NEW, 13 patients provided 49 fecal samples. The microbial composition showed no clustering related to disease activity in any cohort. Microbial dissimilarity was higher between than within patients for both cohorts, irrespective of presence of a flare. Microbial stability within patients was constant over time with no major shift in overall composition nor modification in the abundance of any specific species. Microbial composition was not affected by intensified medical treatment or linked to future disease course. Thus in UC, the gut microbiota is highly stable irrespective of disease stage, disease activity or treatment escalation. This suggests that prolonged dietary interventions or repeated fecal transplantations are needed to be able to induce permanent alterations of the gut microbiota.

2021 ◽  
Author(s):  
Lena Öhman ◽  
Anders Lasson ◽  
Anna Strömbeck ◽  
Stefan Isaksson ◽  
Marcus Hesselmar ◽  
...  

Abstract Patients with ulcerative colitis (UC) have an altered gut microbiota composition, but the microbial relationship to disease activity needs to be further elucidated. Therefore, temporal dynamics of the fecal microbial community during remission and flare was determined. Fecal samples were collected at 2–6 time-points from UC patients during established disease (cohort EST) and at diagnosis (cohort NEW). Sampling range for cohort EST was 3–10 months and for cohort NEW 36 months. Relapses were monitored for an additional three years for cohort EST. Microbial composition was assessed by Genetic Analysis GA-map™ Dysbiosis test, targeting ≥ 300 bacteria. Eighteen patients in cohort EST (8 with maintained remission and 10 experiencing a flare), provided 71 fecal samples. In cohort NEW, 13 patients provided 49 fecal samples. The microbial composition showed no clustering related to disease activity in any cohort. Microbial dissimilarity was higher between than within patients for both cohorts, irrespective of presence of a flare. Microbial stability within patients was constant over time with no major shift in overall composition nor modification in the abundance of any specific species. Microbial composition was not affected by intensified medical treatment or linked to future disease course. Thus in UC, the gut microbiota is highly stable irrespective of disease stage, disease activity or treatment escalation. This suggests that prolonged dietary interventions or repeated fecal transplantations are needed to be able to induce permanent alterations of the gut microbiota.


2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 268-269
Author(s):  
H J Galipeau ◽  
A CAMINERO FERNANDEZ ◽  
W Turpin ◽  
M Bermudez-Brito ◽  
A Santiago ◽  
...  

Abstract Background Altered gut microbiota composition and function has been associated with inflammatory bowel diseases (IBD) including ulcerative colitis (UC), but causality and mechanisms remain unknown. Most studies have examined patients with active or treated disease and little is known about microbial compositional or functional changes that occur before disease onset. Aims We studied a longitudinal cohort of subjects at risk for IBD to define the fecal microbial composition and function in subjects prior to UC onset (pre-UC) and at diagnosis (post-UC), and in matched at-risk subjects that remained healthy. Methods Fecal samples were collected from healthy individuals at-risk for IBD (pre-UC; n=13) and subjects were followed longitudinally until UC diagnosis (post-UC, n=9), at which point another fecal sample was collected. Fecal samples from a cohort of matched at-risk individuals that did not develop UC were used as healthy controls (n=48). We applied 16S rRNA gene sequencing, next generation shotgun sequencing, in vitro proteolytic assays and gnotobiotic colonizations to define the microbial composition and proteolytic function in fecal samples. Results The microbiota of post-UC subjects clustered separately from pre-UC and HC subjects, based on bray-curtis and unweighted UniFrac, had reduced alpha-diversity, and had reduced abundance of Aldercreutzia compared to pre-UC and HC. In vitro functional analysis revealed increased fecal proteolytic and elastase activity in pre-UC and post-UC samples compared to HC. Metagenomics identified pathways and gene families related to protein metabolism and proteases/peptides that were significantly different between HC and pre-UC samples, suggesting a bacterial component to the pre-UC proteolytic signature. Elastase activity inversely correlated with the relative abundance of Adlercreutzia, and other potentially beneficial taxa, and directly correlated with Bacteroides vulgatus, a known proteolytic taxon. High elastase activity was confirmed in Bacteroides isolates from fecal samples. Bacterial contribution and functional significance of the proteolytic signature was investigated in germ-free adults and litters born from dams colonized with HC, pre-UC or post-UC microbiota. Mice colonized with pre-UC microbiota at adulthood or neonatally developed higher fecal proteolytic activity and an inflammatory immune tone compared with HC colonized mice. Conclusions We have identified increased fecal proteolytic activity that precedes clinical diagnosis of UC and associates with gut microbiota changes. This may constitute a non-invasive biomarker of inflammation to monitor at-risk populations that can be targeted therapeutically with anti-proteases. Funding Agencies CAG, CCC, CIHR


2019 ◽  
Vol 8 (1) ◽  
pp. 60
Author(s):  
Mohd Baasir Gaisawat ◽  
Chad W. MacPherson ◽  
Julien Tremblay ◽  
Amanda Piano ◽  
Michèle M. Iskandar ◽  
...  

Clostridium (C.) difficile-infection (CDI), a nosocomial gastrointestinal disorder, is of growing concern due to its rapid rise in recent years. Antibiotic therapy of CDI is associated with disrupted metabolic function and altered gut microbiota. The use of probiotics as an adjunct is being studied extensively due to their potential to modulate metabolic functions and the gut microbiota. In the present study, we assessed the ability of several single strain probiotics and a probiotic mixture to change the metabolic functions of normal and C. difficile-infected fecal samples. The production of short-chain fatty acids (SCFAs), hydrogen sulfide (H2S), and ammonia was measured, and changes in microbial composition were assessed by 16S rRNA gene amplicon sequencing. The C. difficile-infection in fecal samples resulted in a significant decrease (p < 0.05) in SCFA and H2S production, with a lower microbial alpha diversity. All probiotic treatments were associated with significantly increased (p < 0.05) levels of SCFAs and restored H2S levels. Probiotics showed no effect on microbial composition of either normal or C. difficile-infected fecal samples. These findings indicate that probiotics may be useful to improve the metabolic dysregulation associated with C. difficile infection.


2020 ◽  
Vol 41 (05) ◽  
pp. 292-299 ◽  
Author(s):  
Jarrad Timothy Hampton-Marcell ◽  
Tifani W. Eshoo ◽  
Marc D. Cook ◽  
Jack A. Gilbert ◽  
Craig A. Horswill ◽  
...  

AbstractExercise can influence gut microbial community structure and diversity; however, the temporal dynamics of this association have rarely been explored. Here we characterized fecal microbiota in response to short term changes in training volume. Fecal samples, body composition, and training logs were collected from Division I NCAA collegiate swimmers during peak training through their in-season taper in 2016 (n=9) and 2017 (n=7), capturing a systematic reduction in training volume near the conclusion of their athletic season. Fecal microbiota were characterized using 16S rRNA V4 amplicon sequencing and multivariate statistical analysis, Spearman rank correlations, and random forest models. Peak training volume, measured as swimming distance, decreased significantly during the study period from 32.6±4.8 km/wk to 11.3±8.1 km/wk (ANOVA, p<0.05); however, body composition showed no significant changes. Coinciding with the decrease in training volume, the microbial community structure showed a significant decrease in overall microbial diversity, a decrease in microbial community structural similarity, and a decrease in the proportion of the bacterial genera Faecalibacterium and Coprococcus. Together these data demonstrate a significant association between short-term changes in training volume and microbial composition and structure in the gut; future research will establish whether these changes are associated with energy balance or nutrient intake.


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.


Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 744 ◽  
Author(s):  
Jose Jaimes ◽  
Veronika Jarosova ◽  
Ondrej Vesely ◽  
Chahrazed Mekadim ◽  
Jakub Mrazek ◽  
...  

Dietary phenolics or polyphenols are mostly metabolized by the human gut microbiota. These metabolites appear to confer the beneficial health effects attributed to phenolics. Microbial composition affects the type of metabolites produced. Reciprocally, phenolics modulate microbial composition. Understanding this relationship could be used to positively impact health by phenolic supplementation and thus create favorable colonic conditions. This study explored the effect of six stilbenoids (batatasin III, oxyresveratrol, piceatannol, pinostilbene, resveratrol, thunalbene) on the gut microbiota composition. Stilbenoids were anaerobically fermented with fecal bacteria from four donors, samples were collected at 0 and 24 h, and effects on the microbiota were assessed by 16S rRNA gene sequencing. Statistical tests identified affected microbes at three taxonomic levels. Observed microbial composition modulation by stilbenoids included a decrease in the Firmicutes to Bacteroidetes ratio, a decrease in the relative abundance of strains from the genus Clostridium, and effects on the family Lachnospiraceae. A frequently observed effect was a further decrease of the relative abundance when compared to the control. An opposite effect to the control was observed for Faecalibacterium prausnitzii, whose relative abundance increased. Observed effects were more frequently attributed to resveratrol and piceatannol, followed by thunalbene and batatasin III.


2021 ◽  
Vol 8 ◽  
Author(s):  
Zongwei Li ◽  
Zhengpeng Li ◽  
Liying Zhu ◽  
Ning Dai ◽  
Gang Sun ◽  
...  

Gut microbiota dysbiosis is closely associated with ulcerative colitis (UC). Prebiotic therapy is a potential approach for UC management especially remission maintaining. Xylo-oligosaccharide (XOS) is an efficient prebiotic with proven health benefits and few side effects. However, the effects of XOS on the gut microbiota of patients with UC have not been investigated previously. The aim of this study was to evaluate the prebiotic effects of XOS on the fecal microbiota of patients with UC in clinical remission using an in vitro fermentation model. Five patients with UC in clinical remission and five healthy volunteers were enrolled in this study. Fresh fecal samples of UC patients were diluted and inoculated in yeast extract, casitone and fatty acid (YCFA) medium alone or with XOS. After fermentation for 48 h, samples were collected for 16S rDNA sequencing to investigate the gut microbiota composition. Differences in the gut microbiota between healthy volunteers and UC patients in clinical remission were detected using original fecal samples. Subsequently, the differences between the YCFA medium alone or with XOS samples were analyzed to illustrate the effects of XOS on the gut microbiota of UC patients. In both principal coordinate analysis (PCoA) and principal component analysis (PCA), the fecal samples of UC patients differed from those of healthy volunteers. Linear discriminant analysis effect size (LEfSe) analysis revealed that the relative abundances of g_Roseburia and g_Lachnospiraceae_ND3007_group were higher in healthy volunteers than in UC patients, while o_Lactobacillales abundance showed the opposite trend (P &lt; 0.05). Wilcoxon rank-sum test bar plot showed that the abundances of g_Eubacterium_halli_group and g_Lachnospiraceae_ND3007_group were higher in the healthy volunteers than in the UC patients (P &lt; 0.05). In addition, in UC patients, the Wilcoxon rank-sum test showed that XOS fermentation promoted the growth of bacterial groups including g_Roseburia, g_Bifidobacterium, and g_Lactobacillus, which is beneficial for recovery of intestinal diseases. These results suggest that XOS can relieve dysbiosis in the feces of UC patients in clinical remission and thus represent a potential prebiotic material for maintaining remission.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ayako Horigome ◽  
Ken Hisata ◽  
Toshitaka Odamaki ◽  
Noriyuki Iwabuchi ◽  
Jin-zhong Xiao ◽  
...  

The colonization and persistence of probiotics introduced into the adult human gut appears to be limited. It is uncertain, however, whether probiotics can successfully colonize the intestinal tracts of full-term and premature infants. In this study, we investigated the colonization and the effect of oral supplementation with Bifidobacterium breve M-16V on the gut microbiota of low birth weight (LBW) infants. A total of 22 LBW infants (12 infants in the M-16V group and 10 infants in the control group) were enrolled. B. breve M-16V was administrated to LBW infants in the M-16V group from birth until hospital discharge. Fecal samples were collected from each subject at weeks (3.7–9.3 weeks in the M-16V group and 2.1–6.1 weeks in the control group) after discharge. qPCR analysis showed that the administrated strain was detected in 83.3% of fecal samples in the M-16V group (at log10 8.33 ± 0.99 cell numbers per gram of wet feces), suggesting that this strain colonized most of the infants beyond several weeks post-administration. Fecal microbiota analysis by 16S rRNA gene sequencing showed that the abundance of Actinobacteria was significantly higher (P &lt; 0.01), whereas that of Proteobacteria was significantly lower (P &lt; 0.001) in the M-16V group as compared with the control group. Notably, the levels of the administrated strain and indigenous Bifidobacterium bacteria were both significantly higher in the M-16V group than in the control group. Our findings suggest that oral administration of B. breve M-16V led to engraftment for at least several weeks post-administration and we observed a potential overall improvement in microbiota formation in the LBW infants’ guts.


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.


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