scholarly journals Changes in the Intestinal Microbiota of Patients with Inflammatory Bowel Disease with Clinical Remission during an 8-Week Infliximab Infusion Cycle

2020 ◽  
Vol 8 (6) ◽  
pp. 874
Author(s):  
Gyeol Seong ◽  
Namil Kim ◽  
Je-Gun Joung ◽  
Eun Ran Kim ◽  
Dong Kyung Chang ◽  
...  

This study investigated changes in the intestinal microbiota during 8-week infliximab maintenance therapy in inflammatory bowel disease (IBD) patients in clinical remission. Microbial compositional differences were analyzed according to the trough level of infliximab (TLI) and mucosal healing (MH) status. 16S rRNA gene-based microbiome profiling was performed on 10 and 74 fecal samples from 10 healthy volunteers and 40 adult IBD patients, respectively. Fecal sampling occurred at 1–2 weeks (1W) and 7–8 weeks (7W) after infliximab infusion. TLI was measured by ELISA at 8 weeks, immediately before the subsequent infusion; MH was evaluated by endoscopy within 3 months. There were no significant changes in microbial composition, species richness, or diversity indices between 1W and 7W. However, 7W samples from the patients with TLI ≥ 5 μg/mL showed an increased species richness compared with patients with TLI < 5 μg/mL, and patients with MH showed increased diversity compared with non-MH patients. Beta-diversity analysis showed clustering between samples in the MH and non-MH groups. LEfSe analysis identified differential composition of Faecalibacterium prausnitzii group according to TLI and MH. In conclusion, these results suggest the potential of fecal microbiota as a response indicator.

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S649-S649
Author(s):  
G Seong ◽  
J H Song ◽  
J Shin ◽  
S M Kong ◽  
E R Kim ◽  
...  

Abstract Background This study investigated changes in the intestinal microbiota during 8-week infliximab maintenance therapy in inflammatory bowel disease (IBD) patients with clinical remission. Microbial compositional differences were analysed according to the trough level of infliximab (TLI) and mucosal healing (MH) status. Methods 16S rRNA gene-based microbiome profiling was performed on 10 and 74 faecal samples from 10 healthy volunteers and 40 adult IBD patients, respectively. All enrolled IBD patients were in clinical remission during infliximab maintenance therapy. To identify changes in the intestinal microbiota, faecal sampling occurred at 1–2 weeks (1W) and 7–8 weeks (7W) after infliximab infusion. TLI was measured by ELISA at 8 weeks immediately before the subsequent infusion; MH was evaluated by endoscopy within 3 months. Results No significant differences were found in microbial composition, species richness, and diversity indices between 1W and 7W samples or in microbial composition and diversity between healthy volunteer and 1W or 7W samples. However, 7W faecal samples from the patients with TLI≥5 μg/ml showed increased species richness compared with TLI&lt;5 μg/ml, and patients with MH showed increased species diversity compared with non-MH. Beta-diversity analysis showed clustering between samples in the MH and non-MH groups. LefSe analysis identified differential expression of Faecalibacterium prausnitzii group between TLI &lt; 5 μg/ml and TLI ≥ 5 μg/ml and MH and non-MH groups. Conclusion There were no significant changes in the intestinal microbiota during an 8-week infliximab infusion cycle in IBD patients with clinical remission; however, microbial composition, species richness, and diversity were associated with TLI and MH status.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S010-S011
Author(s):  
E Brand ◽  
Y Laenen ◽  
F van Wijk ◽  
M de Zoete ◽  
B Oldenburg

Abstract Background The pathogenesis of inflammatory bowel disease (IBD) is thought to result from an interplay between microbiota, the immune system and the environment in genetically susceptible hosts. Immunoglobulin A (IgA) produced by the immune system can be specifically directed against bacteria. The IgA-coating pattern of intestinal bacteria thus reflects interactions between the immune system and specific bacteria. Studying IBD in twins, concordant and discordant for IBD, reduces the impact of genetic predisposition and childhood exposures and therefore offers the unique opportunity to focus on other factors such as intestinal microbiota composition and immune-interactions in IBD. Methods Faecal samples from twin pairs discordant for Crohn’s disease (CD) or ulcerative colitis (UC) were collected. Employing fluorescence-activated cell sorting, IgA+ and IgA− bacteria from the intestinal microbiota were sorted. Subsequently, (1) the total, (2) IgA+ and (3) IgA− microbial composition was determined by 16S rRNA sequencing (IgA-SEQ). We estimated the relative IgA coating per bacterial species by dividing the abundance of that species in the IgA+ fraction over the abundance in the IgA- fraction, representing the IgA coating index. Linear discriminant analyses were performed with LefSE. Results We included 31 twin pairs (62 individuals) discordant for IBD (CD: 15, UC: 16). 15/32 twin pairs were monozygotic, 43/62 of participants were female, the median age was 47 years (interquartile range: 34–58.5). Of 31 participants with IBD, 7 had signs of active inflammation based on endoscopy, Harvey–Bradshaw index or short clinical colitis activity index. Differences (log-linear discriminant analysis score &gt;3) in the microbial composition of IgA-coated bacteria were observed between CD patients and their twin-siblings not affected by IBD: Dorea formicigenerans (increased in IgA coating), Parabacteroides sp., Christensenellaceae sp., Clostridium sp. and Mollicutes RF39 sp. (decreased in IgA coating). In ulcerative colitis patients, an increase in IgA-coating was observed for Ruminococcus gnavus and Dorea formicigenerans, while Turicibacter sp., Barnesiellaceae sp. and an unclassified Clostridiales sp. were decreased in IgA-coating compared with their twin-siblings not affected by IBD. Conclusion In twins affected by IBD, the pattern of IgA-coated bacteria differs between IBD and non-IBD affected individuals. These data on immune-bacteria interactions could serve as a starting point for the elucidation of the immune-responses triggered by specific bacteria in IBD.


2020 ◽  
Vol 158 (6) ◽  
pp. S-700-S-701
Author(s):  
Gyeol Seong ◽  
Joo Hye Song ◽  
Jongbeom Shin ◽  
Sung min Kong ◽  
Jong-In Chang ◽  
...  

Author(s):  
Renate A A A Ruigrok ◽  
Valerie Collij ◽  
Paula Sureda ◽  
Marjolein A Y Klaassen ◽  
Laura A Bolte ◽  
...  

Abstract Background and Aims The human gastrointestinal tract harbours distinct microbial communities essential for health. Little is known about small intestinal communities, despite the small intestine playing a fundamental role in nutrient absorption and host-microbe immune homeostasis. We aimed to explore the small intestine microbial composition and metabolic potential, in the context of inflammatory bowel disease (IBD). Methods Metagenomes derived from faecal samples and extensive phenotypes were collected from 57 individuals with an ileostomy or ileoanal pouch, and compared with 1178 general population and 478 IBD faecal metagenomes. Microbiome features were identified using MetaPhAn2 and HUMAnN2, and association analyses were performed using multivariate linear regression. Results Small intestinal samples had a significantly lower bacterial diversity, compared with the general population and, to a lesser extent, IBD samples. Comparing bacterial composition, small intestinal samples clustered furthest from general population samples and closest to IBD samples with intestinal resections. Veillonella atypica, Streptococcus salivarius and Actinomyces graevenitzii were among the species significantly enriched in the small intestine. Predicted metabolic pathways in the small intestine are predominantly involved in simple carbohydrate and energy metabolism, but also suggest a higher proinflammatory potential. Conclusion We described the bacterial composition and metabolic potential of the small intestinal microbiota. The colonic microbiome of IBD patients, particularly with intestinal resections, showed resemblance to that of the small intestine. Moreover, several features characterising the small intestinal microbiome have been previously associated with IBD. These results highlight the importance of studying the small intestinal microbiota to gain new insight into disease pathogenesis.


2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S59-S59
Author(s):  
Sumona Bhattacharya ◽  
Beatriz Marciano ◽  
Harry Malech ◽  
Steven Holland ◽  
Suk See De Ravin ◽  
...  

Abstract Introduction Chronic granulomatous disease (CGD) is a rare immunodeficiency caused by mutations in the NADPH oxidase complex. Dysregulated immune function may cause inflammatory bowel disease (IBD). Patients with CGD-associated IBD may not respond to or may develop serious infections as a result of traditional IBD therapies such as vedolizumab and infliximab. Ustekinumab is approved for use in Crohn’s disease and ulcerative colitis however there is scarce data on its efficacy and safety in CGD. Aims To evaluate the efficacy and safety of ustekinumab for CGD-associated IBD. Methods A retrospective chart review was conducted on CGD patients followed at a single center who had consented to participate in a natural history study. Clinical, laboratory, and endoscopic data were extracted in those that had received ustekinumab for IBD. Results Eight patients were found. Four were male and four were female. Five were white, one was Asian, one was black, and one was mixed race. Median age at diagnosis of CGD was 3 years (IQR 8) and of IBD was 15.5 years (IQR 20). Median age at initiation of ustekinumab was 27.5 years (IQR 14) and median duration on ustekinumab was 10 months (IQR 7). Six had colonic disease, two had ileocolonic disease, and six had perianal disease. Six failed other biologics (n=5 for vedolizumab, n=1 for infliximab, n=1 for adalimumab). Six patients symptomatically improved whereas two had no improvement. Changes in hemoglobin and C-reactive protein were equivocal. Three patients had improved endoscopic findings, two had unimproved findings, and three patients lacked this data. Overall, four patients achieved clinical remission. However, none of the five patients with endoscopic reevaluation achieved endoscopic remission. Three patients discontinued therapy due to lack of response: two required surgery and one underwent stem cell transplant. Fungal pneumonia (n=2), otitis media (n=1), oral herpes simplex virus 1 (n=1), and viral gastroenteritis (n=1) were reported. One infusion reaction occurred. Discussion In our cohort of eight patients with CGD-associated IBD receiving ustekinumab, results were mixed with four patients experiencing some degree of clinical or endoscopic improvement including four who achieved clinical remission. Multiple CGD-related variables may account for the mixed laboratory findings. Four of the five patients with endoscopic reevaluation had pre-existing strictures that would be unlikely to reverse with medical therapy alone. Of these, two had otherwise resolved endoscopic inflammation. Only two patients had no endoscopic improvement. Two serious infections occurred however CGD confers increased infectious susceptibility and no infections lead to discontinuation of therapy. Given these promising results, further formalized study of ustekinumab in CGD-associated IBD is needed.


2017 ◽  
Vol 190 (3) ◽  
pp. 394-405 ◽  
Author(s):  
E. Nissilä ◽  
K. Korpela ◽  
A. I. Lokki ◽  
R. Paakkanen ◽  
S. Jokiranta ◽  
...  

2015 ◽  
Vol 81 (21) ◽  
pp. 7582-7592 ◽  
Author(s):  
Mireia Lopez-Siles ◽  
Margarita Martinez-Medina ◽  
Carles Abellà ◽  
David Busquets ◽  
Miriam Sabat-Mir ◽  
...  

ABSTRACTFaecalibacterium prausnitziidepletion in intestinal diseases has been extensively reported, but little is known about intraspecies variability. This work aims to determine if subjects with gastrointestinal disease host mucosa-associatedF. prausnitziipopulations different from those hosted by healthy individuals. A new species-specific PCR-denaturing gradient gel electrophoresis (PCR-DGGE) method targeting the 16S rRNA gene was developed to fingerprintF. prausnitziipopulations in biopsy specimens from 31 healthy control (H) subjects and 36 Crohn's disease (CD), 23 ulcerative colitis (UC), 6 irritable bowel syndrome (IBS), and 22 colorectal cancer (CRC) patients. The richness ofF. prausnitziisubtypes was lower in inflammatory bowel disease (IBD) patients than in H subjects. The most prevalent operational taxonomic units (OTUs) consisted of four phylotypes (OTUs with a 99% 16S rRNA gene sequence similarity [OTU99]), which were shared by all groups of patients. Their distribution and the presence of some disease-specificF. prausnitziiphylotypes allowed us to differentiate the populations in IBD and CRC patients from that in H subjects. At the level of a minimum similarity of 97% (OTU97), two phylogroups accounted for 98% of the sequences. Phylogroup I was found in 87% of H subjects but in under 50% of IBD patients (P= 0.003). In contrast, phylogroup II was detected in >75% of IBD patients and in only 52% of H subjects (P= 0.005). This study reveals that even though the main members of theF. prausnitziipopulation are present in both H subjects and individuals with gut diseases, richness is reduced in the latter and an altered phylotype distribution exists between diseases. This approach may serve as a basis for addressing the suitability ofF. prausnitziiphylotypes to be quantified as a putative biomarker of disease and depicting the importance of the loss of these subtypes in disease pathogenesis.


2021 ◽  
Author(s):  
Xiufang Cui ◽  
Haiyang Wang ◽  
Ziping Ye ◽  
Yi Li ◽  
Xinyun Qiu ◽  
...  

Abstract BACKGROUND: The intestinal microbiota is thought to be involved in the occurrence of Inflammatory Bowel Disease in remission (IBDR) with Irritable Bowel Syndrome (IBS)-type symptoms, but the specific distinct profile of these bacteria remains unclear. Therefore, the purpose of this research is to investigate this issue by conducting a cross-sectional study.METHODS: IBS patients were diagnosed according to Rome Ⅳ criteria, IBD diagnosed according to the criteria of European Crohn & Colitis Organization (ECCO), IBDR patients with IBS-type symptoms were defined according to related IBS-type symptoms meeting the Rome IV criteria in IBDR patients, and were included Crohn’s disease in remission (CDR) and ulcerative colitis in remission (UCR) based on Crohn’s Disease Activity Index (DAI) and Mayo Scoring System respectively. Healthy controls come from the physical examination center and exclude people with underlying diseases. All enrolled subjects were divided into six groups, as followed: Health Control, IBS, CDR with IBS-type symptoms (CDR-IBS+), CDR without IBS-type symptoms (CDR-IBS-), UCR-IBS+ and UCR-IBS-. We collected fresh fecal samples from all subjects and applied 16S rRNA sequencing analysis to detect the structure and diversity of the microbiota among different groups. RESULTS: A total of 97 subjects were included in this study, of which 18 were health controls, 34 IBS patients, 25 CDR and 20 UCR. The richness of intestinal microbiota in CDR-IBS-was significantly lower than that in the control and IBS groups based on the analysis of observed species and Chao index (P<0.05). The observed species index in CDR-IBS+ was significantly higher than CDR-IBS- group (median index: 254.8 vs 203, P=0.036). No difference was found in Alpha diversity between UCR-IBS+ and UCR-IBS-. At phylum level, there was no significant difference between UC or CD with IBS-type symptoms and those without related symptoms. At genus level, the number of Faecalibacterium in CDR-IBS+ increased significantly while Fusobacterium decreased compared with CDR-IBS-(mean relative abundance of Faecalibacterium: 20.35% vs 5.18%, P<0.05; Fusobacterium: 1.51% vs 5.2%, P<0.05). However, compared with UCR-IBS - group, the number of Faecalibacterium in UCR-IBS+ group decreased, while the number of Streptococcus increased, but there was no statistical difference in the genus structure. Regardless of the phylum or genus level, the abundance and composition of the microbiota of IBS patients were not distinct from those of healthy people.CONCLUSIONS: CD patients in remission with IBS-type symptoms may be related to the increase of Faecalibacterium and decrease of Fusobacterium. UC patients in remission with IBS-type symptoms cannot be explained by changes in the abundance and structure of intestinal microbiota from our across-sectional study.


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