scholarly journals DOP71 Fungal and bacterial gut microbiota in paediatric onset Inflammatory Bowel Disease introduced to infliximab

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S105-S105
Author(s):  
R Ventin-Holmberg ◽  
M Höyhtyä ◽  
S Saqib ◽  
K Korpela ◽  
A Nikkonen ◽  
...  

Abstract Background Paediatric Inflammatory Bowel Disease (PIBD), including Crohn’s Disease (CD), Ulcerative Colitis (UC) and IBD undefined (IBDU) is increasing worldwide and is characterized by an onset inflammation in the gastrointestinal tract. The patients may present severe symptoms such as abdominal pain, diarrhoea and bloody stool. No defined pathogenesis has been established for PIBD, but an imbalanced intestinal microbiota is strongly associated to the disease. Anti-tumour necrosis factor alpha (TNF-α) is an effective drug to treat inflammation in IBD, but up to half of the patients do not have a long-term response to the drug. Presently, there are no methods available to predict the TNF-α response. Here we have investigated the biomarkers of the gut fungal and bacterial microbiota, which are largely unexplored in paediatric patients, particularly for the fungal microbiota, with the aim to find possible predictors of drug response. Methods The gut microbiota composition of 30 PIBD (25 CD, 2 UC and 3 IBDU) patients at the Children′s Hospital, University of Helsinki receiving the anti-TNF-α drug infliximab (IFX) was studied by MiSeq sequencing targeting the bacterial 16S rRNA gene and fungal ITS region separately from faecal samples collected before the start of treatment and two and six weeks after treatment initiation. The response to IFX was evaluated by a faecal calprotectin value below 100 µg/g at week six after treatment initiation. The fungal MiSeq sequencing data was processed by using the DADA2 pipeline, annotated to the BLAST database and analysed using the package mare. The bacterial MiSeq sequencing data was analysed using mare and annotated to the SILVA database. Results Both the fungal and bacterial microbiota differed significantly between responders compared to non-responders to IFX, further validated by high predictive power (area under curve > 0.8) for therapy response. This difference was characterized by an increase in short-chain fatty acid producing bacteria, such as bacteria in the class Clostridia in the responders at baseline. This was observed as elevated Faecalibacterium and Subdoligranulum genera in particular of responders at baseline. Additionally, Candida was increased while Saccharomyces was decreased in non-responders at the end of the study. Finally, we observed that the interkingdom correlations differed between response groups to IFX. Conclusion Our results strengthen the proposal that the gut microbiota composition of PIBD patients could predict the response to anti-TNF-α treatment in the future.

2018 ◽  
Vol 154 (1) ◽  
pp. S56-S57
Author(s):  
Natalia Danilova ◽  
Rustam Abdulkhakov ◽  
Sayar Abdulkhakov ◽  
Tatyana Grigorieva ◽  
Maria Markelova ◽  
...  

2018 ◽  
Vol 10 (472) ◽  
pp. eaap8914 ◽  
Author(s):  
Arnau Vich Vila ◽  
Floris Imhann ◽  
Valerie Collij ◽  
Soesma A. Jankipersadsing ◽  
Thomas Gurry ◽  
...  

Changes in the gut microbiota have been associated with two of the most common gastrointestinal diseases, inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Here, we performed a case-control analysis using shotgun metagenomic sequencing of stool samples from 1792 individuals with IBD and IBS compared with control individuals in the general population. Despite substantial overlap between the gut microbiome of patients with IBD and IBS compared with control individuals, we were able to use gut microbiota composition differences to distinguish patients with IBD from those with IBS. By combining species-level profiles and strain-level profiles with bacterial growth rates, metabolic functions, antibiotic resistance, and virulence factor analyses, we identified key bacterial species that may be involved in two common gastrointestinal diseases.


Author(s):  
Dikhnah Alshehri ◽  
Omar Saadah ◽  
Mahmoud Mosli ◽  
Sherif Edris ◽  
Rashad Alhindi ◽  
...  

There is a growing body of evidence reinforcing the unique connections between the host microbiome, health and diseases. Due to the extreme importance of the symbiotic relationship between the intestinal microbiome and the host, it is not surprising that any alteration in the gut microbiota would result in various diseases, including inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC). IBD is a chronic, relapsing-remitting condition that is associated with significant morbidity, mortality, compromised quality of life and costly medical care. Dysbiosis is believed to exacerbate the progression of IBD. One of the currently used treatments for IBD are anti-tumor necrosis factor (TNF) drugs, representing a biologic therapy that is reported to have an impact on the gut microbiota composition. The efficacy of anti-TNF agents is hindered by the possibility of non-response, which occurs in 10-20% of treated patients, and secondary loss of response, which occurs in up to 30% of treated patients. This underscores the need for novel therapies and studies that evaluate the role of the gut microbiota in these conditions. The success of any therapeutic strategy for IBD depends on our understanding of the interactions that occur between the gut microbiota and the host. In this review, the health and disease IBD-associated microbiota patterns will be discussed, in addition to the effect of currently used therapies for IBD on the gut microbiota composition, as well as new therapeutic approaches that can be used to overcome the current treatment constraints.


2018 ◽  
Vol 24 (suppl_1) ◽  
pp. S39-S39
Author(s):  
Natalia Danilova ◽  
Rustam Abdulkhakov ◽  
Sayar Abdulkhakov ◽  
Tatyana Grigorieva ◽  
Maria Markelova ◽  
...  

mSystems ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Moran Nunberg ◽  
Nir Werbner ◽  
Hadar Neuman ◽  
Marina Bersudsky ◽  
Alex Braiman ◽  
...  

ABSTRACT Inflammatory bowel diseases (IBD) are a group of chronic inflammatory disorders of the intestine, with as-yet-unclear etiologies, affecting over a million people in the United States alone. With the emergence of microbiome research, numerous studies have shown a connection between shifts in the gut microbiota composition (dysbiosis) and patterns of IBD development. In a previous study, we showed that interleukin 1α (IL-1α) deficiency in IL-1α knockout (KO) mice results in moderate dextran sodium sulfate (DSS)-induced colitis compared to that of wild-type (WT) mice, characterized by reduced inflammation and complete healing, as shown by parameters of weight loss, disease activity index (DAI) score, histology, and cytokine expression. In this study, we tested whether the protective effects of IL-1α deficiency on DSS-induced colitis correlate with changes in the gut microbiota and whether manipulation of the microbiota by cohousing can alter patterns of colon inflammation. We analyzed the gut microbiota composition in both control (WT) and IL-1α KO mice under steady-state homeostasis, during acute DSS-induced colitis, and after recovery using 16S rRNA next-generation sequencing. Additionally, we performed cohousing of both mouse groups and tested the effects on the microbiota and clinical outcomes. We demonstrate that host-derived IL-1α has a clear influence on gut microbiota composition, as well as on severity of DSS-induced acute colon inflammation. Cohousing both successfully changed the gut microbiota composition and increased the disease severity of IL-1α-deficient mice to levels similar to those of WT mice. This study shows a strong and novel correlation between IL-1α expression, microbiota composition, and clinical outcomes of DSS-induced colitis. IMPORTANCE Here, we show a connection between IL-1α expression, microbiota composition, and clinical outcomes of DSS-induced colitis. Specifically, we show that the mild colitis symptoms seen in IL-1α-deficient mice following administration of DSS are correlated with the unique gut microbiota compositions of the mice. However, when these mice are exposed to WT microbiota by cohousing, their gut microbiota composition returns to resemble that of WT mice, and their disease severity increases significantly. As inflammatory bowel diseases are such common diseases, with limited effective treatments to date, there is a great need to better understand the interactions between microbiota composition, the immune system, and colitis. This study shows correlation between microbiota composition and DSS resistance; it may potentially lead to the development of improved probiotics for IBD treatment.


2021 ◽  
Vol 11 (12) ◽  
pp. 1381
Author(s):  
Han-Na Kim ◽  
Jae-Heon Kim ◽  
Yoosoo Chang ◽  
Dongmin Yang ◽  
Hyung-Lae Kim ◽  
...  

Animal studies have shown the interaction between androgens and the gut microbiome directly and indirectly; however, limited evidence from human studies is available. To evaluate the association between prostate-specific antigen (PSA) levels within the normal range, reflective of androgen receptor activity, and the gut microbiota composition, a cross-sectional analysis was performed in 759 Korean men aged between 25 and 78 years with normal PSA levels of ≤4.0 ng/mL. We evaluated the biodiversity of gut microbiota as well as the taxonomic and functional signatures associated with PSA levels using 16S rRNA gene sequencing data. PSA levels within the normal range were categorized into three groups: lowest quartile (G1), interquartile range (G2, reference), and highest quartile (G3). The G3 group had higher microbial richness than the G2 group, although it was dominated by a few bacteria. An increase in Escherichia/Shigella abundance and a reduction in Megamonas abundance in the G3 group were also detected. A U-shaped relationship was observed between the three groups across most analyses, including biodiversity, taxonomic composition, and inferred pathways in the gut microbiota. This study showed different microbiota patterns across PSA levels within the normal range. Further studies are required to elucidate the role of microbiota in regulating PSA levels.


2017 ◽  
Vol 36 (1) ◽  
pp. 56-65 ◽  
Author(s):  
Loris Riccardo Lopetuso ◽  
Valentina Petito ◽  
Cristina Graziani ◽  
Elisa Schiavoni ◽  
Francesco Paroni Sterbini ◽  
...  

Few data exist on differences in gut microbiota composition among principal gastrointestinal (GI) diseases. We evaluated the differences in gut microbiota composition among uncomplicated diverticular disease (DD), irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD) patients. DD, IBS, and IBD patients along with healthy controls (CT) were enrolled in our Italian GI outpatient clinic. Stool samples were collected. Microbiota composition was evaluated through a metagenomic gene-targeted approach. GI pathology represented a continuous spectrum of diseases where IBD displayed one extreme, while CT displayed the other. Among Phyla, Biplot PC2/PC3 and dendogram plot showed major differences in samples from IBS and IBD. DD resembled species CT composition, but not for Bacteroides fragilis. In IBS, Dialister spp. and then Faecalibacterium prausnitzii were the most representative species. Ulcerative colitis showed a reduced concentration of Clostridium difficile and an increase of Bacteroides fragilis. In Crohn's disease, Parabacteroides distasonis was the most represented, while Faecalibacterium prausnitzii and Bacteroides fragilis were significantly reduced. Each disorder has its definite overall microbial signature, which produces a clear differentiation from the others. On the other hand, shared alterations constitute the “core dysbiosis” of GI diseases. The assessment of these microbial markers represents a parameter that may complete the diagnostic assessment.


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