scholarly journals Systemic IgG repertoire as a biomarker for translocating gut microbiota members

2021 ◽  
Author(s):  
Ivan Vujkovic-Cvijin ◽  
Hugh Welles ◽  
Connie W.Y. Ha ◽  
Lutfi Huq ◽  
Shreni Mistry ◽  
...  

While the microbiota has been associated with diseases states, how specific alterations in composition, function, or localization contribute to pathologies remains unclear. The ability of defined microbes to translocate has been linked to diseases including inflammatory bowel disease (IBD) and was shown to promote responses to immune checkpoint therapy. However, scalable and unbiased tools to uncover microbes with enhanced ability to translocate are limited. Herein, we developed an approach to utilize systemic IgG in an unbiased, culture-independent, and high-throughput fashion as a biomarker to identify gut microbiota members that are capable of translocation across the gastrointestinal barrier. We validate these findings in a cohort of human subjects, and highlight a number of microbial taxa against which elevated IgG responses are unique to subjects with IBD including Collinsella, Bifidobacterium, Faecalibacterium, and Blautia spp. Collinsella and Bifidobacterium taxa identified as translocators and targets of immunity in IBD also exhibited heightened bacterial activity and growth rates in Crohn's disease subjects. Our approach may represent a complementary tool to illuminate privileged interactions between host and its microbiota, and may provide an additional lens by which to uncover microbes linked to disease processes.

2016 ◽  
Vol 34 (1-2) ◽  
pp. 64-71 ◽  
Author(s):  
S. Burman ◽  
E.C. Hoedt ◽  
S. Pottenger ◽  
N.-S. Mohd-Najman ◽  
P. Ó Cuív ◽  
...  

While it is now accepted that the gut microbiota contribute to the genotype-environment-lifestyle interactions triggering inflammatory bowel disease (IBD) episodes, efforts to identify the pathogen(s) that cause these diseases have met with limited success. The advent of culture-independent techniques for characterizing the structure and/or function of microbial communities (hereafter referred to as metagenomics) has provided new insights into the events associated with the onset, remission and recurrence of IBD. A large number of observational and/or case-control studies of IBD patients have confirmed substantive changes in gut bacterial profiles (dysbiosis) associated with disease. These types of studies have been augmented by new profiling approaches that support the identification of more ‘colitogenic' bacteria from numerically predominant taxa. Evidence of alterations in lesser abundant taxa such as the methanogenic archaea, to favor types that are more immunogenic, has also been forthcoming. Several recent longitudinal studies of patients with Crohn's disease have produced additional insights, including evidence for the role of ‘anti-inflammatory' microbiota in providing a protective effect and/or promoting remission. In summation, the implications of dysbiosis and restoration of a ‘healthy microbiota' in IBD patients requires definition beyond a taxonomic assessment of the changes in the gut microbiota during disease course. The available evidence does suggest that specific members of the gut microbiota can contribute either pro- or anti-inflammatory effects, and their ecological fitness in the large bowel affects the onset and recurrence of IBD. While metagenomics and related approaches offer the potential to provide novel and important insights into these microbiota and thereby the pathophysiology of IBD, we also need to better understand factors affecting the ecological fitness of these microbes, if new treatment of IBD patients are to be delivered.


2019 ◽  
Author(s):  
Isabel Cornejo-Pareja ◽  
Beatriz Garcia-Munoz ◽  
Eduardo Romero-Perez ◽  
Eduardo Garcia-Fuentes ◽  
S Tapia-Paniagua ◽  
...  

2019 ◽  
Vol 156 (6) ◽  
pp. S-1124
Author(s):  
Clara Caenepeel ◽  
Sara Vieira-Silva ◽  
Jorge F. Vázquez-Castellanos ◽  
Bram Verstockt ◽  
Marc Ferrante ◽  
...  

2017 ◽  
Vol 312 (4) ◽  
pp. G327-G339 ◽  
Author(s):  
Rebecca L. Knoll ◽  
Kristoffer Forslund ◽  
Jens Roat Kultima ◽  
Claudius U. Meyer ◽  
Ulrike Kullmer ◽  
...  

Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn’s disease (CD), six children with ulcerative colitis (UC) and 12 healthy siblings by metagenomic sequencing. In addition, lifetime antibiotic intake was retrospectively determined. Species richness and diversity were significantly reduced in UC patients compared with control [Mann-Whitney U-test false discovery rate (MWU FDR) = 0.011]. In UC, bacteria positively influencing gut homeostasis, e.g., Eubacterium rectale and Faecalibacterium prausnitzii, were significantly reduced in abundance (MWU FDR = 0.05). Known pathobionts like Escherichia coli were enriched in UC patients (MWU FDR = 0.084). Moreover, E. coli abundance correlated positively with that of several virulence genes (SCC > 0.65, FDR < 0.1). A shift toward antibiotic-resistant taxa in both IBD groups distinguished them from controls [MWU Benjamini-Hochberg-Yekutieli procedure (BY) FDR = 0.062 in UC, MWU BY FDR = 0.019 in CD). The collected results confirm a microbial dysbiosis in pediatric UC, and to a lesser extent in CD patients, replicating associations found previously using different methods. Taken together, these observations suggest microbiotal remodeling therapy from family donors, at least for children with UC, as a viable option. NEW & NOTEWORTHY In this sibling study, prior reports of microbial dysbiosis in IBD patients from 16S rRNA sequencing was verified using deep shotgun sequencing and augmented with insights into the abundance of bacterial virulence genes and bacterial antibiotic resistance determinants, seen against the background of data on the specific antibiotic intake of each of the study participants. The observed dysbiosis, which distinguishes patients from siblings, highlights such siblings as potential donors for microbiotal remodeling therapy in IBD.


2021 ◽  
Author(s):  
Mengru Guo ◽  
Xinran Liu ◽  
Yiwei Tan ◽  
Fangyuan Kang ◽  
Xinghua Zhu ◽  
...  

Sucralose is one of the most widely used artificial sweeteners, free of nutrients and calories. It’s approval and uses correlate many of the worldwide epidemiological changes of inflammatory bowel disease...


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