Influences of the colonic microbiome on the mucous gel layer in ulcerative colitis

Lennon, Gráinne; Balfe, Áine; Earley, Helen; Devane, Liam; Lavelle, Aonghus; Winter, Desmond C.; Coffey, J. Calvin; O'Connell, P. R.

doi:10.4161/gmic.28793

Cited by 31 publications

(27 citation statements)

References 100 publications

(121 reference statements)

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“…The levels of mucin in the terminal ileum control tissue were found to be higher than in controls from other tissues. This could in part, be due to a lower level of bacterial microflora in the ileum compared to caecal and colonic tissues that may have contributed to mucin degradation to some extent [ 55 ]. Nevertheless, there was a significant difference between control and infected tissue showing that Blastocystis spp.…”

Section: Resultsmentioning

confidence: 99%

Ex Vivo and In Vivo Mice Models to Study Blastocystis spp. Adhesion, Colonization and Pathology: Closer to Proving Koch's Postulates

et al. 2016

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Blastocystis spp. are widely prevalent extra cellular, non-motile anerobic protists that inhabit the gastrointestinal tract. Although Blastocystis spp. have been associated with gastrointestinal symptoms, irritable bowel syndrome and urticaria, their clinical significance has remained controversial. We established an ex vivo mouse explant model to characterize adhesion in the context of tissue architecture and presence of the mucin layer. Using confocal microscopy with tissue whole mounts and two axenic isolates of Blastocystis spp., subtype 7 with notable differences in adhesion to intestinal epithelial cells (IEC), isolate B (ST7-B) and isolate H (more adhesive, ST7-H), we showed that adhesion is both isolate dependent and tissue trophic. The more adhesive isolate, ST7-H was found to bind preferentially to the colon tissue than caecum and terminal ileum. Both isolates were also found to have mucinolytic effects. We then adapted a DSS colitis mouse model as a susceptible model to study colonization and acute infection by intra-caecal inoculation of trophic Blastocystis spp.cells. We found that the more adhesive isolate ST7-H was also a better colonizer with more mice shedding parasites and for a longer duration than ST7-B. Adhesion and colonization was also associated with increased virulence as ST7-H infected mice showed greater tissue damage than ST7-B. Both the ex vivo and in vivo models used in this study showed that Blastocystis spp. remain luminal and predominantly associated with mucin. This was further confirmed using colonic loop experiments. We were also successfully able to re-infect a second batch of mice with ST7-H isolates obtained from fecal cultures and demonstrated similar histopathological findings and tissue damage thereby coming closer to proving Koch’s postulates for this parasite.

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Section: Resultsmentioning

confidence: 99%

Ex Vivo and In Vivo Mice Models to Study Blastocystis spp. Adhesion, Colonization and Pathology: Closer to Proving Koch's Postulates

et al. 2016

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“…Induction of T regs maintains an anti‐inflammatory milieu and the acidic pH prevents specific pathogens from gaining a foothold. Prebiotics are also speculated to protect the gut epithelium by increasing the mucus layer, elongating the microvilli, increasing numbers of epithelial cells, and by preventing adherence of pathogenic strains to the epithelial cells . Other SCFAs such as propionate appear to induce de novo generation of T regs in the peripheral immune system .…”

Section: Therapeutic Manipulation Of the Gastrointestinal Microbiomementioning

confidence: 99%

“…Prebiotics are also speculated to protect the gut epithelium by increasing the mucus layer, elongating the microvilli, increasing numbers of epithelial cells, and by preventing adherence of pathogenic strains to the epithelial cells. 140,141 Other SCFAs such as propionate appear to induce de novo generation of T regs in the peripheral immune system. 142 A newly published study in mice revealed that when deprived of fiber, commensal bacteria will degrade the protective mucosal mucus layer, permitting invasion by commensals and pathogens alike.…”

Section: Prebioticsmentioning

confidence: 99%

The Gastrointestinal Microbiome: A Review

Barko

McMichael

Swanson

et al. 2017

Veterinary Internal Medicne

533

382

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The gastrointestinal microbiome is a diverse consortium of bacteria, archaea, fungi, protozoa, and viruses that inhabit the gut of all mammals. Studies in humans and other mammals have implicated the microbiome in a range of physiologic processes that are vital to host health including energy homeostasis, metabolism, gut epithelial health, immunologic activity, and neurobehavioral development. The microbial genome confers metabolic capabilities exceeding those of the host organism alone, making the gut microbiome an active participant in host physiology. Recent advances in DNA sequencing technology and computational biology have revolutionized the field of microbiomics, permitting mechanistic evaluation of the relationships between an animal and its microbial symbionts. Changes in the gastrointestinal microbiome are associated with diseases in humans and animals including inflammatory bowel disease, asthma, obesity, metabolic syndrome, cardiovascular disease, immune‐mediated conditions, and neurodevelopmental conditions such as autism spectrum disorder. While there remains a paucity of data regarding the intestinal microbiome in small animals, recent studies have helped to characterize its role in host animal health and associated disease states. This review is intended to familiarize small animal veterinarians with recent advances in the field of microbiomics and to prime them for a future in which diagnostic tests and therapies will incorporate these developments into clinical practice.

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“…In ulcerative colitis (UC), changes occur in the MGL that may alter its protective capacity [ 8 – 10 ]. These include physical changes in the mucus barrier [ 11 ], altered mucin gene expression [ 12 ] and biochemical changes affecting the mucins [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

A Preliminary Study Examining the Binding Capacity of Akkermansia muciniphila and Desulfovibrio spp., to Colonic Mucin in Health and Ulcerative Colitis

et al. 2015

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Background Akkermansia muciniphila and Desulfovibrio spp. are commensal microbes colonising the mucus gel layer of the colon. Both species have the capacity to utilise colonic mucin as a substrate. A. muciniphila degrades colonic mucin, while Desulfovibrio spp. metabolise the sulfate moiety of sulfated mucins. Altered abundances of these microorganisms have been reported in ulcerative colitis (UC). However their capacity to bind to human colonic mucin, and whether this binding capacity is affected by changes in mucin associated with UC, remain to be defined.MethodsMucin was isolated from resected colon from control patients undergoing resection for colonic cancer (n = 7) and patients undergoing resection for UC (n = 5). Isolated mucin was purified and printed onto mucin microarrays. Binding of reference strains and three clinical isolates of A. muciniphila and Desulfovibrio spp. to purified mucin was investigated.ResultsBoth A. muciniphila and Desulfovibro spp. bound to mucin. The reference strain and all clinical isolates of A. muciniphila showed increased binding capacity for UC mucin (p < .005). The Desulfovibrio reference strain showed increased affinity for UC mucin. The mucin binding profiles of clinical isolates of Desulfovibrio spp. were specific to each isolate. Two isolates showed no difference in binding. One UC isolate bound with increased affinity to UC mucin (p < .005).ConclusionThese preliminary data suggest that differences exist in the mucin binding capacity of isolates of A. muciniphila and Desulfovibrio spp. This study highlights the mucin microarray platform as a means of studying the ability of bacteria to interact with colonic mucin in health and disease.

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Influences of the colonic microbiome on the mucous gel layer in ulcerative colitis

Cited by 31 publications

References 100 publications

Ex Vivo and In Vivo Mice Models to Study Blastocystis spp. Adhesion, Colonization and Pathology: Closer to Proving Koch's Postulates

Ex Vivo and In Vivo Mice Models to Study Blastocystis spp. Adhesion, Colonization and Pathology: Closer to Proving Koch's Postulates

The Gastrointestinal Microbiome: A Review

A Preliminary Study Examining the Binding Capacity of Akkermansia muciniphila and Desulfovibrio spp., to Colonic Mucin in Health and Ulcerative Colitis

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