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PubMed abstracts for UC pathobiont/mucus-layer digest 009

Saved 38 records from NCBI E-utilities on 2026-06-18.

PMID 23426893 — Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis.

  • Journal: Gut (2014)
  • DOI: 10.1136/gutjnl-2012-303207
  • URL: https://pubmed.ncbi.nlm.nih.gov/23426893/
  • Authors: Johansson ME, Gustafsson JK, Holmén-Larsson J, Jabbar KS, Xia L, Xu H, Ghishan FK, Carvalho FA

The inner mucus layer in mouse colon normally separates bacteria from the epithelium. Do humans have a similar inner mucus layer and are defects in this mucus layer a common denominator for spontaneous colitis in mice models and ulcerative colitis (UC)? The colon mucus layer from mice deficient in Muc2 mucin, Core 1 O-glycans, Tlr5, interleukin 10 (IL-10) and Slc9a3 (Nhe3) together with that from dextran sodium sulfate-treated mice was immunostained for Muc2, and bacterial localisation in the mucus was analysed. All murine colitis models revealed bacteria in contact with the epithelium. Additional analysis of the less inflamed IL-10(-/-) mice revealed a thicker mucus layer than wild-type, but the properties were different, as the inner mucus layer could be penetrated both by bacteria in vivo and by fluorescent beads the size of bacteria ex vivo. Clear separation between bacteria or fluorescent beads and the epithelium mediated by the inner mucus layer was also evident in normal human sigmoid colon biopsy samples. In contrast, mucus on colon biopsy specimens from patients with UC with acute inflammation was highly penetrable. Most patients with UC in remission had an impenetrable mucus layer similar to that of controls. Normal human sigmoid colon has an inner mucus layer that is impenetrable to bacteria. The colon mucus in animal models that spontaneously develop colitis and in patients with active UC allows bacteria to penetrate and reach the epithelium. Thus colon mucus properties can be modulated, and this suggests a novel model of UC pathophysiology.

PMID 18806221 — The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria.

  • Journal: Proceedings of the National Academy of Sciences of the United States of America (2008)
  • DOI: 10.1073/pnas.0803124105
  • URL: https://pubmed.ncbi.nlm.nih.gov/18806221/
  • Authors: Johansson ME, Phillipson M, Petersson J, Velcich A, Holm L, Hansson GC

We normally live in symbiosis with approximately 10(13) bacteria present in the colon. Among the several mechanisms maintaining the bacteria/host balance, there is limited understanding of the structure, function, and properties of intestinal mucus. We now demonstrate that the mouse colonic mucus consists of two layers extending 150 mum above the epithelial cells. Proteomics revealed that both of these layers have similar protein composition, with the large gel-forming mucin Muc2 as the major structural component. The inner layer is densely packed, firmly attached to the epithelium, and devoid of bacteria. In contrast, the outer layer is movable, has an expanded volume due to proteolytic cleavages of the Muc2 mucin, and is colonized by bacteria. Muc2(-/-) mice have bacteria in direct contact with the epithelial cells and far down in the crypts, explaining the inflammation and cancer development observed in these animals. These findings show that the Muc2 mucin can build a mucus barrier that separates bacteria from the colon epithelia and suggest that defects in this mucus can cause colon inflammation.

PMID 31209051 — Synaptic crosstalk conferred by a zone of differentially regulated Ca2+ signaling in the dendritic shaft adjoining a potentiated spine.

  • Journal: Proceedings of the National Academy of Sciences of the United States of America (2019)
  • DOI: 10.1073/pnas.1902461116
  • URL: https://pubmed.ncbi.nlm.nih.gov/31209051/
  • Authors: Dittmer PJ, Dell’Acqua ML, Sather WA

Patterns of postsynaptic activity that induce long-term potentiation of fast excitatory transmission at glutamatergic synapses between hippocampal neurons cause enlargement of the dendritic spine and promote growth in spine endoplasmic reticulum (ER) content. Such postsynaptic activity patterns also impact Ca2+ signaling in the adjoining dendritic shaft, in a zone centered on the spine-shaft junction and extending ∼10-20 µm in either direction along the shaft. Comparing this specialized zone in the shaft with the dendrite in general, plasticity-inducing stimulation of a single spine causes more profound depletion of Ca2+ stores in the ER, a greater degree of interaction between stromal interaction molecule 1 (STIM1) and L-type Ca2+ channels, and thus stronger STIM1 inhibition of these channels. Here we show that the length of this zone along the dendritic axis can be approximately doubled through the neuromodulatory action of β-adrenergic receptors (βARs). The mechanism of βAR enlargement of the zone arises from protein kinase A-mediated enhancement of L-type Ca2+ current, which in turn lowers [Ca2+]ER through ryanodine receptor-dependent Ca2+-induced Ca2+ release and activates STIM1 feedback inhibition of L-type Ca2+ channels. An important function of this dendritic zone is to support crosstalk between spines along its length such that spines neighboring a strongly stimulated spine are enabled to undergo structural plasticity in response to stimulation that would otherwise be subthreshold for spine structural plasticity. This form of crosstalk requires L-type Ca2+ channel current to activate STIM1, and βAR activity extends the range along the shaft over which such spine-to-spine communication can occur.

PMID 40783488 — Periodontitis-associated Fusobacterium nucleatum promotes ulcerative colitis by ferroptosis-mediated gut barrier disruption.

Periodontitis and ulcerative colitis (UC) are inflammatory diseases linked through the “gum-gut” axis. Fusobacterium nucleatum, an important periodontitis-associated pathobiont and gastrointestinal opportunist, may mediate their comorbidity. This study investigated the role of F. nucleatum in UC using dextran sulfate sodium-induced UC and F. nucleatum-induced periodontitis models. F. nucleatum exacerbated inflammatory alveolar bone loss and intestinal barrier dysfunction, accelerating UC severity. Integrated 16S rRNA gene sequence and LC-MS metabolomics revealed ferroptosis activation, characterized by elevated Fe2+ and malondialdehyde, glutathione depletion, dysregulated GPX4, FTH1, and ACSL4 expression, reduced mitochondrial membrane potential, and reactive oxygen species aggregation in the mouse colon and colonic epithelial cell CCD841. Administration of ferroptosis inhibitor Ferrostatin-1 attenuated UC by restoring intestinal permeability, preserving mucin layers, and enhancing tight junction proteins ZO-1 and CLDN-1. These findings establish F. nucleatum as a key mediator of periodontitis-UC comorbidity through ferroptosis-mediated gut barrier disruption, providing mechanistic insights into microbial-driven inflammatory cross-talk.

PMID 41264718 — A bacterial toxin disarms gut defenses against inflammation.

Macrophage-toxic bacteria from patients with ulcerative colitis worsen gut inflammation in mice.

PMID 41080054 — Advancements in understanding the relationship between Akkermansia muciniphila and the development of ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by severe intestinal barrier dysfunction and immune dysregulation in patients, with limited clinical treatment options. Recent research highlights the important role of the gut bacterium Akkermansia muciniphila (AKK) in both the development and management of UC. AKK supports the integrity of the intestinal barrier by metabolizing mucins, enhances the production of tight junction proteins (Occludin-1/ZO-1), and influences immune responses by shifting macrophage polarization from M1 to M2, suppressing pro-inflammatory cytokines (IL-1β、IL-6、MCP-1), and activating anti-inflammatory pathways (SCFAs-SLC52A2/FFAR2、AhR). Clinical data indicate that the abundance of AKK in the intestines of patients with UC is significantly reduced, and this decrease is positively correlated with disease activity and relapse rates. Animal studies have demonstrated that adding AKK can restore the thickness of the mucus layer, lower inflammation scores, and improve the composition of gut microbiota. Importantly, the probiotic effects of AKK vary by strain; for instance, strain FSDLZ36M5 notably reduces colitis symptoms, while FSDLZ20M4 may worsen inflammation. These findings suggest that AKK or its metabolites, such as short-chain fatty acid(SCFAs), hold promise as therapeutic targets for the microbiota in patients with UC.Nonetheless, additional research on strain selection and clinical application is essential to refine treatment strategies. This article will review the correlation between the pathogenesis of AKK and UC, and explore the potential application value of AKK as a probiotic in children with UC, providing new insights for the prevention and treatment in patients with UC.

PMID 41264716 — An Aeromonas variant that produces aerolysin promotes susceptibility to ulcerative colitis.

Ulcerative colitis (UC) is a severe inflammatory bowel disease affecting millions of people worldwide, but the factors driving the condition are poorly understood. In tissue samples from individuals with UC, we found that macrophages were depleted from areas of the colon that did not yet exhibit overt epithelial inflammation. We hypothesized that toxins produced by bacteria could impair macrophages and that this could promote wider inflammation. We isolated a variant of Aeromonas genus from stool samples from UC patients, which we termed macrophage-toxic bacteria (MTB), because aerolysin secreted by MTB caused macrophage death. MTB colonized mice under pathogenic conditions and triggered colitis. Antibodies against aerolysin alleviated colitis induced by Aeromonas in mice. In a cohort, UC patients more frequently tested positive for Aeromonas than healthy controls did.

PMID 40260115 — Oral Fusobacterium nucleatum exacerbates ulcerative colitis via the oral-gut axis: mechanisms and therapeutic implications.

Fusobacterium nucleatum (F. nucleatum) is an anaerobic bacterium known for its association with periodontal disease and oral infections. It has been implicated in the development of gastrointestinal diseases such as inflammatory bowel disease and colorectal cancer. Ulcerative colitis (UC), which is characterized by chronic inflammation of the colon, is a condition of unknown etiology with a rising incidence rate, significantly affecting the quality of life for patients. The increased intestinal permeability during UC may facilitate the adherence or invasion of F. nucleatum into the damaged intestinal barrier, leading to exacerbated inflammation. This article introduces the concept of the oral-gut axis, reviewing existing literature to analyze the role of F. nucleatum in the pathogenesis of UC and exploring its potential pathogenic mechanisms. It also summarizes the latest advances in treating patients with UC who have F. nucleatum and looks forward to prospective therapeutic strategies and the translational prospects of F. nucleatum within the oral-gut axis. F. nucleatum may be a key player in the pathogenesis of UC, likely due to its invasiveness during periods of increased intestinal permeability. The paper also discusses innovative approaches for the prevention and management of UC exacerbated by F. nucleatum, paving the way for more effective treatment of UC. The review offers new insights into the complex relationship between the oral microbiome and intestinal diseases, enhancing our understanding of their dynamic interactions. There is a paucity of literature on therapeutic approaches, indicating a need for further clinical research.

PMID 38376725 — Antibiotics for inflammatory bowel disease: Current status.

  • Journal: Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology (2024)
  • DOI: 10.1007/s12664-024-01537-x
  • URL: https://pubmed.ncbi.nlm.nih.gov/38376725/
  • Authors: Jha DK, Mishra S, Dutta U, Sharma V

There is abundant literature reporting about the use of antibiotics in inflammatory bowel disease (IBD), but their role in the management of IBD is not entirely clear. Diverse infectious organisms have been implicated in the pathogenesis of Crohn’s disease. Also, infections are believed to be a trigger for flares of ulcerative colitis. The benefit of the routine use of antibiotics in IBD is equivocal. However, there are certain situations, where antibiotics have a clear role and evidence of benefit: perianal fistula, intra-abdominal abscesses in Crohn’s disease, acute pouchitis and infection-related flares. However, there is a lack of supportive evidence for the routine use of antibiotics in all disease-related flares. Evidence indicates a lack of benefit of intravenous antibiotics in acute severe ulcerative colitis and only limited benefit in active ulcerative colitis. Limited evidence suggests the role of a combination of oral antibiotics in pediatric ulcerative colitis. Certain targeted antibiotic regimens have been used in IBD. In ulcerative colitis, limited evidence suggests the benefit of the use of an antibiotic cocktail directed against Fusobacterium varium. Therapy directed against Escherichia coli does not seem to have a benefit in inflammatory Crohn’s disease. In Crohn’s disease, antimycobacterial therapy may result in symptomatic improvement but no durable benefit. Antitubercular therapy (ATT), on the contrary, may result in fibrotic transformation, suggesting a need to avoid misdiagnosis and limit the duration of ATT in Crohn’s disease. This review assesses the published literature with respect to antibiotic use and provides guidance to clinicians in appropriate antibiotic use in various situations in the setting of IBD.

PMID 38825783 — Archaea influence composition of endoscopically visible ileocolonic biofilms.

  • Journal: Gut microbes (2024)
  • DOI: 10.1080/19490976.2024.2359500
  • URL: https://pubmed.ncbi.nlm.nih.gov/38825783/
  • Authors: Orgler E, Baumgartner M, Duller S, Kumptisch C, Hausmann B, Moser D, Khare V, Lang M

The gut microbiota has been implicated as a driver of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Recently we described, mucosal biofilms, signifying alterations in microbiota composition and bile acid (BA) metabolism in IBS and ulcerative colitis (UC). Luminal oxygen concentration is a key factor in the gastrointestinal (GI) ecosystem and might be increased in IBS and UC. Here we analyzed the role of archaea as a marker for hypoxia in mucosal biofilms and GI homeostasis. The effects of archaea on microbiome composition and metabolites were analyzed via amplicon sequencing and untargeted metabolomics in 154 stool samples of IBS-, UC-patients and controls. Mucosal biofilms were collected in a subset of patients and examined for their bacterial, fungal and archaeal composition. Absence of archaea, specifically Methanobrevibacter, correlated with disrupted GI homeostasis including decreased microbial diversity, overgrowth of facultative anaerobes and conjugated secondary BA. IBS-D/-M was associated with absence of archaea. Presence of Methanobrevibacter correlated with Oscillospiraceae and epithelial short chain fatty acid metabolism and decreased levels of Ruminococcus gnavus. Absence of fecal Methanobrevibacter may indicate a less hypoxic GI environment, reduced fatty acid oxidation, overgrowth of facultative anaerobes and disrupted BA deconjugation. Archaea and Ruminococcus gnavus could distinguish distinct subtypes of mucosal biofilms. Further research on the connection between archaea, mucosal biofilms and small intestinal bacterial overgrowth should be performed.

PMID 39118149 — Lower fecal microbiota transplantation ameliorates ulcerative colitis by eliminating oral-derived Fusobacterium nucleatum and virulence factor.

Recently, the oral oncobacterium Fusobacterium nucleatum (F. nucleatum), has been linked with ulcerative colitis (UC). Here, we aim to investigate whether Fecal Microbiota Transplantation (FMT) can alleviate UC by restoring gut microbiota and eliminating oral-derived F. nucleatum and virulence factor fadA. C57BL/6J mice were randomly divided into a healthy control group (HC), Dextran Sulfate Sodium group (DSS), oral inoculation group (OR), upper FMT group (UFMT), and lower FMT group (LFMT). Disease activity index, body weight, survival rate, and histopathological scores were used to measure the severity of colitis. The function of the intestinal mucosal barrier was evaluated by performing immunohistochemical staining of the tight junction protein Occludin. Real-time PCR was used to assess the relative abundance of the nusG gene and the virulence gene fadA. Cytokine levels were detected by ELISA. Full-length sequencing of 16S rRNA was used to analyze the changes and composition of gut microbiota. Oral incubation of F. nucleatum further exacerbated the severity of colitis and gut dysbiosis. Peptostreptococcaceae, Enterococcaceae, and Escherichia coli were significantly enriched in OR mice. However, LFMT mice showed an obvious decrease in disease activity and were more effective in restoring gut microbiota and eliminating F. nucleatum than UFMT mice. Bacteroidota, Lachnospiraceae, and Prevotellaceae were mainly enriched bacteria in LFMT mice. In addition, Genera such as Lactobacillus, Allobaculum, and Bacteroidales were found negative correlation with TNF-α, IL-1β, and IL-6. Genera like Romboutsia, Escherichia Shigella, Enterococcus, and Clostridium were found positively correlated with TNF-α, IL-1β, and IL-6. Oral incubation of F. nucleatum further exacerbates the severity and dysbiosis in DSS-induced colitis mice. Besides, lower tract FMT can ameliorate colitis by restoring the gut microbiota diversity and eliminating F. nucleatum and virulence factor fadA.

PMID 39221673 — Oral inoculation of Fusobacterium nucleatum exacerbates ulcerative colitis via the secretion of virulence adhesin FadA.

Fusobacterium nucleatum (F. nucleatum), an anaerobic resident of the oral cavity, is increasingly recognized as a contributing factor to ulcerative colitis (UC). The adhesive properties of F. nucleatum are mediated by its key virulence protein, FadA adhesin. However, further investigations are needed to understand the pathogenic mechanisms of this oral pathogen in UC. The present study aimed to explore the role of the FadA adhesin in the colonization and invasion of oral F. nucleatum in dextran sulphate sodium (DSS)-induced colitis mice via molecular techniques. In this study, we found that oral inoculation of F. nucleatum strain carrying the FadA adhesin further exacerbated DSS-induced colitis, leading to elevated alveolar bone loss, disease severity, and mortality. Additionally, CDH1 gene knockout mice treated with DSS presented increases in body weight and alveolar bone density, as well as a reduction in disease severity. Furthermore, FadA adhesin adhered to its mucosal receptor E-cadherin, leading to the phosphorylation of β-catenin and the degradation of IκBα, the activation of the NF-κB signalling pathway and the upregulation of downstream cytokines. In conclusion, this research revealed that oral inoculation with F. nucleatum facilitates experimental colitis via the secretion of the virulence adhesin FadA. Targeting the oral pathogen F. nucleatum and its virulence factor FadA may represent a promising therapeutic approach for a portion of UC patients.

PMID 38138026 — Evaluation of Bacterial and Fungal Biomarkers for Differentiation and Prognosis of Patients with Inflammatory Bowel Disease.

This study aimed to evaluate bacterial and fungal biomarkers to differentiate patients with inflammatory bowel disease (IBD), predict the IBD prognosis, and determine the relationship of these biomarkers with IBD pathogenesis. The composition and function of bacteria and fungi in stool from 100 IBD patients and 97 controls were profiled using next-generation sequencing. We evaluated the cumulative risk of relapse according to bacterial and fungal enterotypes. The microbiome and mycobiome alpha diversity in IBD patients were significantly lower and higher than in the controls, respectively; the micro/mycobiome beta diversity differed significantly between IBD patients and the controls. Ruminococcus gnavus, Cyberlindnera jadinii, and Candida tropicalis increased in IBD patients. Combining functional and species analyses revealed that lower sugar import and higher modified polysaccharide production were associated with IBD pathogenesis. Tricarboxylic acid cycling consuming acetyl CoA was higher in IBD patients than the controls, leading to lower short-chain fatty acid (SCFA) fermentation. Bacterial and fungal enterotypes were not associated with IBD relapse. We found differences in bacterial and fungal species between IBD patients and controls. A working model for the role of gut bacteria in IBD pathogenesis is proposed, wherein bacterial species increase modified N-glycan production and decrease SCFA fermentation.

PMID 35237276 — Human Fecal Microbiota Transplantation Reduces the Susceptibility to Dextran Sulfate Sodium-Induced Germ-Free Mouse Colitis.

In clinical practice, fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease (IBD), and has shown certain effects. However, the selection of FMT donors and the mechanism underlying the effect of FMT intervention in IBD require further exploration. In this study, dextran sodium sulfate (DSS)-induced colitis mice were used to determine the differences in the protection of colitis symptoms, inflammation, and intestinal barrier, by FMT from two donors. Intriguingly, pre-administration of healthy bacterial fluid significantly relieved the symptoms of colitis compared to the ulcerative colitis (UC) bacteria. In addition, healthy donor (HD) bacteria significantly reduced the levels of inflammatory markers Myeloperoxidase (MPO) and Eosinophil peroxidase (EPO), and various pro-inflammatory factors, in colitis mice, and increased the secretion of the anti-inflammatory factor IL-10. Metagenomic sequencing indicated higher species diversity and higher abundance of anti-inflammatory bacteria in the HD intervention group, including Alistipes putredinis, Akkermansia muciniphila, Bifidobacterium adolescentis, short-chain fatty acids (SCFAs)-producing bacterium Christensenella minuta, and secondary bile acids (SBAs)-producing bacterium Clostridium leptum. In the UC intervention group, the SCFA-producing bacterium Bacteroides stercoris, IBD-related bacterium Ruminococcus gnavus, Enterococcus faecalis, and the conditional pathogen Bacteroides caccae, were more abundant. Metabolomics analysis showed that the two types of FMT significantly modulated the metabolism of DSS-induced mice. Moreover, compared with the UC intervention group, indoleacetic acid and unsaturated fatty acids (DHA, DPA, and EPA) with anti-inflammatory effects were significantly enriched in the HD intervention group. In summary, these results indicate that FMT can alleviate the symptoms of colitis, and the effect of HD intervention is better than that of UC intervention. This study offers new insights into the mechanisms of FMT clinical intervention in IBD.

PMID 35705557 — Mitochondrial complex I dysfunction alters the balance of soluble and membrane-bound TNF during chronic experimental colitis.

  • Journal: Scientific reports (2022)
  • DOI: 10.1038/s41598-022-13480-y
  • URL: https://pubmed.ncbi.nlm.nih.gov/35705557/
  • Authors: Peña-Cearra A, Pascual-Itoiz MA, Lavín JL, Fuertes M, Martín-Ruiz I, Castelo J, Palacios A, Barriales D

Inflammatory bowel disease (IBD) is a complex, chronic, relapsing and heterogeneous disease induced by environmental, genomic, microbial and immunological factors. MCJ is a mitochondrial protein that regulates the metabolic status of macrophages and their response to translocated bacteria. Previously, an acute murine model of DSS-induced colitis showed increased disease severity due to MCJ deficiency. Unexpectedly, we now show that MCJ-deficient mice have augmented tumor necrosis factor α converting enzyme (TACE) activity in the context of chronic inflammation. This adaptative change likely affects the balance between soluble and transmembrane TNF and supports the association of the soluble form and a milder phenotype. Interestingly, the general shifts in microbial composition previously observed during acute inflammation were absent in the chronic model of inflammation in MCJ-deficient mice. However, the lack of the mitochondrial protein resulted in increased alpha diversity and the reduction in critical microbial members associated with inflammation, such as Ruminococcus gnavus, which could be associated with TACE activity. These results provide evidence of the dynamic metabolic adaptation of the colon tissue to chronic inflammatory changes mediated by the control of mitochondrial function.

PMID 33972416 — Capsular polysaccharide correlates with immune response to the human gut microbe Ruminococcus gnavus.

  • Journal: Proceedings of the National Academy of Sciences of the United States of America (2021)
  • DOI: 10.1073/pnas.2007595118
  • URL: https://pubmed.ncbi.nlm.nih.gov/33972416/
  • Authors: Henke MT, Brown EM, Cassilly CD, Vlamakis H, Xavier RJ, Clardy J

Active inflammatory bowel disease (IBD) often coincides with increases of Ruminococcus gnavus, a gut microbe found in nearly everyone. It was not known how, or if, this correlation contributed to disease. We investigated clinical isolates of R. gnavus to identify molecular mechanisms that would link R. gnavus to inflammation. Here, we show that only some isolates of R. gnavus produce a capsular polysaccharide that promotes a tolerogenic immune response, whereas isolates lacking functional capsule biosynthetic genes elicit robust proinflammatory responses in vitro. Germ-free mice colonized with an isolate of R. gnavus lacking a capsule show increased measures of gut inflammation compared to those colonized with an encapsulated isolate in vivo. These observations in the context of our earlier identification of an inflammatory cell-wall polysaccharide reveal how some strains of R. gnavus could drive the inflammatory responses that characterize IBD.

PMID 34519941 — Mucolytic bacteria: prevalence in various pathological diseases.

All mucins are highly glycosylated and a key constituent of the mucus layer that is vigilant against pathogens in many organ systems of animals and humans. The viscous layer is organized in bilayers, i.e., an outer layer that is loosely arranged, variable in thickness, home to the commensal microbiota that grows in the complex environment, and an innermost layer that is stratified, non-aspirated, firmly adherent to the epithelial cells and devoid of any microorganisms. The O-glycosylation moiety represents the site of adhesion for pathogens and due to the increase of motility, mucolytic activity, and upregulation of virulence factors, some microorganisms can circumvent the component of the mucus layer and cause disruption in organ homeostasis. A dysbiotic microbiome, defective mucus barrier, and altered immune response often result in various diseases. In this review, paramount emphasis is given to the role played by the bacterial species directly or indirectly involved in mucin degradation, alteration in mucus secretion or its composition or mucin gene expression, which instigates many diseases in the digestive, respiratory, and other organ systems. A systematic view can help better understand the etiology of some complex disorders such as cystic fibrosis, ulcerative colitis and expand our knowledge about mucin degraders to develop new therapeutic approaches to correct ill effects caused by these mucin-dwelling pathogens.

PMID 33318867 — Possible synergy effect of hydrogen sulfide and acetate produced by sulfate-reducing bacteria on inflammatory bowel disease development.

Increased numbers of sulfate-reducing bacteria (SRB) are often found in the feces of people and animals with inflammatory bowel disease. The final products of their metabolism are hydrogen sulfide and acetate, which are produced during dissimilatory sulfate reduction process. The aim of the study was to monitor processes concerning sulfate reduction microbial metabolisms, including: the main microbial genera monitoring and their hydrogen sulfide production in the intestines of healthy and not healthy individuals, phylogenetic analysis of SRB isolates, cluster analysis of SRB physiological and biochemical parameters, SRB growth kinetic parameters calculation, same as the application of the two-factor dispersion analysis for finding relationship between SRB biomass accumulation, temperature and pH. Feces samples from healthy people and patients with colitis were used for isolation of sulfate-reducing microbial communities. Microbiological, biochemical, biophysical, molecular biology methods, and statistical processing of the results have been used for making an evaluation of gained results. Two dominant SRB morphotypes differed in colony size and quantitative ratio in the feces of healthy and colitis patients were observed and identified. In the feces of healthy people, 93% of SRB of morphotype I prevailed (Desulfovibrio) while morphotype II made only 7% (Desulfomicrobium); in the feces of patients with colitis, the ratio of these morphotypes was 99:1, respectively. Hydrogen sulfide concentrations are also higher in the feces of people with colitis and certain synergy effects exist among acetate produced by SRB. The study results brought important findings concerning colony environments with developed colitis and these findings can lead to the development of possible risk indicators of ulcerative colitis prevalence.

PMID 30775453 — Analysis of pH Dose-dependent Growth of Sulfate-reducing Bacteria.

Lower intraluminal colonic pH is an indication for the development of inflammatory bowel disease including active ulcerative colitis. Involvement of intestinal sulfate-reducing bacteria in decreasing bowel pH by the production of H2S and acetate as well as their sensitivity has never been reported before. The study of the relative pH and survival of Desulfovibrio piger Vib-7 by monitoring sulfate reduction parameters was the aim of this work. Monitoring was done through the measurement of bacterial growth (biomass), dissimilatory sulfate reduction parameters: sulfate consumption, lactate oxidation, hydrogen sulfide and acetate production. According to our results, we observed that lower pH (<5) significantly inhibited D. piger Vib-7 growth. This inhibition was also noticed when alkaline media (>9 pH) was used, though the reduction was not at the rate as in media with pH of 4. The research indicates that the growth of D. piger Vib-7 is inhibited at pH of 4 which is not as low as the pH found in people with severely developed inflammatory bowel diseases such as ulcerative colitis. Certainly the interaction (synergistic effect) between both hydrogen sulfide and acetate accumulation can also play an important etiological role in the development of bowel inflammation in humans and animals.

PMID 31117112 — Mucosa-Associated Microbiota in Ileoanal Pouches May Contribute to Clinical Symptoms, Particularly Stool Frequency, Independent of Endoscopic Disease Activity.

  • Journal: Clinical and translational gastroenterology (2019)
  • DOI: 10.14309/ctg.0000000000000038
  • URL: https://pubmed.ncbi.nlm.nih.gov/31117112/
  • Authors: Turpin W, Kelly O, Borowski K, Boland K, Tyler A, Cohen Z, Croitoru K, Silverberg MS

Pouchitis is a common complication after ileal pouch-anal anastomosis (IPAA). However, there is a poor correlation between symptoms and endoscopic appearance of the pouch, and many patients can have debilitating symptoms in the absence of overt inflammation. It is unknown whether these clinical symptoms are independently associated with the microbiota. The objective of this work was to examine whether the individual clinical components of the pouch activity scoring systems are associated with specific microbiota. Pouch biopsies from 233 patients (50% male, 100% IPAA/ulcerative colitis) post-IPAA were included. Clinical phenotyping was performed, and patients were classified using both clinical and endoscopic components of the Pouch Activity Scale. Scoring for symptoms examined 24-hour stool frequency, urgency, incontinence, and rectal bleeding as described by the Pouchitis Disease Activity Index Score. In the absence of inflammation, an increase in stool frequency reported over 24 hours was associated with a decrease in Bacteroidetes relative abundance, and this was the strongest association found. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis in inflamed groups showed that an increase in 24-hour stool frequency was associated with an increase in biofilm formation. These findings indicate that in patients with IPAA, the composition of mucosa-associated microbiota of the pouch may contribute to clinical symptoms, particularly stool frequency, independent of endoscopic disease activity.

PMID 30707247 — Toxicity of hydrogen sulfide toward sulfate-reducing bacteria Desulfovibrio piger Vib-7.

Sulfate-reducing bacteria (SRB) belonging to the intestinal microbiota are the main producers of hydrogen sulfide and their increasing amount due to the accumulation of this compound in the bowel are involved in the initiation and maintenance of inflammatory bowel disease. The purpose of this experiment is to study the relative toxicity of hydrogen sulfide and survival of Desulfovibrio piger Vib-7 through monitoring: sulfate reduction parameters (sulfate consumption, hydrogen sulfide production, lactate consumption and acetate production) and kinetic parameters of these processes. The research is highlighting the survival of intestinal SRB, D. piger Vib-7 under the influence of different hydrogen sulfide concentrations (1-7 mM). The highest toxicity of H2S was measured in the presence of concentrations higher than 6 mM, where growing was stopped, though metabolic activities were not 100% inhibited. These findings are confirmed by cross correlation and principal component analysis that clearly supported the above mentioned results. The kinetic parameters of bacterial growth and sulfate reduction were inhibited proportionally with increasing H2S concentration. The presence of 5 mM H2S resulted in two times longer lag phase and generation time was eight times longer. Maximum rate of growth and hydrogen production was stopped under 4 mM, emphasizing the H2S toxicity concentrations to be < 4 mM, even for sulfide producing bacteria such as Desulfovibrio. The results are confirming H2S concentrations toxicity toward Desulfovibrio, especially the study novelty should be emphasized where it was found that the exact H2S limits (> 4 mM) toward this bacterial strain inhabiting humans and animals intestine.

PMID 30191181 — Metabolic Activity of Sulfate-Reducing Bacteria from Rodents with Colitis.

Sulfate-reducing bacteria (SRB) are anaerobic microorganisms, which use sulfate as an electron acceptor in the process of dissimilatory sulfate reduction. The final metabolic product of these anaerobic microorganisms is hydrogen sulfide, which is known as toxic and can lead to damage to epithelial cells of the large intestine at high concentrations. Different genera of SRB are detected in the large intestine of healthy human and animals, and with diseases like Crohn’s disease and ulcerative colitis. SRB isolated from rodents with ulcerative colitis have produced 1.14 (mice) and 1.03 (rats) times more sulfide ions than healthy rodents. The species of Desulfovibrio genus are the most widespread among all SRB in the intestine. The object of our research was to observe and compare the difference of production of sulfide and reduction of sulfate in intestinal SRB isolated from healthy rodents and rodents with ulcerative colitis.

PMID 27271818 — The immunology of the vermiform appendix: a review of the literature.

This literature review assesses the current knowledge about the immunological aspects of the vermiform appendix in health and disease. An essential part of its immunological function is the interaction with the intestinal bacteria, a trait shown to be preserved during its evolution. The existence of the appendiceal biofilm in particular has proved to have a beneficial effect for the entire gut. In assessing the influence of acute appendicitis and the importance of a normally functioning gut flora, however, multiple immunological aspects point towards the appendix as a priming site for ulcerative colitis. Describing the immunological and microbiotical changes in the appendix during acute and chronic inflammation of the appendix, this review suggests that this association becomes increasingly plausible. Sustained by the distinct composition of cells, molecules and microbiota, as well as by the ever more likely negative correlation between the appendix and ulcerative colitis, the idea of the appendix being a vestigial organ should therefore be discarded.

PMID 27682122 — Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract.

Hydrogen sulfide (H₂S) is a Janus-faced molecule. On one hand, several toxic functions have been attributed to H₂S and exposure to high levels of this gas is extremely hazardous to health. On the other hand, H₂S delivery based clinical therapies are being developed to combat inflammation, visceral pain, oxidative stress related tissue injury, thrombosis and cancer. Since its discovery, H₂S has been found to have pleiotropic effects on physiology and health. H₂S is a gasotransmitter that exerts its effect on different systems, such as gastrointestinal, neuronal, cardiovascular, respiratory, renal, and hepatic systems. In the gastrointestinal tract, in addition to H₂S production by mammalian cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), H₂S is also generated by the metabolic activity of resident gut microbes, mainly by colonic Sulfate-Reducing Bacteria (SRB) via a dissimilatory sulfate reduction (DSR) pathway. In the gut, H₂S regulates functions such as inflammation, ischemia/ reperfusion injury and motility. H₂S derived from gut microbes has been found to be associated with gastrointestinal disorders such as ulcerative colitis, Crohn’s disease and irritable bowel syndrome. This underscores the importance of gut microbes and their production of H₂S on host physiology and pathophysiology.

PMID 24803247 — Commentary: Adjunct antibiotic combination therapy for ulcerative colitis—is it time to investigate Fusobacterium varium?

No abstract returned.

PMID 24714392 — Influences of the colonic microbiome on the mucous gel layer in ulcerative colitis.

The colonic mucus gel layer (MGL) is a critical component of the innate immune system acting as a physical barrier to microbes, luminal insults, and toxins. Mucins are the major component of the MGL. Selected microbes have the potential to interact with, bind to, and metabolize mucins. The tolerance of the host to the presence of these microbes is critical to maintaining MGL homeostasis. In disease states such as ulcerative colitis (UC), both the mucosa associated microbes and the constituent MGL mucins have been shown to be altered. Evidence is accumulating that implicates the potential for mucin degrading bacteria to negatively impact the MGL and its stasis. These effects appear more pronounced in UC.   This review is focused on the host-microbiome interactions within the setting of the MGL. Special focus is given to the mucolytic potential of microbes and their interactions in the setting of the colitic colon.

PMID 24489770 — Long-term alteration of intestinal microbiota in patients with ulcerative colitis by antibiotic combination therapy.

Previous work has demonstrated that intestinal bacteria, such as Fusobacterium varium (F. varium), contribute to the clinical activity in ulcerative colitis (UC); thus, an antibiotic combination therapy (amoxicillin, tetracycline, and metronidazole (ATM)) against F. varium can induce and maintain UC remission. Therefore, we investigated whether ATM therapy induces a long-term alteration of intestinal microbiota in patients with UC. Patients with UC were enrolled in a multicenter, randomized, double-blind, placebo-controlled study. Biopsy samples at the beginning of the trial and again at 3 months after treatment completion were randomly obtained from 20 patients. The terminal restriction fragment length polymorphism (T-RFLP) in mucosa-associated bacterial components was examined to assess the alteration of the intestinal microbiota. Profile changes of T-RFLP in mucosa-associated bacterial components were found in 10 of 12 patients in the treatment group and in none of 8 in the placebo group. Dice similarity coefficients using the unweighted pair group method with arithmetic averages (Dice-UPGMA) confirmed that the similarity of mucosal microbiota from the descending colon was significantly decreased after the ATM therapy, and this change was maintained for at least 3 months. Moreover, at 3 months after treatment completion, the F. varium/β-actin ratio, examined by real-time PCR using nested PCR products from biopsy samples, was reduced less than 40% in 8 of 12 treated patients, which was higher, but not significantly, than in 4 of 8 patients in the placebo group. Together, these results suggest that ATM therapy induces long-term alterations in the intestinal microbiota of patients with UC, which may be associated, at least in part, with clinical effects of the therapy.

PMID 25025717 — Mucus layers in inflammatory bowel disease.

The intestinal epithelium is covered with mucus with the main structural building block being the densely O-glycosylated MUC2 mucin. The intestinal epithelium is exposed to ingested material, our digestive machinery, and large amounts of microorganisms. Mucus is the first line of defense and aids to limit exposure to all these threats to the epithelium. In the small intestine, mucus acts as a matrix, which contains antimicrobial products, such as defensins and immunoglobulin A that limit epithelial exposure to the luminal bacteria. In the colon, the stratified inner mucus layer acts as a physical barrier excluding bacteria from the epithelium. Bacterial penetration of this normally restricted zone is observed in many colitis models and also in patients with ulcerative colitis. Mucus defects that allow bacteria to reach the epithelium and to stimulate an immune system response can lead to the development of intestinal inflammation. The current state of our knowledge concerning the function of the mucus layers and the main mucin component, MUC2, in inflammatory bowel disease is described in this review.

PMID 24945909 — Spontaneous colitis in Muc2-deficient mice reflects clinical and cellular features of active ulcerative colitis.

  • Journal: PloS one (2014)
  • DOI: 10.1371/journal.pone.0100217
  • URL: https://pubmed.ncbi.nlm.nih.gov/24945909/
  • Authors: Wenzel UA, Magnusson MK, Rydström A, Jonstrand C, Hengst J, Johansson ME, Velcich A, Öhman L

The colonic mucus layer plays a critical role in intestinal homeostasis by limiting contact between luminal bacteria and the mucosal immune system. A defective mucus barrier in animal models allows bacterial contact with the intestinal epithelium and results in spontaneous colitis. A defective mucus barrier is also a key feature of active ulcerative colitis (UC). Alterations in the immune compartment due to intestinal bacterial breach in mice lacking the colon mucus barrier have not been characterized and correlated to active UC. To characterize alterations in the immune compartment due to intestinal bacterial breach in Muc2-/- mice, which lack the colon mucus barrier, and correlate the findings to active UC. Bacterial contact with colon epithelium and penetration into colon tissue was examined in Muc2-/- mice and colon biopsies from patients with active UC using fluorescence microscopy and qPCR. Neutrophils, lymphocytes, CD103+ dendritic cell subsets and macrophages in colon from Muc2-/- mice and biopsies from UC patients were quantitated by flow cytometry. Inflamed UC patients and Muc2-/- mice had bacteria in contact with the colon epithelium. Bacterial rRNA was present in colonic mucosa in humans and Muc2-/- mice and in the draining lymph nodes of mice. Inflamed Muc2-/- mice and UC patients had elevated colon neutrophils, T cells and macrophages while a reduced frequency of CD103+ DCs was present in the inflamed colon of both mice and humans. The parallel features of the colon immune cell compartment in Muc2-/- mice and UC patients supports the usefulness of this model to understand the early phase of spontaneous colitis and will provide insight into novel strategies to treat UC.

PMID 23269735 — Longitudinal analyses of gut mucosal microbiotas in ulcerative colitis in relation to patient age and disease severity and duration.

  • Journal: Journal of clinical microbiology (2013)
  • DOI: 10.1128/JCM.02574-12
  • URL: https://pubmed.ncbi.nlm.nih.gov/23269735/
  • Authors: Fite A, Macfarlane S, Furrie E, Bahrami B, Cummings JH, Steinke DT, Macfarlane GT

Bacteria belonging to the normal colonic microbiota are associated with the etiology of ulcerative colitis (UC). Although several mucosal species have been implicated in the disease process, the organisms and mechanisms involved are unknown. The aim of this investigation was to characterize mucosal biofilm communities over time and to determine the relationship of these bacteria to patient age and disease severity and duration. Multiple rectal biopsy specimens were taken from 33 patients with active UC over a period of 1 year. Real-time PCR was used to quantify mucosal bacteria in UC patients compared to 18 noninflammatory bowel disease controls, and the relationship between indicators of disease severity and bacterial colonization was evaluated by linear regression analysis. Significant differences were detected in bacterial populations on the UC mucosa and in the control group, which varied over the study period. High clinical activity indices (CAI) and sigmoidoscopy scores (SS) were associated with enterobacteria, desulfovibrios, type E Clostridium perfringens, and Enterococcus faecalis, whereas the reverse was true for Clostridium butyricum, Ruminococcus albus, and Eubacterium rectale. Lactobacillus and bifidobacterium numbers were linked with low CAI. Only E. rectale and Clostridium clostridioforme had a high age dependence. These findings demonstrated that longitudinal variations in mucosal bacterial populations occur in UC and that bacterial community structure is related to disease severity.

PMID 24246979 — Mucus and the goblet cell.

The discovery of an inner mucus layer normally impervious to bacteria has changed our way of understanding the interaction between commensal bacteria and the host epithelial cells. This inner colon mucus layer is rapidly renewed and converted into the outer mucus layer by host controlled endogenous proteolytic processing. The mucus characteristics esteem from the properties of the main protein component of these layers, the MUC2 mucin. This forms an enormously large net-like structure that builds the laminated inner mucus layer that largely acts as a size exclusion filter excluding bacteria. In the absence of MUC2 mucin, there is no inner mucus layer and bacteria reach the epithelial cell surface, penetrate the crypts and are also found inside epithelial cells, something that leads to severe inflammation. Other mouse models that spontaneously develop colitis due to different defects, like an absent ion channel (Nhe3) or immunological mediators (Tlr5, IL-10), all also have a defective inner colon mucus layer. Human patients with active ulcerative colitis have this layer penetrable to bacteria and beads the size of bacteria. Some of the ulcerative colitis patients in remission have a normal mucus layer whereas others have a penetrable inner mucus layer. Together, this suggests that the inner mucus layer and its integrity is important for the protection of the colon epithelium and inhibiting activation of the immune system as in ulcerative colitis.

PMID 24204617 — Utilisation of mucin glycans by the human gut symbiont Ruminococcus gnavus is strain-dependent.

Commensal bacteria often have an especially rich source of glycan-degrading enzymes which allow them to utilize undigested carbohydrates from the food or the host. The species Ruminococcus gnavus is present in the digestive tract of ≥90% of humans and has been implicated in gut-related diseases such as inflammatory bowel diseases (IBD). Here we analysed the ability of two R. gnavus human strains, E1 and ATCC 29149, to utilize host glycans. We showed that although both strains could assimilate mucin monosaccharides, only R. gnavus ATCC 29149 was able to grow on mucin as a sole carbon source. Comparative genomic analysis of the two R. gnavus strains highlighted potential clusters and glycoside hydrolases (GHs) responsible for the breakdown and utilization of mucin-derived glycans. Transcriptomic and functional activity assays confirmed the importance of specific GH33 sialidase, and GH29 and GH95 fucosidases in the mucin utilisation pathway. Notably, we uncovered a novel pathway by which R. gnavus ATCC 29149 utilises sialic acid from sialylated substrates. Our results also demonstrated the ability of R. gnavus ATCC 29149 to produce propanol and propionate as the end products of metabolism when grown on mucin and fucosylated glycans. These new findings provide molecular insights into the strain-specificity of R. gnavus adaptation to the gut environment advancing our understanding of the role of gut commensals in health and disease.

PMID 21807247 — Mucosal biofilm communities in the human intestinal tract.

Complex and highly variable site-dependent bacterial ecosystems exist throughout the length of the human gastrointestinal tract. Until relatively recently, the majority of our information on intestinal microbiotas has come from studies on feces, or from aspirates taken from the upper gut. However, there is evidence showing that mucosal bacteria growing in biofilms on surfaces lining the gut differ from luminal populations, and that due to their proximity to the epithelial surface, these organisms may be important in modulating the host’s immune system and contributing to some chronic inflammatory diseases. Over the past decade, increasing interest in mucosal bacteria, coupled with advances in molecular approaches for assessing microbial diversity, has begun to provide some insight into the complexity of these mucosa-associated communities. In gastrointestinal conditions such as inflammatory bowel diseases (ulcerative colitis, Crohn’s disease), it has been shown that a dysbiosis exists in microbial community structure, and that there is a reduction in putatively protective mucosal organisms such as bifidobacteria. Therefore, manipulation of mucosal communities may be beneficial in restoring normal functionality in the gut, thereby improving the immune status and general health of the host. Biofilm structure and function has been studied intensively in the oral cavity, and as a consequence, mucosal communities in the mouth will not be covered in this chapter. This review addresses our current knowledge of mucosal populations in the gastrointestinal tract, changes that can occur in community structure in disease, and therapeutic modulation of biofilm composition by antibiotics, prebiotics, and probiotics.

PMID 20805871 — Bacteria penetrate the inner mucus layer before inflammation in the dextran sulfate colitis model.

Protection of the large intestine with its enormous amount of commensal bacteria is a challenge that became easier to understand when we recently could describe that colon has an inner attached mucus layer devoid of bacteria (Johansson et al. (2008) Proc. Natl. Acad. Sci. USA 105, 15064-15069). The bacteria are thus kept at a distance from the epithelial cells and lack of this layer, as in Muc2-null mice, allow bacteria to contact the epithelium. This causes colitis and later on colon cancer, similar to the human disease Ulcerative Colitis, a disease that still lacks a pathogenetic explanation. Dextran Sulfate (DSS) in the drinking water is the most widely used animal model for experimental colitis. In this model, the inflammation is observed after 3-5 days, but early events explaining why DSS causes this has not been described. When mucus formed on top of colon explant cultures were exposed to 3% DSS, the thickness of the inner mucus layer decreased and became permeable to 2 microm fluorescent beads after 15 min. Both DSS and Dextran readily penetrated the mucus, but Dextran had no effect on thickness or permeability. When DSS was given in the drinking water to mice and the colon was stained for bacteria and the Muc2 mucin, bacteria were shown to penetrate the inner mucus layer and reach the epithelial cells already within 12 hours, long before any infiltration of inflammatory cells. DSS thus causes quick alterations in the inner colon mucus layer that makes it permeable to bacteria. The bacteria that reach the epithelial cells probably trigger an inflammatory reaction. These observations suggest that altered properties or lack of the inner colon mucus layer may be an initial event in the development of colitis.

PMID 20216533 — Newly developed antibiotic combination therapy for ulcerative colitis: a double-blind placebo-controlled multicenter trial.

  • Journal: The American journal of gastroenterology (2010)
  • DOI: 10.1038/ajg.2010.84
  • URL: https://pubmed.ncbi.nlm.nih.gov/20216533/
  • Authors: Ohkusa T, Kato K, Terao S, Chiba T, Mabe K, Murakami K, Mizokami Y, Sugiyama T

Fusobacterium varium may contribute to ulcerative colitis (UC). We conducted a double-blind placebo-controlled multicenter trial to determine whether antibiotic combination therapy induces and/or maintains remission of active UC. Patients with chronic mild-to-severe relapsing UC were randomly assigned to oral amoxicillin 1500 mg/day, tetracycline 1500 mg/day, and metronidazole 750 mg/day, vs. placebo, for 2 weeks, and then followed up. The primary study end point was clinical response (Mayo score at 3 months after treatment completion) and secondary end points were clinical and endoscopic score improvements at 12 months. Anti-F. varium antibodies were measured by enzyme-linked immunosorbent assay. Treatment and placebo groups each had 105 subjects. At the primary end point, response rates were significantly greater with antibiotics than with placebo (44.8 vs. 22.8%, P=0.0011). Endoscopic scores significantly improved at 3 months (P=0.002 vs. placebo). Remission rates were 19.0% (antibiotics) vs. 15.8% (placebo) at 3 months (P=0.59). At the secondary end point, response rates were significantly greater with antibiotics than with placebo (49.5 vs. 21.8%, respectively, P<0.0001). Endoscopic scores were significantly improved at 12 months after antibiotic treatment (P=0.002 vs. placebo). Remission rates had improved to 26.7% with antibiotics vs. 14.9% for placebo, at 12 months (P=0.041). F. varium antibody titers decreased in responders but not in nonresponders, and more in the antibiotic than in the placebo group. More pretreatment steroid-dependent UC patients discontinued corticosteroids after treatment completion (6 months: 28.6 vs. 11.8%, respectively, P=0.046; 9 months: 34.7 vs. 13.7%, respectively, P=0.019; and 12 months: 34.7 vs. 13.7%, respectively, P=0.019). These effects were greater in the subanalysis of the active group (Mayo scores of 6-12) than in that of total cases (0-12). No serious drug-related toxicities occurred. The 2-week triple antibiotic therapy produced improvement, remission, and steroid withdrawal in active UC more effectively than a placebo.

PMID 17642254 — [Clinical significance of sulfate-reducing bacteria for ulcerative colitis].

Ulcerative colitis(UC) is colon localized disease. Broad epithelial cell damage, crypt abscesses and accumulation of neutrophils are recognized for UC. Although the cause of UC is indistinct at this time, there is a growing consensus that abnormal intestinal microflora would be related with UC. There have been several evidences that excessive production of hydrogen sulfide by bacteria in colon would be associated with UC. Sulfate reducing bacteria are able to utilize sulfate as an electron receptor for dissimilation of organic substrate and hydrogen gas, resulting in generating toxic hydrogen sulfide. This review is dealt with the association between sulfate reducing bacteria and UC in aetiology and bacterial pathogenesis.

PMID 16334443 — Effectiveness of antibiotic combination therapy in patients with active ulcerative colitis: a randomized, controlled pilot trial with long-term follow-up.

  • Journal: Scandinavian journal of gastroenterology (2005)
  • DOI: 10.1080/00365520510023648
  • URL: https://pubmed.ncbi.nlm.nih.gov/16334443/
  • Authors: Ohkusa T, Nomura T, Terai T, Miwa H, Kobayashi O, Hojo M, Takei Y, Ogihara T

It is proposed that Fusobacterium varium might be one of the elusive pathogenic factors in ulcerative colitis (UC). Our goal was to assess whether an antibiotic combination therapy against F. varium is effective for induction and maintenance of remission of UC. Twenty chronic, active UC patients with F. varium infection were enrolled consecutively and were randomly assigned to receive amoxicillin, tetracycline or metronidazole per os for 2 weeks (treatment group; n=10), or no antibiotics (control group; n=10). F. varium was sensitive to the antibiotics. Symptom assessment, endoscopic and histological evaluations were performed blind before enrollment at 3-5 months and 12-14 months after the treatment. Serum immunoglobulins to F. varium were measured using an enzyme-linked immunosorbent assay (ELISA). Immunohistochemical detection of F. varium in biopsy specimens was carried out using the avidin-biotin complex method. The clinical activity, endoscopic and histological scores in the treatment group decreased significantly at 3-5 and 12-14 months after the end of treatment compared with those in the control group (p=0.001-0.036). The remission rate in the treatment group was higher than that in the control group (p=0.037). In addition, the titers of antibody to F. varium and the F. varium density in the mucosa decreased at both the short- and long-term follow-ups in the treatment group (p=0.0002-0.049). No serious drug-related toxicity was observed during the trial. The 2-week antibiotic combination therapy against F. varium was effective and safe in patients with chronic, active ulcerative colitis in this long-term follow-up study.

PMID 15813838 — Mucosa-associated bacteria in ulcerative colitis before and after antibiotic combination therapy.

  • Journal: Alimentary pharmacology & therapeutics (2005)
  • DOI: 10.1111/j.1365-2036.2005.02428.x
  • URL: https://pubmed.ncbi.nlm.nih.gov/15813838/
  • Authors: Nomura T, Ohkusa T, Okayasu I, Yoshida T, Sakamoto M, Hayashi H, Benno Y, Hirai S

We proposed that Fusobacterium varium is one of the causative agents in ulcerative colitis. To examine the efficacy of antibiotic combination therapy against F. varium and to investigate the mucosa-associated bacteria before and after the therapy using a new molecular approach. Twenty patients with ulcerative colitis were randomly assigned into the antibiotic treatment group (amoxicillin, tetracycline and metronidazole for 2 weeks) and no-antibiotics group. Clinical assessment, colonoscopic and histological evaluations were performed at 0 and 3-5 months after the treatment. DNA from mucosal bacteria was isolated from biopsy specimens. We investigated the mucosa-associated bacterial components by terminal restriction fragment length polymorphism with the restriction enzyme HhaI and MspI, and quantified the change in the number of bacteria by real-time polymerase chain reaction. Immunohistochemical detection of F. varium in biopsy specimens was also performed. After the treatment, the clinical assessment, colonoscopic and histological scores improved in the antibiotic group compared with the control group. Three peaks of terminal restriction fragment length polymorphism decreased after treatment only in the antibiotic group. Eubacterium rectale, Dorea formicigenerans, Clostridium clostridioforme and F. varium were included in these peaks. Based on the real-time polymerase chain reaction study, only F. varium was significantly reduced after treatment. In the immunostaining, post-treatment scores in treatment group were significantly lower than that in control group. Antibiotics combination therapy was effective for ulcerative colitis. The number of mucosa-associated F. varium significantly decreased after the treatment.

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