Microbial ecology of the murine gut associated with the development of dextran sodium sulfate-induced colitis

Background: Dextran sodium sulfate (DSS) is used to induce murine colitis. Although the exact mechanism by which DSS administration causes disease is unknown, evidence suggests that the resident bacteria play a role in the development of murine DSS colitis, analogous to their role in human inflammatory bowel diseases. Methods: C57BL/6 mice received 5% DSS in the drinking water and were euthanized 3 days and 14 days after the initiation of DSS treatment. Culture-independent methods were used to follow changes in the community structure of the gut's microbiota following DSS treatment. Histologic evidence of disease and changes in host gene expression were assessed. Results: Histologic colitis was minimal in DSS-treated animals at 3 days, but severe after 14 days. Analysis of 16S rRNA-encoding gene clone libraries demonstrated that the microbial communities in the ceca of DSS-treated mice were distinct from those in control mice. The microbiota in the cecum of DSS-treated animals was characterized by an overall decrease in microbial richness, an increase in members of the phylum Verrucomicrobia, and decrease in Tenericutes. Changes in the host's inflammatory response and microbial communities occurred before the histologic appearance of severe disease in the colon, but were seen concurrently in the cecum. Conclusions: DSS administration is associated with reproducible changes in the gut microbial diversity of mice. Microbial and immunological changes appeared before the development of severe inflammation in the colon. This indicates that these changes in microbial community may play role in the potentiation of the abnormal inflammatory response seen in DSS-treated animals. (Inflamm Bowel Dis 2011)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83471/1/21462_ftp.pd

Association between Helicobacter pylori infection and inflammatory bowel disease: A meta-analysis and systematic review of the literature

Background: Epidemiologic data suggest a protective effect of Helicobacter pylori infection against the development of autoimmune disease. Laboratory data illustrate H. pylori 's ability to induce immune tolerance and limit inflammatory responses. Numerous observational studies have investigated the association between H. pylori infection and inflammatory bowel disease (IBD). Our aim was to perform a systematic review and meta-analysis of this association. Methods: Medline, EMBASE, bibliographies, and meeting abstracts were searched by 2 independent reviewers. Of 369 abstracts reviewed, 30 promising articles were reviewed in detail. Twenty-three studies met our inclusion criteria (subject N = 5903). Meta-analysis was performed with the metan command in Stata 10.1. Results: Overall, 27.1% of IBD patients had evidence of infection with H. pylori compared to 40.9% of patients in the control group. The estimated relative risk of H. pylori infection in IBD patients was 0.64 (95% confidence interval [CI]: 0.54–0.75). There was significant heterogeneity in the included studies that could not be accounted for by the method of IBD and H. pylori diagnosis, study location, or study population age. Conclusions: These results suggest a protective benefit of H. pylori infection against the development of IBD. Heterogeneity among studies and the possibility of publication bias limit the certainty of this finding. Further studies investigating the effect of eradication of H. pylori on the development of IBD are warranted. Because environmental hygiene and intestinal microbiota may be strong confounders, further mechanistic studies in H. pylori mouse models are also necessary to further define the mechanism of this negative association. (Inflamm Bowel Dis 2009;)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75792/1/21116_ftp.pd

CCR2 mediates Helicobacter pyloriâ induced immune tolerance and contributes to mucosal homeostasis

BackgroundWe previously demonstrated that H. pylori infection leads to increased induction of regulatory T cells in local and systemic immune compartments. Here, we investigate the role of CCR2 in the tolerogenic programing of dendritic cells in a mouse model of H. pylori infection.Materials and MethodsCCR2 deficient (CCR2KO) mice and wildâ type (Wt) mice infected with H. pylori SS1 strain were analyzed by qPCR and FACS analysis. In vitro, bone marrowâ derived DC on day 6 from CCR2KO and Wt mice cocultured with or without H. pylori were examined to determine the impact of CCR2 signaling on dendritic cells function by qPCR, ELISA, and FACS analyses.ResultsAcute H. pylori infection was associated with a threefold increase in CCR2 mRNA expression in the gastric mucosa. H. pyloriâ infected CCR2KO mice exhibited a higher degree of mucosal inflammation, that is, increased gastritis scores and proâ inflammatory cytokine mRNA levels, but lower degree of H. pylori gastric colonization compared to infected Wt mice. Peripheral H. pyloriâ specific immune response measured in the CCR2KO spleen was characterized by a higher Th17 response and a lower Treg response. In vitro, CCR2KO bone marrowâ derived DC was less mature and shown a lower Treg/Th17 ratio. Moreover, blockade of CCR2 signaling by MCPâ 1 neutralizing antibody inhibited H. pyloriâ stimulated bone marrowâ derived DC maturation.ConclusionsOur results indicate that CCR2 plays an essential role in H. pyloriâ induced immune tolerance and shed light on a novel mechanism of CCR2â dependent DC Treg induction, which appears to be important in maintaining mucosal homeostasis during H. pylori infection.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136416/1/hel12366.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136416/2/hel12366_am.pd

A Pilot Study of the Association of Low Plasma Adiponectin and Barrett's Esophagus

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72851/1/j.1572-0241.2008.01823.x.pd

Prior Helicobacter pylori infection ameliorates Salmonella typhimurium-induced colitis: Mucosal crosstalk between stomach and distal intestine

Background: Helicobacter pylori infection is associated with a lower risk of chronic autoimmune diseases including inflammatory bowel disease (IBD). H. pylori modulates the gastric immune response, decreasing the local inflammatory response to itself. In mice, chronic Salmonella typhimurium infection induces colitis similar to Crohn's disease, characterized by inflammation, which progresses toward fibrosis. The aim of this study was to determine whether prior H. pylori infection acts at a distance to modulate the immune response of S. typhimurium -induced colitis. Methods: Mice were infected with the mouse-adapted strain of H. pylori (SS1), followed by infection with S. typhimurium . The effect of H. pylori on colitis was determined by gross pathology, histopathology, cytokine response, and development of fibrosis in the cecum. Gastritis and systemic immune response was measured in response to infection. Results: H. pylori suppresses the Th17 response to S. typhimurium infection in the mouse cecum, but does not alter the Th2 or T-regulatory response or the development of fibrosis. H. pylori infection induces IL-10 in the mesenteric lymph nodes, suggesting an extragastric mechanism for immunomodulation. H. pylori / S. typhimurium coinfection decreases inflammation in both the cecum and the stomach. Conclusions: This study demonstrates a potential mechanism for the negative association between H. pylori and IBD in humans. H. pylori represses the lower gastrointestinal tract Th17 response to bacterially induced colitis via extragastric immunomodulatory effects, illustrating immunological crosstalk between the upper and lower gastrointestinal tract. (Inflamm Bowel Dis 2011;)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84386/1/21489_ftp.pd

Shortâ term and longâ term impacts of Helicobacter pylori eradication with reverse hybrid therapy on the gut microbiota

Background and AimsAntiâ Helicobacter pylori therapy may lead to the growth of pathogenic or antibioticâ resistant bacteria in the gut. The study aimed to investigate the shortâ term and longâ term impacts of H. pylori eradication with reverse hybrid therapy on the components and macrolide resistance of the gut microbiota.MethodsHelicobacter pyloriâ related gastritis patients were administered a 14â day reverse hybrid therapy. Fecal samples were collected before treatment and at the end of week 2, week 8, and week 48. The V3â V4 region of the bacterial 16S rRNA gene in fecal specimens was amplified by polymerase chain reaction and sequenced on Illumina MiSeq platform. Additionally, amplification of erm(B) gene (encoding erythromycin resistance methylase) was performed.ResultsReverse hybrid therapy resulted in decreased relative abundances of Firmicutes (from 62.0% to 30.7%; P < 0.001) and Actinobacteria (from 3.4% to 0.6%; 0.032) at the end of therapy. In contrast, the relative abundance of Proteobacteria increased from 10.2% to 49.1% (0.002). These microbiota alterations did not persist but returned to the initial levels at week 8 and week 48. The amount of erm(B) gene in fecal specimens was comparable with the pretreatment level at week 2 but increased at week 8 (0.025) and then returned to the pretreatment level by week 48.ConclusionsHelicobacter pylori eradication with reverse hybrid therapy can lead to shortâ term gut dysbiosis. The amount of erm(B) gene in the stool increased transiently after treatment and returned to the pretreatment level at 1â year postâ treatment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152555/1/jgh14736_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152555/2/jgh14736.pd

Depression, antidepressant medications, and risk of Clostridium difficile infection

Abstract Background An ancillary finding in previous research has suggested that the use of antidepressant medications increases the risk of developing Clostridium difficile infection (CDI). Our objective was to evaluate whether depression or the use of anti-depressants altered the risk of developing CDI, using two distinct datasets and study designs. Methods In Study 1, we conducted a longitudinal investigation of a nationally representative sample of older Americans (n = 16,781), linking data from biennial interviews to physician and emergency department visits, stays in hospital and skilled nursing facilities, home health visits, and other outpatient visits. In Study 2, we completed a clinical investigation of hospitalized adults who were tested for C. difficile (n = 4047), with cases testing positive and controls testing negative. Antidepressant medication use prior to testing was ascertained. Results The population-based rate of CDI in older Americans was 282.9/100,000 person-years (95% confidence interval (CI)) 226.3 to 339.5) for individuals with depression and 197.1/100,000 person-years for those without depression (95% CI 168.0 to 226.1). The odds of CDI were 36% greater in persons with major depression (95% CI 1.06 to 1.74), 35% greater in individuals with depressive disorders (95% CI 1.05 to 1.73), 54% greater in those who were widowed (95% CI 1.21 to 1.95), and 25% lower in adults who did not live alone (95% CI 0.62 to 0.92). Self-reports of feeling sad or having emotional, nervous or psychiatric problems at baseline were also associated with the later development of CDI. Use of certain antidepressant medications during hospitalization was associated with altered risk of CDI. Conclusions Adults with depression and who take specific anti-depressants seem to be more likely to develop CDI. Older adults who are widowed or who live alone are also at greater risk of CDI.http://deepblue.lib.umich.edu/bitstream/2027.42/112859/1/12916_2012_Article_763.pd

Multiple light scattering in nematic liquid crystals

We present a rigorous treatment of the diffusion approximation for multiple light scattering in anisotropic random media, and apply it to director fluctuations in a nematic liquid crystal. For a typical nematic material, 5CB, we give numerical values of the diffusion constants $D_{\|}$ and $D_{\perp}$. We also calculate the temporal autocorrelation function measured in Diffusing Wave Spectroscopy.Comment: 5 pages RevTeX, 1 postscript figure, to be published in Phys. Rev. E (Rapid Communication

Equivalent efficacies of reverse hybrid and concomitant therapies in first- line treatment of Helicobacter pylori infection

Background and AimConcomitant therapy is a recommended first- line treatment for Helicobacter pylori infection in most national or international consensuses. Reverse hybrid therapy is a modified 14- day concomitant therapy without clarithromycin and metronidazole in the final 7 days. This study aims to test whether 14- day reverse hybrid therapy is non- inferior to 14- day concomitant therapy in the first- line treatment of H. pylori infection.MethodsHelicobacter pylori- infected adult patients were randomly assigned to receive either reverse hybrid therapy (dexlansoprazole 60 mg o.d. plus amoxicillin 1 g b.d. for 14 days, and clarithromycin 500 mg plus metronidazole 500 mg b.d. for initial 7 days) or concomitant therapy (dexlansoprazole 60 mg once o.d. plus amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg b.d. for 14 days). H. pylori status was assessed 6 weeks after the end of treatment.ResultsHelicobacter pylori- infected participants (n = 248) were randomized to receive either 14- day reverse hybrid therapy (n = 124) or 14- day concomitant therapy (n = 124). Intention- to- treat analysis demonstrated that the two therapies had comparable eradication rate (95.2% vs 93.5%; 95% confidence interval, - 4.0% to 7.4%; P = 0.582). However, reverse hybrid therapy had a much lower frequency of adverse events than concomitant therapy (20.2% vs 38.7%, P = 0.001). The two therapies exhibited comparable drug adherence (93.5% vs 87.9%, P = 0.125).ConclusionsFourteen- day reverse hybrid therapy and 14- day concomitant therapy are equivalent in efficacy for the first- line treatment of H. pylori infection. However, reverse hybrid therapy has fewer adverse events compared with concomitant therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163472/2/jgh15034_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163472/1/jgh15034.pd