Radiation induces proinflammatory dysbiosis: transmission of inflammatory susceptibility by host cytokine induction.

OBJECTIVE: Radiation proctitis (RP) is a complication of pelvic radiotherapy which affects both the host and microbiota. Herein we assessed the radiation effect on microbiota and its relationship to tissue damage using a rectal radiation mouse model. DESIGN: We evaluated luminal and mucosa-associated dysbiosis in irradiated and control mice at two postradiation time points and correlated it with clinical and immunological parameters. Epithelial cytokine response was evaluated using bacterial-epithelial co-cultures. Subsequently, germ-free (GF) mice were colonised with postradiation microbiota and controls and exposed to radiation, or dextran sulfate-sodium (DSS). Interleukin (IL)-1ß correlated with tissue damage and was induced by dysbiosis. Therefore, we tested its direct role in radiation-induced damage by IL-1 receptor antagonist administration to irradiated mice. RESULTS: A postradiation shift in microbiota was observed. A unique microbial signature correlated with histopathology. Increased colonic tumor necrosis factor (TNF)α, IL-1ß and IL-6 expression was observed at two different time points. Adherent microbiota from RP differed from those in uninvolved segments and was associated with tissue damage. Using bacterial-epithelial co-cultures, postradiation microbiota enhanced IL-1ß and TNFα expression compared with naïve microbiota. GF mice colonisation by irradiated microbiota versus controls predisposed mice to both radiation injury and DSS-induced colitis. IL-1 receptor antagonist administration ameliorated intestinal radiation injury. CONCLUSIONS: The results demonstrate that rectal radiation induces dysbiosis, which transmits radiation and inflammatory susceptibility and provide evidence that microbial-induced radiation tissue damage is at least in part mediated by IL-1ß. Environmental factors may affect the host via modifications of the microbiome and potentially allow for novel interventional approaches via its manipulation.

[Acute cytomegalovirus proctitis in a immunocompetent patient]. / Rectite aiguë à cytomégalovirus chez un patient immunocompétent.

Cases of CMV proctitis are frequently reported in immunocompromised patients. However, some cases of CMV proctitis are linked to a CMV primary infection and to unprotected anal intercourse in immunocompetent patients. The most common symptom is bloody diarrhea (hemorrhagic colitis). The endoscopic exam can present in distincts forms. The diagnostic is based on a set of clinical, biological, endoscopic and histological arguments. The prognosis of the disease is favorable. The treatment is supportive. A research on other sexually transmitted diseases must be conducted.

Des cas de rectite à cytomégalovirus (CMV) sont fréquemment rapportés chez des patients immunodéprimés. Cependant, certains cas de rectite à CMV sont associés à une primo-infection à CMV et des rapports anaux non protégés chez une personne immunocompétente. La diarrhée hémorragique est le symptôme le plus fréquent. La présentation endoscopique est variée. Le diagnostic repose sur un faisceau d'arguments cliniques, biologiques, endoscopiques et histologiques. Le pronostic de l'affection est favorable. Le traitement est simplement supportif. Une recherche d'autres maladies sexuellement transmissibles doit être réalisée.

Reactivated cytomegalovirus proctitis in an immunocompetent patient presenting as nosocomial diarrhea: a case report and literature review.

BACKGROUND: Reactivated cytomegalovirus (CMV) infection has been known to cause significant morbidity and mortality in immunocompromised patients. However, CMV disease rarely develops in immunocompetent patients, and reported cases often present with a mild, self-limiting course, without severe life-threatening sequelae. While the colon is the most common gastrointestinal site affected by CMV disease in immunocompetent patients, rectal involvement is rarely reported. CMV proctitis can present in two distinct forms, primary and reactivated. However, reactivated CMV proctitis is rarely reported as a causative etiology of nosocomial diarrhea, except in transplant patients. Herein we present a case of reactivated CMV proctitis in an immunocompetent patient, presenting as nosocomial diarrhea. Previously reported cases of reactivated CMV proctitis in immunocompetent patients are also reviewed. CASE PRESENTATION: A 79-year-old female was admitted because of metabolic encephalopathy caused by dehydration and hypernatremia. The patient's consciousness level returned rapidly after fluid supplementation. However, she subsequently presented with abdominal pain and diarrhea on day 8 of admission. Abdominal contrast-enhanced computed tomography on day 10 of admission demonstrated inflammation around the rectum, suggesting proctitis. Colonoscopy on day 16 of admission showed a giant ulcer at the rectum. Pathology of rectal biopsy confirmed CMV infection. The patient recovered without sequelae after 38 days of valganciclovir treatment. Follow-up colonoscopy revealed a healed ulcer over the rectum. Ten cases in the literature, plus our case, with reactivated CMV proctitis in immunocompetent patients were reviewed. We found that most patients were elderly (mean, 72 years) with a high prevalence of diabetes mellitus (54.5%). Cardinal manifestations are often non-specific (diarrhea, hematochezia, tenesmus), and eight (72.7%) developed CMV proctitis following a preceding acute, life-threatening disease, rather than as an initial presentation on admission. These manifestations frequently develop during hospitalization, and are thus often regarded as nosocomial diarrhea. CONCLUSIONS: Clinicians should be aware of the possibility of nosocomial onset of reactivated CMV proctitis in patients hospitalized due to a preceding critical illness, although the benefits of antiviral therapy remain unclear.

[IMMUNOHISTOCHEMICAL AND CYTOLOGICAL ASSESSMENT OF LOCAL INFLAMMATORY REACTION IN THE EARLY POSTOPERATIVE PERIOD IN PATIENTS UNDERGOING SURGERY FOR COMPLEX FORMS OF ACUTE PARAPROCTITIS].

The optimal time to fulfill the second (plastic) phase delayed early radical surgery in patients over the complicated forms of acute paraproctitis. On the 7th day after the opening of an abscess in a smear from the surface layer of the wound inflammatory regenerative cytogram type was observed in 66.8% of patients, early regenerative type--at 33.2%. On the 10th day was observed regenerative cytogram type. The dynamics of the concentration of cytokines in wound fluid on the 7th day showed a favorable course of wound healing process, without increasing the levels of proinflammatory cytokines, which allowed to perform the second stage of early delayed surgery in 7-10 days.

Long-term outcomes of patients with ulcerative proctitis: Analysis from a large referral centre cohort.

INTRODUCTION: Long-term outcomes of patients with ulcerative proctitis (UP) have been poorly investigated, since these patients are excluded from participation in randomized controlled clinical trials. OBJECTIVE: The aim of this study was to investigate the prognostic and therapeutic long-term outcomes of patients with UP. METHODS: A retrospective study of patients with UP followed at our referral centre between 1 January 1998 and 1 January 2019 was performed. Treatment success was defined as clinical response (significant improvement in UP-related symptoms) and endoscopic response (mayo endoscopic sub-score of 0 or 1) if available at last follow-up. RESULTS: From a total of 1561 patients with ulcerative colitis, 118 patients with UP were identified. A total of 36 (31%) patients were refractory to rectal and oral therapy with 5-ASA and corticosteroids, necessitating azathioprine as monotherapy in 19 (16%) patients and/or biological therapies in 33 (28%) patients. After a median follow-up of 71 months (interquartile range 29-149 months), treatment success was observed in 103/118 (87%) UP patients and in 25/36 (69%) patients with refractory UP. Clinical response rates were significantly higher for refractory UP patients treated with biologicals (23/33; 70%) compared to ones treated with azathioprine (2/19; 11%; p = 0.001). CONCLUSION: Good clinical outcomes were recorded in UP, with treatment success in 87% of patients. Nevertheless, 28% needed escalation to biologicals. Long-term outcome in patients on biologicals was superior to azathioprine.

Effects of Supplemental Calcium and Vitamin D on Expression of Toll-Like Receptors and Phospho-IKKα/ß in the Normal Rectal Mucosa of Colorectal Adenoma Patients.

Chronic inflammation in the colorectum, a significant contributor to colorectal carcinogenesis, can be triggered by the activation of proinflammatory signaling pathways such as those initiated by Toll-like receptors (TLR) and nuclear factor κB (NF-κB). Although experimental evidence supports calcium and vitamin D potentially modifying these proinflammatory pathways in the colorectum, human data in these regards are scarce. We investigated supplemental calcium (1,200 mg daily) and/or vitamin D3 (1,000 IU daily) effects on inflammatory signaling pathway-related biomarkers in a subset of 105 participants from a colorectal adenoma recurrence chemoprevention clinical trial. We assessed expression of TLR4 and TLR5, which recognize the bacterial components lipopolysaccharides and flagellin, respectively, and phospho-IKKα/ß (pIKKα/ß), a biomarker of inflammation, in the normal-appearing rectal crypt epithelium and stroma using standardized, automated immunohistochemistry and quantitative image analysis. Following 1 year of treatment, TLR4, TLR5, and pIKKα/ß expression in the rectal mucosa did not statistically significantly change with vitamin D or calcium supplementation, taken alone or in combination. Several baseline participant characteristics, including body mass index, history of sessile serrated adenomas, high red/processed meat intake, and high levels of rectal epithelial cell proliferation (as measured by MIB-1/Ki-67), were associated with higher baseline expression of TLRs or pIKKα/ß. Our findings suggest that vitamin D and calcium may have no substantial effect on the investigated biomarkers. However, several modifiable lifestyle factors may be associated with TLRs and pIKKα/ß expression in the normal rectal mucosa, supporting their future investigation as potentially treatable, preneoplastic risk factors for colorectal neoplasms. Cancer Prev Res; 11(11); 707-16. ©2018 AACR.

Immunohistochemical changes in morphologically involved and uninvolved colonic mucosa of patients with idiopathic proctitis.

Alterations in secretory component, IgA, IgG, and IgM were studied by immunofluorescent techniques in mucosal biopsy specimens obtained at colonoscopy from inflamed and grossly uninvolved colonic mucosa from 12 patients with idiopathic proctitis. Parotid-salivary secretory component and IgA and serum immunoglobulins were also investigated. Decreased secretory IgA was observed in the epithelium of all grossly involved rectal mucosa and in 40% of proximal normal mucosa. Salivary secretory IgA was not diminished. These observations suggest that a local immune defect may be pathogenetically related to idiopathic proctitis.

El Linfogranuloma venéreo rectal: presentación clínica emergente / Rectal lymphogranuloma venereum: an emergent clinical presentation

El linfogranuloma venéreo (LGV) es una enfermedad de transmisión sexual (ETS) poco frecuente causada por los serotipos L1, L2 y L3 de Chlamydia trachomatis.Desde hace más de una década se produjo un aumento de la incidencia de proctitis por LGV casi exclusivamente en hombres que tienen sexo con hombres con prácticas sexuales de riesgo para ETS.Se presentan cuatro casos con LGV rectal

Lymphogranuloma venereum is a rare sexually transmitted infection (STI) caused by serotypes L1, L2 and L3 of Chlamydia trachomatis.For over a decade, there has been a considerable increase in the incidence of LGV proctitis in almost exclusively men who have sex with men with STI risk behaviors.Four cases of rectal LGV are reported

Allergic proctitis and gastroenteritis in children. Clinical and mucosal biopsy features in 53 cases.

We have reviewed 53 cases of allergic disorders of the gastrointestinal tract in children, including 15 with principal effects in the rectum (allergic proctitis) and 38 with dominant involvement of the upper and mid portions of the gut (allergic gastroenteritis). Most cases of allergic proctitis had their onset at less than 6 months of age, and all were under 2 years old when they presented with rectal bleeding alone or in combination with diarrhea. Rectal mucosal biopsy revealed in most cases a diffuse increase of eosinophils in the lamina propria together with a focal infiltration of the epithelium by eosinophils. Cases of allergic gastroenteritis affected all age groups and had a lower frequency of overt rectal bleeding. More common were other symptoms (vomiting, pain, and weight loss), an allergic history, anemia, blood eosinophilia, and increased serum IgE. Mucosal biopsy abnormalities were present in the gastric antrum in all cases sampled, the small intestine in 79%, the esophagus in 60%, and the gastric corpus in 52%. The lesions were usually diffuse and marked in the antrum and esophagus; in contrast, they tended to be focal and mild in the small intestine and gastric corpus. All cases of proctitis responded to a dietary change by cessation of symptoms without recurrences, whereas most of those with gastroenteritis had multiple relapses and required corticosteroid therapy.

Inflammatory cells in graft-versus-host disease on the rectum: immunopathologic analysis.

The inflammatory infiltrate of acute rectal graft-versus-host disease (GVHD) was investigated by indirect immunofluorescence. Twenty biopsies from 11 allogeneic bone marrow transplant recipients were studied in four groups: biopsies before transplantation; biopsies after transplantation without GVHD; biopsies from patients with extra-intestinal GVHD only; and biopsies from patients with intestinal GVHD. Total T cell numbers (CD2+, CD3+) in the lamina propria differed little in the four groups. CD4+ lymphocytes appeared to be decreased in GVHD while CD8+ lymphocytes were significantly increased (p less than 0.01), thus significantly lowering the CD4/CD8 ratio. In pre-transplant patients and in those without GVHD this ratio resembled that in normal peripheral blood (1.44 +/- 0.5 and 2.46 +/- 1.3, respectively) but was significantly lower in both extraintestinal (0.71 +/- 0.08) and intestinal GVHD (0.56 +/- 0.08) (p less than 0.05). Acute intestinal GVHD was marked by a fourfold increase in CD57+ lymphoid cells within the epithelium and the lamina propria (p less than 0.05). The recognition of CD57+ cells, which may include natural killer-like cells, within rectal lymphoid infiltrates suggests a possible role for non-HLA restricted effector cells in GVHD of the rectum.

Circulating auto-antibody against hepatoma-derived growth factor (HDGF) in patients with ulcerative colitis.

BACKGROUND/AIMS: Various circulating auto-antibodies have been reported in patients with ulcerative colitis. Hepatoma-derived growth factor (HDGF) is a mitogen, localized dominantly in the nucleus of proliferating cells. In this study, we demonstrated the circulating anti-HDGF auto-antibody and investigated its clinical roles in patients with ulcerative colitis. METHODOLOGY: Anti-HDGF IgG antibodies were measured by the enzyme-linked immunosorbent assay with recombinant HDGF in 20 healthy volunteers and 40 patients with ulcerative colitis. RESULTS: Circulating anti-HDGF antibody was detected in the serum of a patient with total colitis by Western blotting. Anti-HDGF auto-antibodies were detected at 65.6% in the serum of patients with total/left-sided colitis, compared with healthy subjects at 10%. During active stage, the circulating anti-HDGF auto-antibodies were detected at a higher frequency of 78.3% than those in remission stage at 37.5%. Furthermore, the titers during active colitis were higher than those during the remission stage. Anti-HDGF auto-antibodies were not detected in any patients with proctitis. CONCLUSIONS: These findings suggest that anti-HDGF auto-antibodies in the serum of patients with ulcerative colitis would help to classify the total/left-sided colitis from proctitis, and the serial measurement of the titer would also be a good marker for the active colitis.

[Lysosomal-cation test in the control of treatment of acute proctological diseases]. / Lizosomal'no-kationnyi test pri kontrole lecheniia urgentnykh proktologicheskikh zabolevanii.

An express evaluation of the functional state of neutrophil granulocytes by the indications of the lysosomal-cationic test are thought to be a necessary addition to routine clinico-laboratory methods of assessment of the wound process in patient with the suppurating epithelial coccygeal canal and acute paraproctitis. Use of cytochemical indices allow the antibacterial therapy to be optimized in patients with suppurating epithelial coccygeal canal and thus substantially decrease the amount of complications in the postoperative period.

Potential role of enterohepatic Helicobacter species as a facilitating factor in the development of Chlamydia trachomatis proctitis.

Gastrointestinal manifestations of chlamydial infection are frequent, yet not always recognised. One of the common entities is proctitis, especially prevalent amongst men who have sex with men (MSM). Likewise, some enterohepatic Helicobacter species have also been associated with proctitis, namely Helicobacter (H.) cinaedi and H. fennelliae. It is well established that Helicobacter species have general and specific mechanisms for innate immune evasion and suppression, and can affect intestinal homeostasis. Here it is proposed that their presence in the rectum might facilitate the development of Chlamydia trachomatis proctitis, where they could act as cofactors in initial infection and progression of the disease.

Effect of HIV and chlamydia infection on rectal inflammation and cytokine concentrations in men who have sex with men.

Asymptomatic Chlamydia trachomatis infections are common in HIV-infected men who have sex with men (MSM). Although C. trachomatis combined with HIV would be likely to enhance inflammation, the asymptomatic course suggests otherwise. We assessed local inflammation, mucosal damage, and cytokine concentrations in rectal mucosal fluid samples from patients with HIV (with or without the use of combination antiretroviral therapy [cART]) and with or without the presence of rectal C. trachomatis. Rectal swabs from 79 MSM (with and without C. trachomatis, HIV, and cART use) who reported a history of receptive anal sex were analyzed for neutrophil activation (measured by myeloperoxidase [MPO]), mucosal leakage (measured by albumin and alpha-2-macroglobulin), and proinflammatory and anti-inflammatory cytokines. C. trachomatis infection, HIV infection, and cART use in MSM had no differential effects on rectal neutrophilic inflammation and mucosal damage. Interleukin 8 (IL-8) was found to correlate with MPO, and MPO correlated with markers of mucosal damage. In HIV-negative participants, men with C. trachomatis infection had lower concentrations of monocyte chemotactic protein 1 (MCP-1), IL-1α, and IL-1 receptor antagonist (IL-1RA) than men without rectal C. trachomatis infection (P = 0.005, 0.007, and 0.07, respectively). We found no difference in anal cytokine concentrations in HIV-infected participants in relation to the presence of C. trachomatis infection or cART use. In participants with rectal C. trachomatis infection, those who were HIV negative had lower median concentrations of IL-8 and IL-1α than those with HIV (P = 0.05 and 0.06, respectively). The slope of the regression line between MPO and IL-8 was reduced in participants with rectal C. trachomatis infection. C. trachomatis dampens cytokine concentrations but not in HIV-infected patients. The extent of mucosal damage was comparable in all patient groups. The apparent reduced neutrophil response to IL-8 in HIV-infected patients with C. trachomatis infection is in accordance with its asymptomatic course.

Mucosal junctions: open doors to HPV and HIV infections?

Throughout adult life, new developmental commitment of adult stem cells causes reversible epithelial replacements in various mucosal surfaces, including the uterine cervix and the anal canal. Located at the squamocolumnar junctions, these metaplastic conversions are associated with chronic inflammation and deregulated expression of soluble and cell-membrane factors important for antiviral immune response. In this paper, we propose that these histological and immunological features increase the susceptibility of these metaplastic microenvironments to human papillomavirus and human immunodeficiency virus infections. Identification of the anatomical sites and cell populations within the anogenital tract, which is the site primary infected by these viruses, is crucial for the understanding of the pathogenesis of viral disease and development of antiviral strategies.