A Case Study: Incidental Finding of Human Intestinal Spirochetosis in Screening Colonoscopy.

Human intestinal spirochetosis (HIS) is a rare occurrence. We present an interesting case study on an asymptomatic over-60-year-old male who was incidentally discovered to have HIS following a colonoscopy that was conducted for his positive fecal occult blood test (FOBT). Histopathology of the colonic biopsy proved the presence of human intestinal spirochetosis; however, as he was asymptomatic, treatment was not initiated in his case. We discuss here the prevalence, presentation, diagnostic methods, and treatment of colonic HIS.

Identification of Terminal ßGlcNAc on Brachyspira Species in Human Intestinal Spirochetosis.

Human intestinal spirochetosis (HIS) is a colorectal bacterial infection caused by the Brachyspira species. Griffonia simplicifolia-II (GS-II) is a lectin specific to terminal α/ßGlcNAc residues. Here, we investigated terminal ßGlcNAc residues in the context of HIS infection using GS-II-horseradish peroxidase staining and HIK1083 immunostaining specific to terminal αGlcNAc residues. Fourteen of 15 HIS cases were GS-II-positive on the bacterial body. No cases showed HIK1083 positivity. The percentage of bacterial bodies staining positively for GS-II based on comparison with anti-Treponema immunostaining was ≤30% in seven cases, 30-70% in two, and >70% in six. Of 15 HIS cases analyzed, none were comorbid with tubular adenomas, and three were comorbid with sessile serrated lesions (SSLs). To determine the species of spirochete infected, the B. aalborgi-specific or B. pilosicoli-specific NADPH oxidase genes were amplified by PCR. After direct sequencing of the PCR products, all nine cases in which PCR products were observed were found to be infected with B. aalborgi alone. These results indicate that the HIS bacterial body, especially of B. aalborgi, is characterized by terminal ßGlcNAc and also indicate that terminal ßGlcNAc on the HIS bacterial body is associated with HIS preference for SSLs.

Human intestinal spirochetosis: an entity associated with sexual transmitted infections.

INTRODUCTION: Human intestinal spirochetosis (HIE) is a poorly studied clinical entity with variable clinical manifestations. However, in recent years it has gained special relevance because an increasing number of cases have been described in people living with HIV (PWH) and in patients with a history of sexually transmitted infections (STI) or immunosuppression. METHODS: Retrospective review of all HIE cases identified in a tertiary level hospital (Hospital Universitario la Paz, Madrid) between 2014 and 2021. RESULTS: 36 Cases of HIE were identified. Most cases corresponded to males (94%) with a median age of 45 years. 10 patients (29.4%) were PWH and 20 (56%) were men who had sex with men. Although the clinical manifestations were very heterogeneous, the most frequent was chronic diarrhea (47%), and up to 25% of the subjects had clinical proctitis. 39% percent of patients had been diagnosed with an STI in the previous two years, this characteristic being more frequent in PWH (90% vs. 28%; p < 0.01) than in patients without HIV infection. The STI most frequently associated with a diagnosis of HIE was syphilis (31%). CONCLUSION: HIE is frequently diagnosed with other STIs and affects mostly men who have sex with men, which supports that this entity could be considered as a new STI.

Human intestinal spirochetosis, histological finding associated with diarrhea with poor clinical evolution

Human intestinal spirochetosis was described by Harland and Lee in 1971, after observing colonization of the apical membrane of the intestinal mucosa by spirochetes. The clinical importance of these findings is not clear, since it is unknown whether the presence of these microorganisms is pathogenic or commensal. The clinical presentation is variable. It can be asymptomatic or manifest with abdominal pain, changes in intestinal rhythm and rectal bleeding. The prevalence of intestinal spirochaetosis is notably higher in developing countries than in developed countries, with the most likely route of transmission being fecal-oral, although sexual transmission has also been suggested as it is more prevalent in homosexual men. We present the case of a 42-year-old man, in treatment for 3 years with Tenofovir, with an HIV-positive partner, who went to the hospital for persistent diarrhea associated with eating a hamburger. (AU)

Intestinal Spirochetes Associated With Asymptomatic COVID-19 Infection.

A 60-year-old, human immunodeficiency virus (HIV)-negative, homosexual male presented to our colorectal clinic with abdominal pain for three weeks followed by persistent watery diarrhea refractory to loperamide. He had no history of recent travel, no known infectious contacts, and his last colonoscopy nine years prior was within normal limits. After one episode of hematochezia, computed tomography of the abdomen/pelvis was performed demonstrating colitis and coronavirus disease 2019 (COVID-19)-related changes to the lung bases. Testing confirmed COVID-19 infection which was self-limited. The initial workup for infectious colitis was negative. Colonoscopy revealed no evidence of gross colitis. Histopathology demonstrated microscopic colitis with spirochete colonization of the intestinal epithelium. A course of metronidazole led to the resolution of the patient's symptoms. Intestinal spirochetosis has been described as a rare source of colitis caused by the organism Brachyspira pilosicoli in an immunocompromised population (HIV-positive, organ transplant). It is associated with abdominal pain and refractory diarrhea. This report details the unique case of intestinal spirochetosis in an HIV-negative, COVID-19-positive patient with no other risk factors for immunosuppression. Further review is necessary to establish a true association; however, this case suggests that intestinal spirochetosis should be considered during the workup of chronic diarrhea (more than two weeks) in COVID-19-positive patients.

Human Intestinal Spirochetosis: A Rare Case of Intermittent Bloating and Hematochezia.

Human intestinal spirochetosis (HIS) is a condition where spirochetes, a group of spiral-shaped bacteria, attach to the apical membrane of the human colorectal epithelium. Although most findings of HIS are simply incidental discoveries found during screening colonoscopies, the ability to mimic the presentation of inflammatory bowel diseases should prompt consideration of this condition as part of a working differential diagnosis. Herein, we present the case of a 57-year-old bisexual, African American male with a medical history of Human Immunodeficiency Virus (HIV) on antiretroviral therapy (ART) with an undetectable viral load that presented for an elective, outpatient colonoscopy after experiencing four months of intermittent bloating and hematochezia. Histologic examination of colonic biopsies confirmed a diagnosis of HIS. The nonspecific clinical presentation in the setting of well-controlled HIV makes HIS a formidable diagnostic challenge that requires increased awareness.

Human Intestinal Spirochetosis Incompatible With Dysplastic Adenomatous Epithelium.

Human intestinal spirochetosis (HIS) refers to the colonization of spirochetal bacteria in the human intestinal tract. HIS caused by Brachyspira spp. has been recognized for decades, but their pathological and clinical significance is largely unclear. The coincidence of dysplasia in adenoma or adenocarcinoma and HIS is very rare, and whether spirochetes can colonize on dysplastic epithelium remains controversial. Here, we report a case that showed abrupt abolition of mucosal surface fringe formation on a tubular adenoma (TA) and increased cytoplasmic MUC1 expression in the dysplastic epithelial cells compared with adjacent nondysplastic colonocytes. The findings support the hypothesis that the epithelial colonization of spirochetes is significantly reduced by dysplasia likely due to loss of microvilli, and an increase of epithelial MUC1 expression might contribute to reduced spirochetal colonization in colonic mucosa.

Mucosal eosinophilic infiltration may be a characteristic of human intestinal spirochetosis.

BACKGROUND: Human intestinal spirochetosis (HIS) is an infectious disease of large intestines caused by Brachyspira species, and most HIS cases are asymptomatic or exhibit mild intestinal symptoms. The host reaction to HIS remains unclear, and we examined HIS-related mucosal inflammatory features histologically. METHODS: From the archival HIS cases in a single medical center, 24 endoscopically taken specimens from 14 HIS cases (male:female = 10:4; 28-73 yrs) were selected as not containing polypoid or neoplastic lesions. Stromal neutrophils, eosinophils, and mast cells, and intraepithelial neutrophils and eosinophils, (sNeu, sEo, sMast, iNeu, and iEo, respectively) were counted, and the presence or absence of lymphoid follicles/aggregates (LFs) was also examined. Association of the above inflammation parameters and spirochetal infection parameters (such as degrees of characteristic fringe distribution, of spirochetal cryptal invasion, and of spirochetal intraepithelial invasion) were also analysed. RESULTS: iNeu was observed in 29.2%, iEo in 58.3%, and LFs in 50.0% of the specimens. Maximal counts of sNeu, sEo, sMast, iNeu, and iEo averaged 8.4, 21.5, 6.0, 0.5 and 1.5, respectively. Strong correlation between the maximum counts of iNeu and iEo (p < 0.001, r = 0.81), and correlations between those of iEo and sNeu (p = 0.0012, r = 0.62) and between those of iEo and sEo (p = 0.026, r = 0.45) were observed. iNeu was influenced by fringe formation (p < 0.05) and spirochetal crypt involvement (p < 0.05). CONCLUSIONS: HIS was accompanied by inflammatory reactions, and among these, mucosal eosinophilic infiltration may be a central indicator and host reaction of HIS.

A Case of Human Intestinal Spirochetosis Diagnosed During Screening Colonoscopy.

Human intestinal spirochetosis (HIS) is a rare disease and mostly encountered incidentally during colorectal cancer screening colonoscopy. Risk factors include homosexuality and immunocompromised states. Patients are usually asymptomatic; however, chronic diarrhea and bloody stools have been reported in some cases. Diagnosis is usually confirmed by histopathology. A watch-and-see approach is usually acceptable, but successful treatment with Metronidazole has been reported in symptomatic cases. Its clinical significance remains questionable given that patients are mostly asymptomatic.

Human intestinal spirochetosis, a sexually transmissible infection? Review of six cases from two sexually transmitted infection centres in Barcelona.

Human intestinal spirochetosis (HIS) is a possible cause of chronic diarrhoea and affects mainly men who have sex with men (MSM) and people living with HIV. Diagnosis is based on colon biopsy, where spirochetes can be observed on the luminal surface, especially with the Warthin-Starry stain or similar silver stains. We conducted a retrospective descriptive study of all HIS cases diagnosed in two sexually transmitted infections (STI) centres in Barcelona from 2009 until 2018. The medical histories were reviewed to gather epidemiological, clinical, and diagnostic variables. Six patients were diagnosed with HIS. All the individuals were MSM, with a median age of 31.5 years (interquartile range [IQR] 29.5;49.25) and half of them were living with HIV. Five patients reported condomless anal intercourse and 4 patients had practised oro-anal sex previously. Concomitantly, two of them had rectal gonorrhoea, one had rectal Chlamydia trachomatis and none of them had syphilis. The predominant clinical symptom was diarrhoea (5 patients). All cases were diagnosed by a Warthin-Starry stain on a colon biopsy specimen, and mild inflammatory changes were found in 5 cases. Five patients were treated with metronidazole and one with benzathine penicillin G. Treatment was successful in all the patients. HIS should be considered in patients with chronic diarrhoea who report risky sexual practices and/or concomitant STI. HIS may also be sexually transmitted according to the context.

Histologic characteristics of human intestinal spirochetosis in operatively resected specimens.

Human intestinal spirochetosis (HIS), one of the zoonoses, is caused by colonization by Brachyspira species bacteria within the large intestine. Histologic diagnosis of HIS is usually established by finding "fringes" on the colonic surface epithelium in biopsy specimens. However, its histologic characteristics, especially beneath the colonic mucosa, have not been elucidated. The present study was designed to examine the histologic characteristics of HIS in operatively resected specimens. We reviewed operatively resected (colectomy or appendectomy) specimens obtained in six consecutive years at a single medical center. HIS was diagnosed histologically by finding "fringes". Immunohistochemical study using anti-Treponema pallidum antibody, which cross-reacts with Brachyspira, was additionally performed. A total of 848 (M:F = 477:371; median age, 59 years; 12-94 years) colectomy and/or appendectomy cases were examined, and the seven cases (0.8%) diagnosed as having HIS were all male (1.5% of male cases). Four HIS cases (0.8% of 508 colectomy cases (1.4% of 285 male-cases)) were colectomy cases with cancers, and the other three (0.9% of 340 appendectomy cases (1.6% of 192 male-cases)) were appendectomy cases for acute appendicitis. Our study revealed (1) a heterogeneous distribution of diagnostically important "fringes" within the large intestine, (2) an ileal presence of Brachyspira, (3) superficial location of HIS-related findings among anatomical wall layers, and (4) the presence of Brachyspira or its derivatives within macrophages in the lamina propria and immune apparatus (lymphoid follicles in superficial wall structures (lamina propria or submucosa) and lymph nodes). Investigation using operatively resected specimens might help elucidate the characteristics of HIS. Brachyspira may have immunogenicity in humans.

Human intestinal spirochetosis mimicking ulcerative colitis.

Human intestinal spirochetosis (HIS) is a colorectal infection caused by the Brachyspira species of intestinal spirochetes, whose pathogenicity in humans remains unclear owing to the lack of or mild symptoms. We monitored the 5-year clinical course of a woman diagnosed with HIS in whom ulcerative colitis (UC) had been suspected. Following a positive fecal occult blood test, she underwent a colonoscopic examination at a local clinic where she was diagnosed with "right-sided" UC concomitant with incidentally detected HIS, and was referred to our hospital. Colonoscopic, histopathological, and cytological examination revealed localized erosive colitis in the ascending and the right transverse colon concomitant with HIS resembling skip lesions of UC. Initially, we chose the wait-and-watch approach; however, she gradually developed bloody diarrhea. Metronidazole improved her abdominal symptoms, as well as her colonoscopic and histopathological findings, suggesting that HIS was responsible for her colorectal inflammation. This case reveals (1) a possible pro-inflammatory role of HIS, (2) difficulties in diagnosing HIS in chronic proctocolitis, and (3) a possible inclusion of some HIS cases in "UC". HIS could mimic UC and might be included in differential diagnoses for UC. Antibiotic administration is necessary following the detection of HIS, particularly in patients demonstrating an atypical presentation of UC.

Human intestinal spirochetosis in Japanese patients aged less than 20 years: Histological analysis of colorectal biopsy and surgical specimens obtained from 479 patients.

Human intestinal spirochetosis (HIS) is a condition in which spirochetes attach to and colonize the colorectal epithelium. To our knowledge, no comprehensive studies of HIS in young patient have been published in a developed country. This study aimed to determine the incidence and clinicopathological manifestations of HIS in Japanese patients aged less than 20 years. We retrospectively reviewed 3605 biopsy and 92 surgical specimens obtained from 479 patients admitted to Shinshu University Hospital between 1997 and 2014. All slides were reviewed independently by two pathologists to confirm the histological presence of spirochetes. Among 387 patients who underwent biopsy, the most common pathologic diagnosis was ulcerative colitis (12.6%, n = 49). Additionally, about half of the biopsy specimens showed non-specific, mildly inflamed mucosa (50.6%, n = 196); only one of these cases was HIS. On the other hand, among the surgical specimens, we found no cases of HIS. We concluded that the incidence of HIS in Japanese young patients was 0.2% (1/479 cases). The incidence of HIS in Japanese young patients was very low, and one HIS case was associated with colitis with abdominal pain.

Distribution and phylogeny of Brachyspira spp. in human intestinal spirochetosis revealed by FISH and 16S rRNA-gene analysis.

During six years as German National Consultant Laboratory for Spirochetes we investigated 149 intestinal biopsies from 91 patients, which were histopathologically diagnosed with human intestinal spirochetosis (HIS), using fluorescence in situ hybridization (FISH) combined with 16S rRNA gene PCR and sequencing. Aim of this study was to complement histopathological findings with FISH and PCR for definite diagnosis and species identification of the causative pathogens. HIS is characterized by colonization of the colonic mucosa of the human distal intestinal tract by Brachyspira spp. Microbiological diagnosis of HIS is not performed, because of the fastidious nature and slow growth of Brachyspira spp. in culture. In clinical practice, diagnosis of HIS relies solely on histopathology without differentiation of the spirochetes. We used a previously described FISH probe to detect and identify Brachyspira spp. in histological gut biopsies. FISH allowed rapid visualization and identification of Brachyspira spp. in 77 patients. In most cases, the bright FISH signal already allowed rapid localization of Brachyspira spp. at 400× magnification. By sequencing, 53 cases could be assigned to the B. aalborgi lineage including "B. ibaraki" and "B. hominis", and 23 cases to B. pilosicoli. One case showed mixed colonization. The cases reported here reaffirm all major HIS Brachyspira spp. clusters already described. However, the phylogenetic diversity seems to be even greater than previously reported. In 14 cases, we could not confirm HIS by either FISH or PCR, but found colonization of the epithelium by rods and cocci, indicating misdiagnosis by histopathology. FISH in combination with molecular identification by 16S rRNA gene sequencing has proved to be a valuable addition to histopathology. It provides definite diagnosis of HIS and allows insights into phylogeny and distribution of Brachyspira spp. HIS should be considered as a differential diagnosis in diarrhea of unknown origin, particularly in patients from risk groups (e.g. patients with colonic adenomas, inflammatory polyps, inflammatory bowel disease or HIV infection and in men who have sex with men).

Immunohistochemical study of mucins in human intestinal spirochetosis.

Most patients with human intestinal spirochetosis (HIS; a colorectal bacterial infection caused by Brachyspira species) seem asymptomatic, and its pathogenicity remains unclear. Recently, alterations in mucin expression were reported in animal Brachyspira infection. The present question was "Is mucin expression altered in HIS?" Using antibodies for MUCs 1, 2, 4, 5AC, and 6, we immunohistochemically compared 215 specimens from 83 histology-confirmed HIS cases with 106 specimens from 26 non-HIS cases. Positive staining (which included even focal positive staining) was rated "high (+)" or "low (+)." Results were analyzed for 4 categories of lesions, and associations between MUC expression and spirochetal presence were also analyzed. In the "specimens without polyps or adenocarcinoma" category, high (+) MUC2 positivity was more frequent in HIS than in control. In the hyperplasia/serrated polyp category, in HIS (versus control), the MUC5AC positivity rate was lower, whereas high (+) MUC4 positivity was more frequent. In the conventional adenoma category, in HIS (versus control), the MUC1 positivity rate was lower, whereas both high (+) MUC2 positivity and high (+) MUC5AC positivity were less frequent. In the adenocarcinoma category, high (+) MUC2 positivity was more frequent in HIS than in control. Among the above mucins, only MUC1 positivity was significantly associated with an absence of the so-called fringe formation, an absence of spiral organisms within mucus, and an absence of strong immunopositive materials within the epithelial layer and within the subepithelial layer. The results suggest that Brachyspira infection or a related change in the microbiome may alter the large intestine mucin expression profile in humans.

Immunohistochemical detection of human intestinal spirochetosis.

Human intestinal spirochetosis (HIS) is a colorectal infection by Brachyspira species of spiral bacteria. Immunohistochemical cross-reaction to an antibody for Treponema pallidum aids its histologic diagnosis. This study's aim was to analyze the immunohistochemical characteristics of HIS. In this analysis, on 223 specimens from 83 HIS cases, we focused on so-called fringe formation (a histologic hallmark of HIS), spiral organisms within mucus or within crypts, and strong immunopositive materials in the mucosa, together with their location and the types of lesions. Fringe formation was found in 81.6% of all specimens and spiral organisms within mucus or within crypts in 97.3% and 57.0%, respectively. Strong immunopositive materials were observed in the surface epithelial layer in 87.9%, in the subepithelial layer in 94.6%, and in deeper mucosa in 2.2% of all specimens. The positive rates in conventional adenomas (24.0%, n = 146) and hyperplastic nodules (100%, n = 17) were each different from that found in inflammation (70.8%, n = 24), and spiral organisms were seen more frequently in the right-side large intestine than in the left (within mucus, 100%, n = 104 versus 95.0%, n = 119; within crypts, 65.4%, n = 104 versus 49.6%, n = 119). Thus, immunohistochemistry was effective not only in supporting the diagnosis of HIS but also in highlighting spiral organisms within mucus or crypts that were invisible in routine histology. Possibly, these spiral organisms may spread throughout the entire large intestine, although there is a potential problem with antibody specificity.

Human intestinal spirochetosis is significantly associated with sessile serrated adenomas/polyps.

It remains unclear whether or not human intestinal spirochetosis (HIS) has any associated symptoms or lesions. In this study, we assessed the prevalence of HIS in sessile serrated adenomas/polyps (SSA/Ps) and their possible association. Following identification of early cecal cancer with SSA/P accompanied by a colonization of HIS, we went on to conduct a retrospective case-control study using endoscopically resected SSA/P specimens to examine the frequency of HIS infection in SSA/Ps. Nineteen SSA/P cases and 172 controls were obtained. The rate of HIS infection was significantly higher at 52.6% (10/19) in the SSA/P cases compared to the controls at 8.1% (14/172). Our SSA/P series were associated with a remarkably higher rate of HIS than controls or than previously reported. This is the first report to provide evidence for potential association between HIS and SSA/Ps.

Human intestinal spirochetosis in an immunocompromised host: evaluation of eradication therapy by endoscopy, histopathology and bacteriology.

Human intestinal spirochetosis (HIS) is a colorectal infectious disease caused by Brachyspira species. We describe HIS in an immunocompromised, 62-year-old Japanese man who presented at Jichi Medical University Hospital with symptoms of diarrhea and bloody stool. He had rheumatoid arthritis that had been treated with immunosuppressive drugs for 10 years. Colonoscopy revealed multiple erythematous spots in the cecum and colon. A histopathological examination identified intestinal colonization by spirochetes, and Brachyspira pilosicoli was isolated from biopsy specimens, indicating a diagnosis of HIS. Metronidazole eradicated the spirochetes, the intestinal mucosa recovered to normal, and the clinical symptoms disappeared. This case suggests that it is important to keep in mind HIS in the differential diagnosis of immunocompromised patients with chronic diarrhea and bloody stool.

Human intestinal spirochetosis--a review.

Human intestinal spirochetosis (IS) is a condition defined histologically by the presence of spirochetal microorganisms attached to the apical cell membrane of the colorectal epithelium. Intestinal spirochetes comprise a heterogeneous group of bacteria. In humans, Brachyspira aalborgi and Brachyspira pilosicoli predominate. Prevalence rates of IS are low where living standards are high, in contrast to poorly developed areas where IS is common. Homosexuals and HIV-infected individuals are at high risk of being colonized. Clinical significance in individual cases has remained unclear up to now. A review of the literature assumes that invasion of spirochetes beyond the surface epithelium may be associated with gastrointestinal symptoms which respond to antibiotic treatment (metronidazole), whereas individuals lacking this feature may be mostly asymptomatic. Of unknown reason, homosexual and HIV-positive men as well as children are more likely to be symptomatic irrespective of invasion. Rare cases of spirochetemia and multiple organ failure have been reported in critically ill patients with IS.