Spirochetosis Research Articles

Human intestinal spirochetosis, irritable bowel syndrome, and colonic polyps: A systematic review and meta-analysis.

Human colonic spirochetosis (CS) is usually due to Brachyspira pilosicoli or Brachyspira aalborgi infection. While traditionally considered to be commensal bacteria, there are scattered case reports and case series of gastrointestinal (GI) symptoms in CS and reports of colonic polyps with adherent spirochetes. We performed a systematic review and meta‐analysis investigating the association between CS and GI symptoms and conditions including the irritable bowel syndrome (IBS) and colonic polyps. Following PRISMA 2020 guidelines, a systematic search of Medline, CINAHL, EMBASE, and Web of Science was performed using specific keywords for CS and GI disease. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random‐effects model. Of 75 studies identified in the search, 8 case–control studies met the inclusion criteria for meta‐analysis and 67 case series studies met the inclusion criteria for pooled prevalence analysis. CS was significantly associated with diarrhea (n = 141/127, cases/controls, OR: 4.19, 95% CI: 1.72–10.21, P = 0.002) and abdominal pain (n = 64/65, OR: 3.66, 95% CI: 1.43–9.35, P = 0.007). CS cases were significantly more likely to have Rome III‐diagnosed IBS (n = 79/48, OR: 3.84, 95% CI: 1.44–10.20, P = 0.007), but not colonic polyps (n = 127/843, OR: 8.78, 95% CI: 0.75–103.36, P = 0.084). In conclusion, we found evidence of associations between CS and both diarrhea and IBS, but not colonic polyps. CS is likely underestimated due to suboptimal diagnostic methods and may be an overlooked risk factor for a subset of IBS patients with diarrhea.

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.

A201 A CASE OF SYPHILIS MASQUARADING AS CROHN’S DISEASE

BackgroundIt is important for gastroenterologists to keep syphilis on their differential. We present a case of rectal syphilis initially misdiagnosed as Crohn’s disease with commensal intestinal spirochetosis.AimsThis case highlights how rectal syphilis can present with endoscopic and clinical findings consistent with refractory inflammatory bowel disease.MethodsCase report and literature review.ResultsA 58 healthy male was referred for flexible sigmoidoscopy after having increased frequency of bowel movements, up to 10 per day, with mucous secretions at times mixed with blood and a 35lbs weight loss. He complained of urgency, tenesmus and intermittent incontinence. Endoscopy showed evidence of proctitis in the distal 10cm of the rectum with ulceration, edema and friability with biopsies showing moderately active colitis, compatible with ulcerative colitis.5-ASA suppositories and subseqent oral prednisone had no effect. A colonoscopy 3 months later again showed proctitis and ulceration. Biopsies at this time showed moderately active proctitis with chronic architectural distortion and intestinal spirochetosis identified on Warthin-Starry stain in the right colon and rectum. Given the patient was immunocompetent he was diagnosed with inflammatory bowel disease and trialed on oral and rectal 5-ASA.Four months later flexible sigmoidoscopy showed extensive distal rectal ulceration, biopsies positive for chronic proctitis and intestinal spirochetosis. Given no response to 5-ASA the patient was started on infliximab with a slight improvement but incomplete resolution of his symptoms. Repeat endoscopy showed continued rectal ulceration.Incidentally, the patient had a same sex sexual encounter and subsequently tested positive for syphilis with positive T. pallidum EIA and an RPR of 1:8. He received benzathine penicillin G 2.4 million units intramuscularly.After treatment with penicillin, the patient’s symptoms improved with no further hematochezia and decreased frequency. Flexible sigmoidoscopy showed normal mucosa with no evidence of ulceration indicating the initial proctitis and ulceration was secondary to infection by T. pallidum.ConclusionsSyphilis, known as the “Great imitator,” is on the rise in Canada, with cases of infectious syphilis increasing more than 259.5% over the past decade. Rectal syphilis is often misdiagnosed as it can present with variable symptoms including puritis, tenesmus, urgency of defecation and anal discharge that may be purulent, mucoid or bloody. Endoscopic findings include non-specific proctitis, masses, ulceration and pseudotumors. Diagnosis is made with serology as pathology cannot differentiate between commensal intestinal spirochetosis and T. pallidum.Given the diversity of presentations and rise in incidence, gastroenterologists need to ensure they take a thorough sexual history and keep syphilis on their differential when encountering this common clinical scenario.Funding AgenciesNone

Erosive acute colitis associated with intestinal spirochetosis

BackgroundAlthough usually believed to be harmless, intestinal spirochetosis may active erosive colitis associated with intestinal spirochetosis that may mimic idiopathic chronic inflammatory bowel disease. Case presentation. A 49-year-old homosexual male patient sought medical assistance due to asthenia, rectal bleeding, tenesmus, and diarrhea for one month. He had been using corticosteroids for nine months to treat sciatic nerve pain. Colonoscopy showed rectum and distal sigmoid with diffuse erythema with many surface erosions. Rectal biopsy showed inflammatory changes including chronic changes such as architectural distortion and basal plasmacytosis, and active inflammation including crypt microabscesses. In all large bowel sample, dense colonization of intestinal spirochetosis was observed. Patient also had a positive PCR testing for Chlamydia trachomatis. The patient was treated with metronidazole for 14 days, ciprofloxacin for 14 days and azithromycin (single dose). Symptoms improved and the patient is asymptomatic after two months of follow-up.ConclusionIn some high-risk groups, intestinal spirochetosis may cause colonic manifestations with overlapping features with intestinal bowel diseases. Awareness of this association is importance since proper antibiotic therapy against Brachyspira (metronidazole) is highly effective. Coinfection with other sexually transmitted infections is common and proper treatment is required.

Intestinal Spirochaetosis-A case series from the developing world

Spirochaetes comprise a heterogenous group of gram negative, motile, spiral shaped bacteria. Some of these pathogens are known to cause numerous human diseases such as Lyme disease, relapsing fever, syphilis and leptospirosis. However, intestinal spirochetosis is a rare condition. Patients frequently present with long-term complaints of loose stools, abdominal pain and weight loss and rectal bleeding. Hence to establish a diagnosis an endoscopy with biopsy is required. In this article, we describe four such cases, having different ages and socio- economic background, successfully treated with a short course of metronidazole.

Mucosal eosinophilic infiltration may be a characteristic of human intestinal spirochetosis

BackgroundHuman 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.MethodsFrom 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.ResultsiNeu 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).ConclusionsHIS was accompanied by inflammatory reactions, and among these, mucosal eosinophilic infiltration may be a central indicator and host reaction of HIS.

Intestinal Spirochetosis in an HIV-positive Patient.

Intestinal spirochetosis is associated with chronic diarrhoea and often with normal colonoscopy.This infection should be included in the differential diagnosis of HIV patients with digestive symptomatology in the absence of other more frequent causes.

Identification of Brachyspira spp. in the cecum of broiler chickens using histology and in situ diagnostic assays

The genus Brachyspira corresponds to the group of bacteria formerly classified into the genus Serpulina and includes several commensal and pathogenic intestinal spirochetes that affect pigs, poultry, and other animal species, including humans. In birds, some pathogenic species of this genus causes a condition known as avian intestinal spirochetosis, which remains underdiagnosed, thereby causing serious economic losses. Brachyspira is a fastidious organism that necessitates the employment of fast and efficient identification techniques. The aim of this study was to identify Brachyspira spp. using histology, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in formalin-fixed paraffin embedded (FFPE) tissue samples from the cecum of commercial poultry. Samples were collected from 129 birds aged between 35 and 45 days from commercial broiler farms. For evaluation, routine histology processing (H&amp;E) and the histochemical technique, periodic acid–Schiff (PAS) were done. Additionally, FFPE tissue samples were evaluated for FISH and IHC. The histological lesions were analyzed and graded after H&amp;E staining, and the goblet cells were counted and compared using PAS staining with the positive and negative samples obtained through FISH and IHC. For FISH, probes labeled with Brachyspira spp., B. pilosicoli, B. hyodysenteriae, and B. intermedia were used, whereas rabbit polyclonal antibody specific for Brachyspira spp. was used for IHC. Of 129 samples, 82 were positive with IHC and 86 were positive with FISH. The samples positive for the genus Brachyspira in the FISH technique were tested for B. pilosicoli, B. hyodysenteriae, and B. intermedia in which 56 were positive for B. pilosicoli, 75 for B. hyodysenteriae and 80 for B. intermedia. There was an increase in goblet cells in the samples positive for FISH and IHC. The techniques used were effective and gave corresponding results, thus serving as a fast and efficient tool for diagnosis.

2021 European Guideline on the management of proctitis, proctocolitis and enteritis caused by sexually transmissible pathogens.

This guideline intents to offer guidance on the diagnosis and management of patients with gastrointestinal symptoms and a suspected sexually transmitted cause. Proctitis is defined as an inflammatory syndrome of the anal canal and/or the rectum. Infectious proctitis can be sexually transmitted via genital-anal mucosal contact, but some also via digital contact and toys. Neisseria gonorrhoeae, Chlamydia trachomatis (including lymphogranuloma venereum), Treponema pallidum and herpes simplex virus are the most common sexually transmitted anorectal pathogens. Shigellosis can be transferred via oral-anal contact and may lead to proctocolitis or enteritis. Although most studies on these infections have concentrated on men who have sex with men (MSM), women having anal intercourse may also be at risk. A presumptive clinical diagnosis of proctitis can be made when there are symptoms and signs, and a definitive diagnosis when the results of laboratory tests are available. The symptoms of proctitis include anorectal itching, pain, tenesmus, bleeding, constipation and discharge in and around the anal canal. The majority of rectal chlamydia and gonococcal infections are asymptomatic and can only be detected by laboratory tests. Therefore, especially when there is a history of receptive anal contact, exclusion of anorectal infections is generally indicated as part of standard screening for sexually transmitted infections (STIs). Condom use does not guarantee protection from STIs, which are often spread without penile penetration. New in this updated guideline is: (i) lymphogranuloma venereum proctitis is increasingly found in HIV-negative MSM, (ii) anorectal Mycoplasma genitalium infection should be considered in patients with symptomatic proctitis after exclusion of other common causations such N.gonorrhoeae, C.trachomatis, syphilis and herpes, (iii) intestinal spirochetosis incidentally found in colonic biopsies should not be confused with syphilis, and (iv) traumatic causes of proctitis should be considered in sexually active patients.

A survey on the occurrence of Brachyspira pilosicoli and Brachyspira hyodysenteriae in growing-finishing pigs.

Background: The major pathogenic intestinal spirochetes affecting pigs during the growing- finishing stage of production include Brachyspira hyodysenteriae and Brachyspira pilosicoli. The aim of this study was to assess the current occurrence of B. hyodysenteriae and B. pilosicoli in Polish pig herds. Moreover, associations between the presence of diarrhea or other intestinal pathogens and occurrence of B. hyodysenteriae and B. pilosicoli in pigs were investigated. Methods: Between January 2017 and August 2019, a total of 401 samples of pig feces from 95 different herds were submitted to the National Veterinary Research Institute of Poland. These samples were obtained from pigs older than 7 weeks. All the received fecal samples were examined for the presence of B. hyodysenteriae, B. pilosicoli and Lawsonia intracellularis by real-time PCR. Results: B. pilosicoli was detected in 4.5% (95% CI, 2.5-7.0%) (18/401) of pig fecal samples. At the herd level 13.7% (95% CI, 7.5-22.3%) (13/95) of herds were positive for B. pilosicoli. B. hyodysenteriae was detected in 7.0% (95% CI, 4.7-9.9%) (28/401) of pig fecal samples and 18.9% (95% CI, 11.6-28.3%) (18/95) of pig herds were positive. Out of 18 B. pilosicoli positive samples, this pathogen was detected alone in 5 samples; simultaneously with L. intracellularis in 9 samples; simultaneously with B. hyodysenteriae in 1 sample and in 3 samples was detected simultaneously with both of these bacteria. The presence of B. hyodysenteriae in fecal samples was associated with the presence of diarrhea in pigs. Conclusions: This study confirmed that B. pilosicoli infections occur in Polish pig herds, but the prevalence is at a low level and the presence of B. pilosicoli is not associated with the development of diarrhea in pigs. B. hyodysenteriae is still a common cause of diarrhea among pigs from Polish herds.

Asymptomatic Intestinal Spirochetosis Found Incidentally in Endoscopic Specimens

Asymptomatic Intestinal Spirochetosis Found Incidentally in Endoscopic Specimens

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.

S0144 Risk Factors for Intestinal Spirochetosis in an Urban Community

INTRODUCTION: Human intestinal spirochetosis can be a cause of diarrhea in immunocompromised patients and has uncertain significance in patients who are immunocompetent. The exact prevalence of the disease is unknown, but reports indicate that it may range from 0.4% to 12%. There have been increasing reports of asymptomatic individuals with colon biopsies revealing spirochetosis. The aim of this study is to identify risk factors associated with intestinal spirochetosis in an urban university medical center. METHODS: A retrospective, IRB exempt, chart review between January 2016 and December 2019 was conducted to identify colonic biopsies with intestinal spirochetosis. Patient age, gender, self-identified race, sexual practices, HIV status, symptoms and socioeconomic status (based upon insurance) were obtained. A confidential database was created. Statistical analysis was conducted using Fisher exact test with significance set at P < 0.05. RESULTS: Twenty-one cases of biopsy-confirmed intestinal spirochetosis were identified in patients with a mean age of 48. There was 1 (4.8%) female and 20 (95.2%) males, of whom 13 (62%) were men who have sex with men (MSM). Nine (43%) were HIV positive, 6 (29%) were HIV negative and 6 (29%) had unknown HIV status. Nine (43%) were White, 9 (43%) were Black, and 3 (14%) were Hispanic. Eleven patients (52%) had private insurance, 8 (38%) had Medicaid and 2 (10%) had Medicare. Eight (38%) were symptomatic. Men had significantly more spirochetosis than women (P = 0.0001). Individuals who were HIV positive were not more likely to be symptomatic than those who were HIV negative or those who had unknown HIV status (P = 0.67). There was no significant difference in the presence of intestinal spirochetosis based race (P = 0.08) or insurance status (P = 1.000). CONCLUSION: This study characterized 21 cases of human intestinal spirochetosis in a diverse urban, U.S. population. Consistent with previously published data, the majority of cases were MSM, among which a large proportion of individuals were HIV positive. Differing from previous reports, this study revealed that individuals who were HIV positive were no more likely to have diarrhea than those who were HIV negative. While this study is limited based upon size and single institutional design, it offers a foundation for further research. Additional studies are necessary to understand risk factors, prevalence and presentation of intestinal spirochetosis.

S1749 Human Intestinal Spirochetosis: An Atypical Cause of Symptomatic Colonic Ulceration

INTRODUCTION: This case demonstrates an atypical presentation of intestinal spirochetosis in a patient with HIV on anti-retroviral therapy with adequate viral suppression. CASE DESCRIPTION/METHODS: A 56-year-old male presented with one day of hematochezia and abdominal cramping. He had a past medical history of HIV on Highly Active Antiretroviral Therapy with recent undetectable viral load and CD4 count of 1225. On initial assessment, he was tachycardic with frank blood on rectal examination. Hemoglobin was 11.8 with a baseline of 14.7. Computed Tomography scan of the abdomen and pelvis was significant for contrast extravasation in the cecum consistent with active gastrointestinal bleed. His hemoglobin further downtrended to 9.4, but he remained hemodynamically stable. Colonoscopy revealed a solitary twenty mm ulcer in the cecum without active bleeding. Biopsy obtained from the ulcer edge demonstrated intestinal spirochetosis (Warthin-Starry stain positive) and focal acute colitis with lamina propria hemorrhage. Patient remained clinically stable without further episodes of hematochezia and was discharged before biopsies resulted. Unfortunately, he was lost to follow-up. DISCUSSION: Human intestinal spirochetosis is rare in developed countries but when present, they are often found in homosexual males and those with HIV. Stool colonization rates in homosexual men in the US have ranged between 20.6 and 62.5%. It is most commonly caused by Brachyspira aalborgi or Brachyspira pilosicoli. Patients are often asymptomatic but can present with abdominal pain and watery diarrhea. Endoscopic findings are usually non-specific since mucosa may be normal, polypoid, or mildly erythematous. There are only case reports of colonic ulceration. Diagnosis is made by histology with hematoxylin-eosin and Warthin-Starry silver stains which demonstrate spirochetal adhesion along the border of the intercryptal epithelial layer. Treatment is reserved for immunocompromised and symptomatic patients and consists of metronidazole for 10 days with resolution of symptoms. Complete mucosal healing has been observed for those who opt for repeat endoscopy. Our patient is unique since he had sudden large-volume hematochezia without diarrhea and a rather discrete endoscopic finding despite viral suppression and a robust CD4 count. Therefore, clinical suspicion for intestinal spirochetosis should be moderately high in patients with these specific risk factors.Figure 1.: Clean-based cecal ulcer.Figure 2.: Warthin-Starry silver stain of cecal ulcer edge biopsy highlighting spirochetes on the surface epithelium.

S3376 Human Intestinal Spirochetosis: A Rare Cause of Chronic Diarrhea in a Patient With HIV and Ulcerative Colitis

S3376 Human Intestinal Spirochetosis: A Rare Cause of Chronic Diarrhea in a Patient With HIV and Ulcerative Colitis

S1832 Intestinal Spirochetosis in an Immunocompetent Patient Carrying a Diagnosis of Irritable Bowel Syndrome With Diarrhea (IBS-D)

S1832 Intestinal Spirochetosis in an Immunocompetent Patient Carrying a Diagnosis of Irritable Bowel Syndrome With Diarrhea (IBS-D)

Clinical significance of human intestinal spirochetosis

Clinical significance of human intestinal spirochetosis

Intestinal Spirochetes in Cancer Patients

Abstract The clinical significance of human intestinal spirochetosis is a debated topic, with possible links to various gastrointestinal symptoms such as diarrhea and hematochezia. The most commonly associated organisms in humans involve Brachyspira aalborgi and Brachyspira pilosicoli. However, the presence of spirochetes within the colorectal epithelium does not always suggest pathogenicity, and treatment does not always lead to symptom improvement. Men who have sex with men and patients infected with the HIV have been considered at higher risk of colonization and subsequently becoming symptomatic, possibly related to an underlying immunosuppressed state. We present a series of 3 case reports of human intestinal spirochetosis in immunocompromised cancer patients at the Moffitt Cancer Center and Research Institute. The aim of this study is to increase awareness of this entity in immunocompromised cancer patients and non–HIV-positive immunosuppressed patients, particularly when presenting with gastrointestinal symptoms of unclear etiology.

A survey on the occurrence of Brachyspira pilosicoli and Brachyspira hyodysenteriae in growing-finishing pigs

Background: The major pathogenic intestinal spirochetes affecting pigs during the growing- finishing stage of production include Brachyspira hyodysenteriae and Brachyspira pilosicoli. The aim of this study was to assess the current occurrence of B. hyodysenteriae and B. pilosicoli in Polish pig herds. Moreover, associations between the presence of diarrhea or other intestinal pathogens and occurrence of B. hyodysenteriae and B. pilosicoli in pigs were investigated. Methods: Between January 2017 and August 2019, a total of 401 samples of pig feces from 95 different herds were submitted to the National Veterinary Research Institute of Poland. These samples were obtained from pigs older than 7 weeks. All the received fecal samples were examined for the presence of B. hyodysenteriae, B. pilosicoli and Lawsonia intracellularis by real-time PCR. Results: B. pilosicoli was detected in 4.5% (95% CI, 2.5–7.0%) (18/401) of pig fecal samples. At the herd level 13.7% (95% CI, 7.5–22.3%) (13/95) of herds were positive for B. pilosicoli. B. hyodysenteriae was detected in 7.0% (95% CI, 4.7–9.9%) (28/401) of pig fecal samples and 18.9% (95% CI, 11.6–28.3%) (18/95) of pig herds were positive. Out of 18 B. pilosicoli positive samples, this pathogen was detected alone in 5 samples; simultaneously with L. intracellularis in 9 samples; simultaneously with B. hyodysenteriae in 1 sample and in 3 samples was detected simultaneously with both of these bacteria. The presence of B. hyodysenteriae in fecal samples was associated with the presence of diarrhea in pigs. Conclusions: This study confirmed that B. pilosicoli infections occur in Polish pig herds, but the prevalence is at a low level and the presence of B. pilosicoli is not associated with the development of diarrhea in pigs. B. hyodysenteriae is still a common cause of diarrhea among pigs from Polish herds.

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, 59years; 12-94years) 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.