Spirochetosis Research Articles

Intestinal spirochetosis: An unusual cause of postantibiotic diarrhea.

(A) A blue fringe along the surface epithelium of the colonic mucosa on hematoxylin-eosin staining, a characteristic histology of intestinal spirochetosis. (B) Numerous spirochetes highlighted on Warthin-Starry silver staining.

Survival of pathogenic intestinal Spirochetes kept in pure cultures and in pig feces at four different temperatures

Porcine colonic spirochetosis (PCS) caused by Brachyspira pilosicoli has been identified as a contributing cause of diarrhea and reduced performance of growing pigs in all major swine producing countries. The current view that transmission of PCS occurs through contamination of the environment by acutely or persistently infected pigs is based on the assumption that the spirochetes remain viable in the environment. The purpose of this study was to compare the viability of Brachyspira pilosicoli kept in pure culture or mixed with feces at four different temperatures over time with that of Brachyspira hyodysenteriae . The results of the present study indicated that Brachyspira pilosicoli survived significantly longer than Brachyspira hyodysenteriae in pure cultures held at 24°C and 37°C, and at all temperatures in spiked fecal materials. Pure cultures of Brachyspira pilosicoli survived at least 63 days at -70°C, seven days at 4°C, 14 to 28 days at 24°C and seven to 28 days at 37°C. There was significant differences in the survival of the 2 species of spirochetes when mixed with feces. At -70°C, Brachyspira pilosicoli and Brachyspira hyodysenteriae survived respectively an average of 21 and 3 days, and at 4°C 12,25 and 4,25 days. Viability was reduced to one to seven days at 24°C and one to three days at 37°C for Brachyspira pilosicoli and Brachyspira hyodysenteriae . Information on the survival of Brachyspira pilosicoli outside the pig’s body provides a basis to improve strategies for PCS control.

Antimicrobial Susceptibility Patterns of Brachyspira Species Isolated in Taiwan.

Some members of the Brachyspira genus cause diseases such as swine dysentery (SD) and porcine intestinal (or colonic) spirochetosis. Severe economic losses are caused by decreased feed intake and increased feed conversion ratio, as well as costs associated with treatment and death. A loss of clinical efficacy of some antimicrobial agents authorized for treating SD has been observed in many countries. The aim of this study was to analyze the antimicrobial susceptibility of Brachyspira isolated from Taiwan and to investigate the mechanism of decreased susceptibility to macrolides. A total of 55 Brachyspira isolates obtained from the grower-finisher period were evaluated in this study. These isolates included B. hyodysenteriae (n = 37), B. murdochii (n = 11), B. pilosicoli (n = 5), B. intermedia (n = 1), and B. innocens (n = 1). Antimicrobial susceptibility testing was performed to examine 12 selected antimicrobial agents. The results showed that the 50% and 90% minimum inhibitory concentration (MIC) values of the tested macrolides were all >256 μg/ml. The MIC50 of lincomycin, tiamulin, carbadox, olaquindox, ampicillin, amoxicillin, doxycycline, oxytetracycline, and gentamicin were 32, 1, ≤0.125, ≤0.125, 0.5, 0.25, 2, 2, and 2 μg/ml. The genetic basis of the decreased susceptibility to tylosin and lincomycin in Brachyspira spp. was investigated and the results showed a possible connection to the mutations at position A2058 and G2032 of the 23S rRNA gene. These findings demonstrated that, in Taiwan, there may be a decrease in susceptibility of Brachyspira spp. to antimicrobials commonly used for the treatment of SD.

Differentiation of Brachyspira spp. isolated from laying hens using PCR-based methods and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Avian intestinal spirochetosis (AIS), an important but neglected disease in laying hens, is caused by Brachyspira pilosicoli, B. intermedia, and B. alvinipulli. Poultry are also frequently colonized by putatively nonpathogenic species such as B. murdochii and B. innocens. We evaluated the differentiation of Brachyspira species by 3 methods: sequencing of the reduced nicotinamide adenine dinucleotide (NADH) oxidase gene ( nox), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and a new multiplex (m)PCR targeting genes such as the tryptophanase A gene ( tnaA) and the p-aminobenzoyl-glutamate hydrolase subunit B gene ( abgB). Sequencing of 414 bp of the nox PCR amplification products generated from 41 pure cultures of avian Brachyspira isolates allowed presumptive species identification in 33 isolates with at least 99% identity in basic local alignment search tool analysis, including B. pilosicoli, B. intermedia, B. murdochii, B. innocens, and " B. pulli". MALDI-TOF MS analysis was found to be a reliable tool for differentiation after extension of the manufacturer's database. In the mPCR, all isolates identified as B. pilosicoli and B. intermedia were positive for abgB and tnaA, respectively. The mPCR might be very useful in detecting Brachyspira species in mixed cultures including not only nonpathogenic species, such as B. innocens, but also one of the AIS pathogens. We found that MALDI-TOF MS analysis combined with the mPCR targeting tnaA and abgB was suitable for the identification of avian isolates of B. pilosicoli and B. intermedia, 2 important agents of AIS.

Occurrence of dysentery-like diarrhoea associated with Brachyspira suanatina infection on a German fattening pig farm

The anaerobic intestinal spirochaete Brachyspira (B.) suanatina was first described in 2007 but since then no further isolates have been reported from pigs. Accordingly, when the species was validly published...

Treponema pallidum Immunohistochemistry is positive in human intestinal Spirochetosis

BackgroundHuman intestinal spirochetosis (IS) has been recognized for decades, but whether it represents commensalism or a pathogenic process remains controversial. IS is diagnosed on routine stains with confirmation by silver stains but these stains are labor intensive and slow to read. We evaluated the Treponema pallidum immunostain as a diagnostic adjunct for IS.MethodsWe retrieved biopsies from 33 patients with IS for this study. Each case was tested by Warthin-Starry (WS) and T. pallidum immunohistochemistry (IHC). Species specific genotyping was performed in 3 cases.ResultsPatients with IS ranged from 22 to 82 years without gender predilection. IS involved normal (n = 15), and inflamed (n = 5) mucosa and colonic polyps (n = 13). Warthin-Starry and T. pallidum IHC were positive in all cases including both species of Brachyspira. Six (18%) symptomatic patients were treated for IS, and experienced resolution. In patients diagnosed with incidental IS on cancer screening (n = 5), follow up biopsies, without therapy, were negative for IS. T. pallidum IHC required 75 min less hands-on time than WS for performance and was faster to interpret.ConclusionsT. pallidum IHC can be used to confirm the diagnosis of IS and is easier to perform and faster to interpret than WS.

Intestinal spirochetosis: The hue is the cue

Intestinal spirochetosis: The hue is the cue

Isolation and antimicrobial susceptibility of Brachy -spira species from feces of layer chickens in Germany.

Anaerobic spirochetes of the genus Brachyspira are important pathogens causing swine dysentery (Brachyspira [B.] hyodysenteriae) and porcine intestinal spirochetosis (B. pilosicoli, PIS). In addition, avian intestinal spirochetosis (AIS) is caused by B. pilosicoli, B. intermedia and B. alvinipulli. Despite the economic impact of AIS, the disease has not received appropriate attention in Germany. This study was aimed at identifying Brachyspira spp. in Germany and determining their antimicrobial susceptibility. From 2009 to 2013, a total of 71 fecal swabs were obtained from clinically healthy layer hens from eight different commercial flocks. Brachyspira spp. culture was performed in trypticase soybean agar added with 5% sheep blood. Species determination was conducted by PCRs targeting the NADH-gen and the 16S rDNA or by nox-gene sequencing. Antimicrobial susceptibility to macrolides, lincosamides and pleuromutilins was tested by a microdilution assay. Brachyspira spp. were isolated from 40 (56.3%) swabs distributed over all eight flocks. In 26 cases, the following species were determined by PCR: B. pilosicoli (n = 16), B. intermedia (2), B. innocens (3), B. murdochii (1), mixtures of B. pilosicoli/B. intermedia (2), B. innocens/B. intermedia (1), B. innocens/B. murdochii (1). Remaining isolates were characterized by noxgene sequencing as B. "pulli" (n = 9), B. alvinipulli (3), B. intermedia (1) and as not identifiable (1). Antimicrobial susceptibility testing of 37 isolates revealed minimal inhibitory concentrations 90 (MIC90) of > 128 mg/l (tylosin), 64 mg/l (lincomycin), 8 mg/l (tiamulin) and 4 mg/l (valnemulin), respectively. Comparing to breakpoints applied to pigs, these values lie within the range of resistance. The demonstration of different Brachyspira spp., particularly B. pilosicoli, intermedia and alvinipulli in commercial layers, indicates the need of further research to assess their potential role in causing AIS in German poultry flocks. The increased antimicrobial resistance of Brachyspira spp. isolates to tylosin and pleuromutilins is likely associated with extensive use of these drugs in poultry medicine.

Immunohistochemistry application as step one for diagnosing human intestinal spirochetosis

Immunohistochemistry application as step one for diagnosing human intestinal spirochetosis

Colonic Spirochetosis: A Rare Cause of Chronic Diarrhea

Colonic spirochetosis is a condition characterized by invasion of spirochetal organisms, like brachyspira alborgi and brachyspira pilosicoli, into the colorectal epithelium. We present a case of chronic diarrhea that was eventually diagnosed as colonic spirochetosis and led to the diagnosis of HIV as well. 55 year old caucasian male with past medical history of hypertension, depression and psoriasis confined to his elbows presents to the clinic with intermittent diarrhea and associated abdominal discomfort for over one year. He has 3-4 non-bloody stools per day during an episode. He denied any fevers or weight loss. There was no significant travel history or exposure to pets or sick contacts. His family history was significant for colon cancer in his father at the age of 62. His first colonoscopy when he was 47 years old was benign. Another one from 3 years ago showed a benign distal transverse colon polyp. He has a 36 pack year smoking history but no alcohol or drug use. He is married but does not have kids. Physical exam was unremarkable. Routine stool studies including stool cultures, ova & parasites, fecal calprotectin and fecal leukocytes were all negative. CBC and CMP were unremarkable. He underwent colonoscopy which showed three colon polyps and diverticulosis of colon with possible segmental colitis. Biopsies revealed two hyperplastic polyps and one tubular adenoma. Random colon biopsy showed thickened brush border with filamentous bands. Hematoxylin-eosin staining revealed a diffuse blue fringe or “false brush border” and warthin-starry staining was used to confirm the diagnosis showing spirochetes. He was treated with flagyl for 10 days with reported improvement in diarrhea. He tested positive for HIV and was started on antiretroviral therapy. The clinical significance of colonic spirochetosis has been debated for many years in the literature. Although rare, homosexuals and HIV patients are at a higher risk of colonization and infection. Symptoms may be related to the extent of invasion beyond the epithelium and damage to the brush border. Although there is no classic endoscopic appearance, a potential association between colonic spirochetosis and hyperplastic and adenomatous polyps has been described in literature. Our case reflects the importance of considering intestinal spirochetosis as the cause of chronic diarrhea in cases with negative routine work up as well as checking their HIV status if spirochetosis is found.Figure: Random colon biopsy with H&E stain showing false brush border.Figure: Warthin Starry stain of colonic mucosa confirming spirochetes invading the epithelium.

Intestinal Spirochetosis: An Obscure Cause of Lower Gastrointestinal Bleeding

Intestinal Spirochetosis is a condition marked by anaerobic spirochetes adherence and colonization of the luminal surface of colonic epithelium with occasional penetration into the epithelium. Most cases are found incidentally on pathological evaluation of colonic biopsies taken during diagnostic or therapeutic colonoscopies. However, whether the colonization of the intestinal mucosa can be attributed to clinical symptoms is a matter of debate. Here we present a case of intermittent hematochezia due to invasion of the colonic mucosa by intestinal spirochetes. A 27 year old male with no medical history presented with four days of atypical chest pain and syncope the day prior to presentation. He also reported watery diarrhea and intermittent hematochezia for the past two weeks. A complete cardiovascular and neurologic workup was unremarkable. After a spontaneous episode of painless hematochezia he was found to have a decrease in Hgb from 14 g/dl to 10 g/dl. CRP was 6.5 and ESR was 60. All stool studies, including Clostridium difficile toxin were negative. Coagulation studies were within normal limits. Physical exam was unremarkable except for guaiac positive stool. Colonoscopy was performed, revealing mild erythematous mucosa of the terminal ileum, and a localized area of severely congested, erythematous and inflamed mucosa in the rectum. Random biopsies were taken. Intestinal spirochetes were found in biopsies of the ascending colon, transverse colon, descending colon, sigmoid colon, rectum, and cecum. Terminal ileum and rectum biopsies showed nonspecific inflammatory changes. The overwhelming spirochete invasion suggested these changes were secondary to the infectious process. Screening for all sexually transmitted diseases was negative. He was treated with metronidazole and improvement in symptoms was reported. This case demonstrates that invasive IS may develop in healthy individuals. Although many cases of asymptomatic IS have been described, cases leading to severe gastrointestinal symptoms are rare. No current methods exist to prove a direct relationship between histologic findings of IS and active disease thus leaving IS as the diagnosis of exclusion. Diagnosis requires random colonic biopsies followed by direct visualization via histologic staining, and may be confirmed by fluorescence in situ hybridization. Treatment of IS is controversial and ultimately should be dictated by the presence of symptoms, after all other etiologies have been ruled out.Figure: Erythematous Colonic Mucosa.Figure: False Brush Border Intestinal Colonization of Spirochetes along the colonic epithelium.

Acute Intestinal Spirochetosis Presenting as an IBD Mimicker

25 year old male with a PMhx significant for polysubstance abuse including cocaine and crystal meth presented to the ED with a 1 month history of intermittent hematochezia with associated loose stools and lower abdominal pain.He took high dose NSAIDs for pain with mild relief. ROS was positive for subjective fevers, night sweats, and chills for the preceding 4 days. He used intra-rectal cocaine and crystal meth injection with a needleless syringe. He reported 5 male sexual partners over the preceding 6 months with occasional condom use.Family history was negative for gastrointestinal illness. Physical exam was normal. Labs were significant for Hgb of 11.4 and mild leukocytosis of 12.3. CMP was normal.Stool samples for leukocytes, ova and parasites, cultures and Clostridium difficile toxin tested negative.CT abdomen exhibited marked rectal thickening with perirectal induration and numerous mildly enlarged, reactive perirectal lymph nodes.The primary diagnosis was inflammatory bowel disease. Colonoscopy revealed a continuous area of ulcerated mucosa in the rectum. Biopsies throughout the entire colon were taken. The cecal, ascending, and transverse colon biopsies demonstrated surface collocytes showing a characteristic basophilic fuzzy coating characteristic of intestinal spirochetosis.The immunohistochemical stain of rectal biopsies was also positive for spirochetes. However, these biopsies did not show overt evidence of intestinal spirochetosis and were strongly suspicious for syphilis.A diagnosis of colonic spirochaetosis was made. Further laboratory investigations included a negative HIV test and fluorescent treponemal antibody absorption (FTA-ABS). Patient was treated with Doxycycline for 4 weeks to cover syphilis. He was also started on a10-day course of metronidazole to treat the intestinal spirochetosis.We present an unusual case of a patient with features of both rectal syphilis and intestinal spirochetosis; Two separate conditions requiring different treatment.The purpose of this report is to raise awareness that intestinal spirochaetosis is a possible but rare cause of bloody diarrhea and presents as an IBD mimicker.Intra-rectal cocaine and methamphetamine are risk factors and these patients should be screened with RPR while awaiting pathology results regardless of their immune system status.History taking, physical exam, endoscopic findings and pathological review are essential in obtaining the accurate diagnosis, and furthermore treatment options.Figure: Colonoscopy with a continuous area of nonbleeding ulcerated mucosa with stigmata of recent bleeding in the rectum.Figure: Silver stained slide from the transverse colon showing intestinal spirochetosis.Figure: H&E stained slide from the rectum showing chronic inflammation, there is some distortion of the normal colonic architecture and increased mixed inflammatory cells in the lamina propria.

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.

An Uncommon Cause of Diarrhoea and the Importance of an Internist Approach.

BackgroundHuman intestinal spirochetosis is a condition defined by the presence of spirochetes attached to the colonic epithelium. Brachyspira aalborgi and Brachyspira pilosicoli may cause the disease in humans.Case reportWe describe the case of a 58-year-old patient who presented with epigastric abdominal pain and diarrhoea. He was thought to be having a myocardial infarction and underwent an angiogram with subsequent stenting of the circumflex coronary artery. However, the pain and diarrhoea were still present after the procedure and the patient now had sepsis. An exploratory laparotomy was inconclusive. The patient improved on intravenous antibiotics and was discharged, but returned to the emergency department 2 days later with the same complaints. He was then admitted to an internal medicine ward where the diagnosis of intestinal spirochetosis was made. The patient was started on metronidazol and completed a 10-day antibiotic course with full recovery of his symptoms.ConclusionThis case highlights the importance of an internist-based approach that could have prevented two invasive procedures and the accompanying risks.LEARNING POINTSUncommon causes of diarrhoea are a diagnostic challenge.Errors of clinical judgement can lead to invasive and potentially harmful procedures.An internist-based approach can prevent diagnostic mistakes and be in the patient’s best interests.

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.

Clinical significance of human intestinal spirochetosis: a retrospective study.

The clinical and pathological features of human intestinal spirochetosis (HIS) are not well known. Here we report 55 patients with HIS who were diagnosed at our institution during the past 5 years. Seven patients presented with symptoms such as abdominal pain or diarrhea, while the others were incidentally diagnosed during screening colonoscopy. Most patients had non-specific endoscopic findings, including intestinal edema or erosion. The diagnosis of HIS was histologically confirmed via hematoxylin and eosin staining, periodic acid-Schiff staining, and/or immunohistochemistry using anti-Treponema pallidum antibody. Among the 55 patients, five were diagnosed with diseases other than HIS (amoebic colitis, three;ulcerative colitis, one). Sixteen patients were treated with either amoxicillin or metronidazole;only metronidazole proved to be effective. The clinical significance of asymptomatic HIS remains unknown. Some case reports suggest a risk for increased severity in patients with immunodeficiency and/or sexually transmitted diseases. Therefore, aggressive treatment for HIS should be considered, particularly in high-risk patients.

An Investigation into the Etiological Agents of Swine Dysentery in Australian Pig Herds.

Swine dysentery (SD) is a mucohemorrhagic colitis, classically seen in grower/finisher pigs and caused by infection with the anaerobic intestinal spirochete Brachyspira hyodysenteriae. More recently, however, the newly described species Brachyspira hampsonii and Brachyspira suanatina have been identified as causing SD in North America and/or Europe. Furthermore, there have been occasions where strains of B. hyodysenteriae have been recovered from healthy pigs, including in multiplier herds with high health status. This study investigated whether cases of SD in Australia may be caused by the newly described species; how isolates of B. hyodysenteriae recovered from healthy herds compared to isolates from herds with disease; and how contemporary isolates compare to those recovered in previous decades, including in their plasmid gene content and antimicrobial resistance profiles. In total 1103 fecal and colon samples from pigs in 97 Australian herds were collected and tested. Of the agents of SD only B. hyodysenteriae was found, being present in 34 (35.1%) of the herds, including in 14 of 24 (58%) herds that had been considered to be free of SD. Multilocus sequence typing applied to 96 isolates from 30 herds and to 53 Australian isolates dating from the 1980s through the early 2000s showed that they were diverse, distinct from those reported in other countries, and that the 2014/16 isolates generally were different from those from earlier decades. These findings provided evidence for ongoing evolution of B. hyodysenteriae strains in Australia. In seven of the 20 herds where multiple isolates were available, two to four different sequence types (STs) were identified. Isolates with the same STs also were found in some herds with epidemiological links. Analysis of a block of six plasmid virulence-associated genes showed a lack of consistency between their presence or absence and their origin from herds currently with or without disease; however, significantly fewer isolates from the 2000s and from 2014/16 had this block of genes compared to isolates from the 1980s and 1990s. It is speculated that loss of these genes may have been responsible for the occurrence of milder disease occurring in recent years. In addition, fewer isolates from 2014/16 were susceptible to the antimicrobials lincomycin, and to a lesser extent tiamulin, than those from earlier Australian studies. Four distinct multi-drug resistant strains were identified in five herds, posing a threat to disease control.

Intestinal Spirochetosis in a Patient with a History of Prostate Cancer

Intestinal spirochetes were first described by father of microbiology, van Leeuvenhoek in his own stool. Here we present a case of a male with a history of prostate cancer with a diagnosis of intestinal Spirochetosis. A 77-year-old man presented to the clinic with a 1 week history of non bloody diarrhea. Patient initially attributed the diarrhea to taking folic acid, flax seed oil and prunes. The diarrhea had stopped after patient stopped these medications. Last colonoscopy was done a several years ago with benign polyps. Patient had a prostatectomy in 2009. The patient denied abdominal pain, nausea or vomiting. Patient was in a heterosexual relationship no recent new partners. Examination showed a well- nourished man with no remarkable findings on physical examination. Colonoscopy was performed that showed normal-appearing mucosa. Random biopsy specimens were obtained from the colon. Histological examination was significant for Spirochetosis with no increased intraepithelial lymphocytosis or thickened collagen layers. The diarrhea had resolved at the time of the colonoscopy and patient was not treated further for the Spirochetosis. Patient was to advised to repeat colonoscopy in 5 years. There is some discussion on whether Spirochetosis can be considered a true gastrointestinal pathogen as there can be the presence of the parasite without any inflammation or gastrointestinal symptoms. Food and water hygiene, immunocompromised status, sexual practice all contribute to the prevalence of the disease. Patients can present with variety of symptoms including hematochezia watery diarrhea, abdominal pain or can be found incidentally on colonoscopy in asymptomatic patients. Gram- negative bacteria Brachyspira aalborgi and Brachyspira pilosicoli appears to be the most common pathogen associated with the disease however these are not well defined. Further speciation was not done on the cultures in our case. For diagnosis spirochetes are seen adhering to the colorectal epithelium on histological exploration. Basophilic organisms are seen on luminal surface of colonic epithelia. Metronidazole or clarithromycin has been used in many cases as treatment with success. Observation without treatment has also been used in patients with mild disease. In our patient given that his diarrhea was resolved by the time of the biopsy, observation without treatment was utilized. Patient's diarrhea resolved and continues to remain symptom free.

Inflammation, Genetics, Dysbiosis, and the Environment

Chronic and complex gut syndromes are complex to diagnose and manage, but good clinicopathologic correlation, recognition of new entities, understanding (and understanding the limits) of genetic susceptibility and the importance of the microbiome, dysbiosis and influence of the environmental allows development of new models for diagnosis. An awareness of overlap in chronic gut syndromes has been clarified by the realization that inflammatory pathways involved in chronic gut disease can arise through variable gene expression that is influenced by the environment in susceptible individuals. Recent advances in diagnosis of inflammatory bowel disease and diverticular disease may be aided by genetic tests but at present, pathology and some simple biomarkers such as C-reactive protein and fecal calprotectin are still mainstream investigative measures. When made aware of the importance of these recent developments in chronic gut disease, histopathologists can easily recognize colonic spirochetosis and microscopic colitis. The role of the microbiome alongside interaction with the environment, are now recognized as key players in complex diseases. Integration of appropriate and cost-effective tests into new paradigms will surely advance patients' well-being and allow development of curative-targeted therapies rather than current treatments which, in many cases, merely alleviate symptoms.