The presence of intestinal spirochetes in human faeces has been recognized in the late 1800’s [2]. The term intestinal spirochetosis was coined in 1967 by Harland and Lee who recognized spirochetes adherent to the cellular membrane of apical cells in the colonic epithelium [3]. This histological appearance is considered to be the hallmark of this infection.

His past medical history revealed a recurrent aphthous stomatitis, and his family history was positive for celiac disease (one maternal cousin), irritable bowel syndrome (one paternal uncle) and bowel cancer (paternal grandfather). His growth parameters were normal and the physical examination revealed palpable stool masses in the left lower abdomen. Based on the clinical presentation, the differential diagnosis included inflammatory bowel disease, celiac disease, infectious colitis and intestinal polyp. Laboratory investigations showed no biological markers for inflammation (normal full blood count, ESR: 5mm/h and CRP: 0.28mg/l) or celiac disease. Fecal calprotectin was not measured. Stool cultures for conventional enteric pathogens (Salmonella, Shigella Campylobacter) were negative. Upper and lower endoscopy revealed mucosal oedema in the sigmoid and rectum, which was probably due to the required bowel preparation for colonoscopy. Histological examination on conventional hematoxylin and eosin stain of the colonic biopsy specimens revealed a fuzzy band on the surface of the enterocytes. This finding was highly suggestive of intestinal spirochetosis (Figure ​(Figure1).1). Interestingly, no specific inflammatory reaction or lesions were observed. The diagnosis of intestinal spirochetosis was confirmed by Fluorescence in situ hybridization (FISH), confirming the presence of Brachyspira aalborgi (Figure ​(Figure22).

Spirochetes are currently divided into three phylogenetic groups: Spirochaetaceae including Borrelia, Spirochaeta, Spironema and Treponema; Leptospiraceae including Leptonema and Leptospira; and finally Brachyspiraceae containing the intestinal spirochetes of Brachyspira (Serpulina)[1]. Brachyspira aalborgi (B. aalborgi) and Brachyspira pilosicoli (B. pilosicoli), the two members of Brachyspiraceae family, are both described in humans and are considered as cause of human intestinal spirochetosis [13]. The anaerobic weakly β-haemolytic intestinal spirochete B. aalborgi, was first isolated in 1982 in the stool of a patient from Denmark [14], whereas B. pilosicoli is responsible for colitis and typhlytis in pigs, poultry and other species, acting more as zoonotic agent [15]. Since 1997, Brachyspira spp. have been included in the list of human enteropathogenic bacteria [16]. These two spirochetes are slow growing fastidious anaerobes and require specific media, with estimated growth times of 6 days for B. pilosicoli and up to 2 weeks for B.aalborgi[17]. Morphologically, they are coiled Gram-negative bacilli and are mobile in liquid environment due to the presence of flagella. Generally they are considered non invasive microorganisms but systemic spread of B.pilosicoli has been documented by culture of blood specimens obtained from critically ill patients [18]. Concomitant infection by B.aalborgi and B.pilosicoli is described but rare [19]. These spirochetes are susceptible to different antibiotics, such as metronidazole, meropenem, chloramphenicol, ceftriaxone and tetracycline, whereas a 60% resistance rate to ciprofloxacine has been observed [20]. Little is known about the way of transmission, but it seems likely to occur by faecal-oral route (contaminated water, colonized/infected faeces) [19]. Due to the higher prevalence in homosexual men, sexual transmission has been suggested as well [21]. Possible co-infection with others microorganisms like Helicobacter pylori, Enterobius vermicularis, Shigella flexneri, Neisseria gonorrhoeae, Entamoeba histolytica, Blastocystis hominis, and Ascaris is possible, rendering clinical significance difficult [2].

The prevalence varies considerably in geography and immune condition. In developed countries for example ranges between 1.1-5% can be observed, with an increase in homosexual men and HIV positive patients [1]. In a recent study from Japan the incidence of human intestinal spirochetosis in patients aged from 35 to 75 years was 0.4% and therefore lower than in Western countries [22]. The paucity of epidemiologic data is probably due to several reasons: firstly: the endoscopist not always takes routine multiple biopsies in healthy looking mucosa; secondly: the pathologist actively has to look for spirochetes and can easily miss them if not familiar with its appearance and thirdly: it is not a routine diagnosis by microbiologist either [11].

In most cases, intestinal spirochetosis is asymptomatic and presents as accidental findings during a screening colonoscopy for other reasons [23]. However, infected children usually complain of persistent diarrhoea, rectal bleeding, constipation, abdominal pain, weight loss, failure to thrive, nausea and lack of appetite [24]. The severity of disease can vary from asymptomatic colonisation to invasive and rapidly fatal progression [25], but there appears to be no correlation with degree of immunodeficiency in HIV positive patient and the extent of disease [1]. Due to this unspecific presentation, differential diagnosis should include inflammatory bowel disease, infectious, ischemic or pseudomembranous colitis and rectocolic carcinoma [24]. Colonic involvement is documented from distal to proximal, including rectum and appendix [26]. Mucosal appearance on endoscopy is not helpful in making the diagnosis, as it can be normal, polypoid, and erythematous, or just show unspecific lesions [27]. In a large Australian case series of 113 adult patients presenting with intestinal spirochetosis, 90 percent of colorectal specimens showed no morphological alterations, whereas the remaining cases had other possible causes for inflammation [23]. Histological appearance of a diffuse blue-fringe (better seen in hematoxylin-eosin or a silver stain), 3-6μm thick, along the border of intestinal epithelial layer, referred to as the « false brush border » is highly suggestive [1]. The surrounding cytostructure may show inflammation with slight oedema, infiltrate of monocytes, lymphocytes, plasma cells and neutrophils in the lamina propria, as well as elongated and hyperplastic crypts [28]. On electron microscopy, spirochetes are attached perpendicularly to the epithelial membrane of the enterocytes and the microvilli appear shortened or depleted [3]. Analysis of specimens from infected individuals even though rare has shown spirochetal invasion of colonic epithelial cells, macrophages, goblet cells and Schwann cells [29]. Histologically it is not possible to distinguish B.pilosicoli from B.aalborgi, therefore genetic methods have been developed in order to identify Brachyspira species from stool or tissue samples. Fluorescent in situ hybridization using oligonucleotide probes targeting 16S or 23S rRNA of B. aalborgi and B. pilosicoli allow visualisation and identification of this microorganism [28].