The gastrointestinal infection - psychiatric connection ...
Spirochetes in the intestine
Note see also this file: Transmission-Bb-contact.htm
Bb-antigen has been demonstrated by PCR in colostrum from cows, splenectomized mice and 2 women.
Transmission to offspring has been demonstrated in cows and mice.
Relief of psychiatric symptoms in a patient with Crohn's disease after metronidazole
Sandler RH, Bolte ER, Chez MG, Schrift MJ. Clin Infect Dis 2000 Jan;30(1):213-4 PMID: 10619762 PDF (page 213)
The scant reports of an increased prevalence of gastrointestinal (GI) disease in psychiatric patients  may not adequately reflect the extent of this association, since these patients may not complain of GI symptoms until specifically questioned .
Although there are scattered reports of a possible association between Crohn’s disease and psychiatric illness , to our knowledge, we report the first case of a patient with Crohn’s disease whose psychiatric symptoms abated following antimicrobial treatment.
A 14-year-old boy developed insomnia, irritability, severe impulsivity, aggressive behavior, and thought disorder consistent with atypical psychosis. Routine physical evaluation noted anemia but was otherwise unremarkable (the erythrocyte sed-imentation rate [ESR] was not determined). A series of anti-psychotic medications, including nortriptyline, fluoxetine, risperidone, haloperidol, perphenazine, amantadine, and olan-zapine, were then administered unsuccessfully.
At 15.7 years of age, he had nausea, vomiting, fever, and blood per the rectum and presented to an outlying institution.
Subsequent colonoscopy with biopsies showed focal severe colitis on the right side consistent with Crohn’s disease. Treatment with metronidazole (250 mg t.i.d.), prednisone (40 mg/d), and mesalamine (80 mg t.i.d.) was initiated, and within 2 weeks, both his GI and psychiatric symptoms dramatically abated.
Although the mesalamine dosage was continued without change, metronidazole treatment was discontinued at 4 weeks, and the prednisone dosage was tapered to a maintenance dosage of 15 mg every other day over 3 months.
Subsequent deterioration in behavior was first noted 2 months after metronidazole treatment was discontinued (while he was still receiving mesalamine treatment and the maintenance dosage of prednisone). At admission to Rush Children’s Hospital (
Colonoscopy confirmed active lesions in the right colon consistent with Crohn’s disease. There was no evidence of luminal stricture or narrowing related to Crohn’s disease. Electroencephalograms obtained throughout a 24-h period were normal. Treatment with prednisone (60 mg/d) and mesalamine (800 mg t.i.d.) was initiated for his Crohn’s disease, with the prednisone dosage tapered to 20 mg/d after several months. Although his subtle GI symptoms resolved, his psychotic condition failed to im-prove, despite further treatment with antipsychotic agents, in-cluding lithium, pimozide, valproic acid, fluphenazine, and clozapine.
Finally, 3 months after the psychiatric relapse, a second 1-month course of metronidazole (500 mg t.i.d. orally for 30 days) was initiated. Within 3 weeks, a dramatic improvement in his psychiatric condition was again noted, and by 5 weeks, he was essentially normal and not receiving any antipsychotic medication.
Five months later, he remained free of psychiatric and GI symptoms, although repeated colonoscopy confirmed that his Crohn’s disease was quiescent.
The cause of the observed improvement in this patient’s psychiatric condition is unknown. Treatment with prednisone and mesalamine was continued throughout his course, and although these agents may have contributed to improvement in his condition, the behavioral changes were not noted on either occasion until the addition of metronidazole therapy. This finding suggests that improvement may have been due, at least in part, to this latter agent.
If this fact is true, the mechanism of action is not known. It is intriguing to speculate that benefit may have been secondary to an antimicrobial action of metronidazole. For example, it is at least conceivable that an opportunistic neurotoxin-producing organism may have colonized the GI tract. Both Crohn’s disease  and broad-spectrum antimicrobials are known to alter the GI flora, which might have allowed such colonization. This patient had both risk factors, the latter including frequent exposure to broad-spectrum antibiotics for several years prior to the onset of his psychiatric symptoms.
Psychiatric symptoms have previously been associated with altered intestinal flora. For example, patients with D-lactic acidosis (a condition caused by bacterial overgrowth in the small intestine) may present with a range of behavioral changes (e.g., hostility, slurred speech, stupor, deranged mental status, dizziness, and ataxia), and treatment with oral antibiotics usually results in rapid improvement . Whatever the mechanism, further research into a possible gut microbe-brain connection may be helpful.
Richard H. Sandler, 1 Ellen R. Bolte, 1
Michael G. Chez, 2 and Michael J. Schrift 3
1 Pediatric Gastroenterology and Nutrition,
2 Pediatric Neurology, and
3 Pediatric Psychiatry, Rush Children’s Hospital,
1. Mäkikyrö T, Karvonen JT, Hakko H, et al. Comorbidity of hospital-treated psychiatric and physical disorders with special reference to schizophrenia: a 28 year follow-up of the 1966
2. Gupta S, Masand PS, Kaplan D, Bhandary A, Hendricks S. The relationship between schizophrenia and irritable bowel syndrome (IBS). Schizophr Res 1997; 23:265-8.
3. Holroyd S, DePaulo JR Jr. Bipolar disorder and Crohn’s disease. J Clin Psychiatry 1990; 51:407-9.
4. Van de Merwe JP, Schroder AM, Wensinck F, Hazenberg MP. The obligate anaerobic faecal flora of patients with Crohn’s disease and their first-degree relatives. Scand J Gastroenterol 1988; 23:1125-31.
5. Traube M, Bock J, Boyer J. D-lactic acidosis after jejunoileal bypass: identification of organic anions by nuclear magnetic resonance spectroscopy. Ann Intern Med 1983; 98:171-3.
These authors didn't consider a spirochetal
but here are a few other references on gastrointestinal spirochetosis
- if you're aware of more references on this issue, please add them and return the message to me at:
kroun (at) ulmar.dk
a case report and review of literature.
Singh S, Rattan A, Samantaray JC. Trop Gastroenterol 1990 Jul-Sep; 11(3): 152-7 PMID: 2267674
Spiral shaped bacteria have frequently been demonstrated from human faeces. Their role in causation of disease is, however, controversial; as they have been found to colonise the lower gastrointestinal tracts of both symptomatic and asymptomatic individuals. Here we report a case in which spiral shaped motile, gram negative and nonflagellated bacteria, probably belonging to the genus Borrelia, were demonstrated and associated with acute bloody diarrhea in a cardiac patient. The condition could successfully be treated with short course of Metronidazole. The relevant and up to date literature on this problem is also reviewed.
Invasive intestinal spirochetosis: a report of
Padmanabhan V, Dahlstrom J, Maxwell L, Kaye G, Clarke A, Barratt PJ. Pathology 1996 Aug;28(3):283-6 PMID: 8912364
We here report on three patients with gastrointestinal symptoms in whom spirochetes were found in colonic biopsies. The patients, heterosexual adults, were not immunocompromised. Electron microscopy was performed on colonic biopsies from each of the three patients. Apart from the basophilic band consisting of spirochetes, the mucosa was normal in two patients on light microscopy and showed mild inflammation in the other one. However on electron microscopy there was invasion of the colonic epithelial cells, macrophages, goblet cells and Schwann cells by spirochetes, and stunting of the microvilli. The spirochetes conformed to the morphology of Brachyspira aalborgi, and no other infective etiology or pathology could be identified in these patients to account for their symptoms. Since the clinical significance of intestinal spirochetosis is uncertain, antibiotics were not administered to any of the three patients and all three improved symptomatically with non-specific treatment.!
Intestinal spirochetosis, previously thought to be non-invasive and non-pathogenic in humans, may be invasive and may be the cause of gastrointestinal symptoms in some patients.
Gastrointestinal pathology in children with Lyme disease
J Spiro Tick Diseases 1996; 3:101-104
Fried MD, Duray PH, Pietrucha D
Ten children between the ages of 8 and 19 with Lyme disease presented with chronic gastrointestinal symptoms. Biopsy evidence of inflammation was found in the stomach, duodenum, and colon. Pathologies included gastritis, duodenitis, gastric ulcer, colitis, and a histopathology resembling Crohn's disease. Spirochetes with the microscopic appearance of Borrelia were found in five patients with chronic inflammatory conditions of the gastrointestinal tract. The inflammation may have been due to the spirochete itself, a reactive product related to their presence in the gastrointestinal tract, or a consequence of medications used to treat Lyme disease.
The Spectrum of Gastrointestinal Manifestations in Children and
Adolescents with Lyme Disease
J Spiro Tick Diseases 1999; 6(4):89-93
Fried MD, Abel M, Pietrucha D, Kuo Y, Bal A
A clinical diagnosis of Lyme disease was made in 15 consecutive patients between the ages of 8 and 20 years who presented with a history of an erythema migrans rash followed by chronic gastrointestinal symptoms and multiple organ system complaints. Endoscopic evaluation was performed to assess the gastrointestinal mucosa and to obtain biopsies for polymerase chain reaction (PCR) to the outer surface protein A (Osp A) of Borrelia burgdorferi. As age matched controls, 10 patients with biopsy-proven Crohn's disease were also tested by PCR. The laboratories assessing the histopathology and performing the PCR were blinded to the diagnosis of all specimens.
The presence of B burgdorferi DNA in the gastrointestinal tract was confirmed by PCR in all of the patients with the clinical diagnosis of Lyme disease who had chronic gastrointestinal symptoms and in two control subjects with Crohn's disease. Biopsy evidence of chronic gastritis, chronic duodenitis, and chronic colitis was found in patients with Lyme disease who had chronic gastrointestinal symptoms and was associated with the presence of B burgdorferi.
The chronic gastrointestinal symptoms that occurred within 6 months of an erythema migrans rash and Lyme disease may be attributed to a direct effect or immune mediated response to B burgdorferi.
BC, personal message dated 23-05-99:
After a 5 year long history of Lyme disease including documented EM, cardiac symptoms, neurologic symptoms, numerous positive Lyme disease serologies (ELISA, IFA, Western blot), and despite multiple long-term courses of antibiotics, IV as well as oral, gastrointestinal symptoms developed. A colon biopsy was PCR positive for the OSP A gene indicating the presence of B. burgdorferi and electron microscopy studies performed at an independent laboratory (NIH) revealed rare structures that are noted as suspicious for B. burgdorferi in the tissue with chronic inflammation.
As a last statement BC writes: "In anticipation of any possible sentiment that my case demonstrates the ineffectiveness of long term antibiotics, I say au contraire mon frere - at least I can function while under their influence."