Post-infectious IBS, tropical sprue and small intestinal bacterial overgrowth: the missing link.

Evidence is emerging that IBS, a hitherto enigmatic disorder thought to be predominantly related to psychological factors, has a microorganic basis in a subset of patients with the disease. Post-infectious IBS (PI-IBS), commonly of the diarrhoea-predominant subtype (defined as new development of IBS following acute infectious diarrhoea), is one such condition known to occur in up to 10-30% individuals after acute gastroenteritis. However, following acute infectious gastroenteritis, patients can also develop post-infectious malabsorption syndrome (PI-MAS), popularly known as tropical sprue. As no study on PI-IBS has rigorously excluded tropical sprue by appropriate investigations, including small intestinal biopsy, the frequency of tropical sprue among patients with PI-IBS is not known. Small intestinal bacterial overgrowth (SIBO) has been suggested to be associated with IBS in general, and in particular diarrhoea-predominant IBS, including PI-IBS. SIBO is also known to be associated with tropical sprue. As both IBS, particularly the subset probably associated with SIBO, and tropical sprue improve with antibiotic treatment, we provide evidence and an explanatory model to support a link among these disorders.

Pathogenesis of tropical sprue: a pilot study of antroduodenal manometry, duodenocaecal transit time & fat-induced ileal brake.

BACKGROUND & OBJECTIVES: Small intestinal bacterial overgrowth (SIBO) due to ileal brake-induced hypomotility may cause tropical sprue (TS). We evaluated effect of infusion of fat or placebo in duodenum randomly in patients with TS and healthy controls on antroduodenal manometry (ADM) and mediators of ileal brake, and duodenocaecal transit time (DCTT). METHODS: ADM and DCTT (lactulose hydrogen breath test, HBT) were evaluated with placebo and fat in eight controls and 13 patients with TS (diagnostic criteria: tests showing malabsorption of two unrelated substances, abnormal duodenal histology, absence of other causes, response to antibiotics and folate). RESULTS: Patients with TS (6 had SIBO by glucose HBT) were similar in age and gender with controls. After fat infusion, proximal gut motility index (MI) was reduced compared to fasting state in TS, and DCTT was longer in TS than controls (200 min, 120-380 vs. 130, 70-160, P=0.001), though comparable after placebo (70 min, 30-140 vs. 60, 40-90). TS patients had higher PYY and neurotensin than controls after fat infusion. DCTT after fat infusion correlated with plasma level of PYY in TS but not in controls. Post-fat PYY and neurotensin levels were higher in TS with lower BMI (<16 kg/m [2] ) than those with higher BMI. Parameters of ileal brake (post-fat DCTT, PYY and neurotensin) were higher in patients with than without SIBO. INTERPRETATION & CONCLUSIONS: Fat infusion reduced proximal gut MI, increased DCTT, PYY, and neurotensin among patients with TS. Malabsorbed fat might cause exaggerated ileal brake reducing gut motility, promoting SIBO and bacterial colonization and malabsorption in TS.

Tropical malabsorption.

Malabsorption is an important clinical problem both in visitors to the tropics and in native residents of tropical countries. Infections of the small intestine are the most important cause of tropical malabsorption. Protozoal infections cause malabsorption in immunocompetent hosts, but do so more commonly in the setting of immune deficiency. Helminth infections occasionally cause malabsorption or protein-losing enteropathy. Intestinal tuberculosis, chronic pancreatitis and small-bowel bacterial overgrowth are important causes of tropical malabsorption. In recent years, inflammatory bowel disease and coeliac disease have become major causes of malabsorption in the tropics. Sporadic tropical sprue is still an important cause of malabsorption in adults and in children in South Asia. Investigations to exclude specific infective, immunological or inflammatory causes are important before considering tropical sprue as a diagnosis. This article briefly reviews the management of tropical sprue and presents an algorithm for its investigation and management.

Tropical sprue in two foreign residents, with evidence of Tropheryma whippelii in one case.

Tropical sprue is a rare disease in travelers. Its etiology remains unclear. We report two cases of tropical sprue occurring in long-term residents in Nepal and Cameroon. In one case, Tropheryma whippelii, the agent of Whipple's disease, was identified. Many infectious agents have been suggested to be the etiological agent of tropical sprue, but no association with Whipple's disease has yet been reported.

Tropical sprue is associated with contamination of small bowel with aerobic bacteria and reversible prolongation of orocecal transit time.

BACKGROUND: In tropical sprue (TS), response to antibiotics may suggest a role for bacterial contamination of the small bowel, which is known in diseases with prolonged orocecal transit time (OCTT). METHODS: We studied 13 patients with TS (diagnosed by standard criteria) for frequency, nature and degree of bacterial contamination of the small bowel by quantitative culture of jejunal aspirate, glucose hydrogen breath test (GHBT), and OCTT by lactulose hydrogen breath test before and after treatment. Twelve patients with constipation-predominant irritable bowel syndrome (IBS) and 12 healthy subjects served as controls. RESULTS: Ten of 13 patients with TS had bacterial contamination compared with 3/12 with IBS (all aerobic, P < 0.05). Median colony count in TS (36 000 CFU/mL, 400 to > 100 000) was higher than IBS (700 CFU/mL, 100-1000, P < 0.05). Gram-negative aerobic bacilli were commonly isolated in TS but not in IBS. Median OCTT was longer in TS (180 m, 40 - 240) than IBS (110 m, 70 - 150, P = 0.008) and healthy subjects (65 m, 40 - 110, P = 0.0007, Wilcoxon rank sum test). Orocecal transit time in TS correlated with fecal fat (Spearman's rank correlation coefficient 0.69, P < 0.05). Orocecal transit time and fecal fat, repeated in 8/13 patients, decreased with treatment for TS (195 m, 130-240 vs 125 m, 90-200, P = 0.02; 8 g/24 h, 6.8-19.6 vs 7 g/24 h, 4.2-9, P = 0.04, respectively). CONCLUSION: Aerobic bacterial contamination of the small bowel is common in patients with TS. Prolonged OCTT in TS correlated with fecal fat and normalized in a subset of patients after treatment.

Infectious agents and the etiology of chronic idiopathic diseases.

At the end of the nineteenth century, the field of microbiology was born, and the infectious nature of many previously unexplained diseases was illuminated as powerful new technology was applied. At the end of the twentieth century, the etiology of myriad chronic diseases remains unexplained. We have argued that many of these diseases have clinical, epidemiological, and pathological features that suggest a role for microbes in their pathogenesis. Although definitive evidence of microbial disease causation is lacking, we believe that new technologies, such as sequence-based microbial identification, will successfully be applied to many of these chronic idiopathic diseases in the near future. As novel pathogens and previously described pathogens are revealed as the causative agents for some of these conditions, new diagnostic, preventive, and therapeutic modalities may emerge, transforming some diseases from idiopathic and chronic, to infectious and curable.

Prevalence of neutralising antibodies to Berne virus in animals and humans in Vellore, South India. Brief report.

In Southern India the prevalence of neutralising antibody to Berne virus was high in sera obtained from cattle (49%), horses (38%), and sheep (36%). Neutralising antibody was not detected in sera from humans and monkeys.

The human intestinal microflora.

The major host defense mechanisms against bacterial overgrowth in the small bowel are the normal propulsive activity of the bowel itself and gastric acid secretion. Microbial interactions are a major factor in regulating the indigenous bacterial flora. Studies of the bacterial enzymes of the gut suggest that changes in diet may lead to marked changes in the colonic flora. Antibiotics affect the composition of the colonic microflora. The microflora also influence the degradation of mucin, the conversion of urobilin to urobilinogen, of cholesterol to coprostanol, and the production of short chain fatty acids. Current interests are focused on the bacterial flora of tropical sprue, the role of bacteria in colorectal cancer, and the involvement of intestinal microflora in the enterohepatic circulation of sex steroid hormones.

Chronic enterocyte infection with coronavirus. One possible cause of the syndrome of tropical sprue?

A man with a gastrojejunostomy and intestinal malabsorption was found to be excreting large numbers of coronavirus-like particles in his stools over a period of at least eight months. Coronavirus-like particles were found in vesicles in degenerating jejunal enterocytes in all of five jejunal biopsies. In a review of electron micrographs, similar structures were found in biopsies from three of 12 patients with classical chronic tropical sprue and in one patient with a sprue-like syndrome associated with agammaglobulinaemia. The hypothesis is advanced that infection with this virus may produce enterocyte damage and may be one cause of the syndrome of tropical sprue.

Intestinal bacteria in patients with tropical sprue.

Ten samples of jejunal fluid from patients with tropical sprue and 11 from controls without this disease were examined bacteriologically, using techniques designed to obtain the optimal yield of aerobic and anaerobic bacteria. Total colony counts did not differ significantly in the two groups studied. The organisms isolated comprised a wide range of aerobic and anaerobic bacteria. With the exception of Haemophilus species, no bacterial group was isolated in significantly greater numbers in sprue patients than in controls. The pathogenesis of tropical sprue in Natal is discussed in the light of these findings.

Bacterial colonization of the upper intestine in mild tropical malabsorption.

The bacterial flora of the upper intestine has been examined in symptomatic expatriate adults with mild tropical malabsorption, without steatorrhoea, persisting for many months after return to a western environment. Seven of the 11 patients had enterobacteria in luminal fluid or mucosal samples in numbers ranging from 10(3) to 10(8) per ml or per g. The most common isolate was Klebsiella pneumoniae (in four cases); Citrobacter freundii, Serratia marcescens and Pseudomonas spp. were also detected. The signficance of bacterial colonization in the pathogenesis of mild tropical malabsorption is discussed.

[II. Etiological classification of the small bowel diseases (author's transl)]. / II. Classification étiologiques des maladies de l'intestin grêle.

A new classification of the small bowel diseases is proposed according to - the physiopathology; - the anatomo-pathology; - the etiology. In this second part, the ethiological classification is developed. One may distinguish the post-surgical lesions, congenital defects, the side-effects of drugs and the vascular lesions. Allergy and infection are especially studied. The main problems which may be solved in a next future are: the mechanism of chronic infections, the biochemical pathology and especially the normal and pathological immunology.