Bacterial Overgrowth and Dysbiosis: Role in Systemic Diseases

Leonard Weinstock, MD, Washington University School of Medicine

Bacterial Overgrowth – General references

Arranz E, O’Mahony S, Barton JR, et al. Immunosenescence and mucosal immunity: Significant effects of old age on secretory IgA concentrations and intraepithelial lymphocyte counts. Gut 1992;33:882-6.

Agrawal S, Misra R, Aggarwal A. Anemia in rheumatoid arthritis: high prevalence of iron-deficiency anemia in Indian patients. Rheumatol Int 2006;26:1091-5.

Attar A, Flourie B, Rambaud JC, et al. Antibiotic efficacy in small intestinal bacterial overgrowth-related chronic diarrhea: A crossover, randomized trail. Gastroenterology 1999;117:794-7.

Bardhan FK, Gyr K, Begliner C, et al. Diagnosis of bacterial overgrowth after culturing proximal small bowel aspirate attained during routine upper gastrointestinal endoscopy. Scand J Gastroenterol 1992;27:253-6.

Beer RJ. The relationship between Trichuris trichiura (Linnaeus 1758) of man and Trichuris suis (Schrank 1788) of the pig. Res Vet Sci 1976;20:47.

Best WR, Becktel JM, Singleton JW, Kern, Jr F. Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. Gastroenterology 1976;70:439.

Biadoo L, Kundu R, Berenbaum PL, et al. Rifaximin is an effective treatment for small bowel bacterial overgrowth. Gastroenterology 2005; DDW Abstract.

Browning GG, Buchan KA, Mackay C. The effect of vagotomy and drainage on the small bowel flora. Gut 1974;15:139-42.

Chang C-S, Chen G-H, Lien H-C, et al. Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology 1998;28:1187-90.

Chesta J, Silva M,  Thompson L, et al. Bacterial overgrowth in small intestine in patients with liver cirrhosis. Rev Med Cil 1991;119:626-32.

Castiglione F, Rispo A, Di Girolamo, et al. Antibiotic treatment of small intestinal bacterial overgrowth in patients with Crohn’s disease. Aliment Pharmacol Ther 2003;18:1107-12.

Corazza GR, Menozzi MG, Strocchi A, et al. The diagnosis of small bowel bacterial overgrowth. Reliability of jejunal culture and inadequacy of breath hydrogen testing. Gastroenterology 1990;98:302-9.

Di Stefano M, Malservisi S, Veneto G, et al. Rifaximin versus chlortetracycline in the short-term treatment of small intestinal bacterial overgrowth. Aliment Pharmacol Ther 2000;14:551-6.

Donald IP, Kitchingmam G, Donald F, Kupfer RM. The diagnosis of small bowel bacterial overgrowth in elderly patients. J Am Geriatr Soc 1992;40:692-6.

Duchini A, Sessoms SL. Gastrointestinal hemorrhage in patients with systemic sclerosis and CREST syndrome. Am J Gastroenterol 1998;93:1453-6.

Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science. 2005;308:1635-8.

Elliott DE, Urban JFJ, Argo CK, Weinstock JV. Does the failure to acquire helminthic parasites predispose to Crohn's disease? FASEB J 2000;14:1848.

Elliott D, Li J, Blum B, et al. Exposure to Schistosome Eggs protects mice from TNBS-induced colitis. Am J Physiol 2003;284:G385.

Elphick DA, Chew TS, Higham SE, et al. Small bowel bacterial overgrowth in symptomatic older people: can it be diagnosed earlier? Gerontology 2005;51: 396-401.

Ferrucci L, Guralnik JM, Bandinelli S, et al. Unexplained anaemia in older persons is characterized by low erythropoietin and low levels of pro-inflammatory markers. Br J Haematol 2007;136:849-55.

Frayha RA, Shulman LE, Stevens MP. Hematological abnormality in scleroderma. A study of 180 cases. Acta Haematol 1980;64:25-30.

Fried M, Sliegrish H, Frei R, et al. Duodenal bacterial overgrowth during treatment with omeprazole in outpatients. Gut 1996;35:23-6.

Fukuhara K, Osugi H, Takada N, et al. Quantitative determinations of duodenogastric reflux, prevalence of Helicobacter pylori infection, and concentrations of interleukin-8. World J Surg 2003;27:567-70.

Funayama Y, Sasaki I, Naito H, et al. Monitoring and antibacterial treatment for post-operative bacterial overgrowth in Crohn’s disease. Dis Colon Rectum 1999;42:1072-7.

Goldblatt F, Gordon TP. Waterman S. Antibiody-mediated gastrointestinal dysmotility in scleroderma. Gastroenterology 2002;123:1144-50.

Haboubi NY, Montgomery RD. Small bowel bacterial overgrowth in elderly people: Clinical significance and response to treatment. Age Ageing 1992;21:13-9.

Hess SY, Zimmermann MB, Adou P, et al. Treatment of iron deficiency in goitrous children improves the efficacy of iodized salt in Côte d'Ivoire. Am J Clin Nutr 2002;75:743-8.

Husebye E, Skar V, Hoverstad T, et al. Fasting hypochlorhydria with gram positive gastric flora is highly prevalent in healthy old people. Gut 1992;33:1331-9.

Husebye E, Skar V, Hoverstad T, et al. Abnormal intestinal motor patterns explain enteric colonization with gram-negative bacilli in late radiation enteropathy. Gastroenterology 1995;109:1078-89.

Hutchinson S, Logan R. The effect of long-term omeprazole on the glucose-hydrogen breath test in elderly patients. Age Ageing 1997;26:87-90.

Giannella RA, Rout WR, Toskes PP. Jejunal brush border injury and impaired sugar and amino acid uptake in the blind loop syndrome. Gastroenterology 1974;67:965-74.

Jahraus CD, Bettenhausen D. A new paradigm in chemotherapy and radiotherapy-associated gastrointestinal toxicity: emerging evidence for small intestinal bacterial overgrowth as a contributing entity. Am J Gastroenterol 2006;110:A302.

Khan WI, Blennerhasset PA, Varghese AK, et al. Intestinal nematode infection ameliorates experimental colitis in mice. Infect Immun 2002;70:5931.

King CE, Toskes PP, Spivey JC, et al. Detection of small intestine overgrowth by means of a 14C-D-xylose breath test. Gastroenterology 1979;77:75-82.

Koshini R, Sun-Chuan D, Lescano S, Pimentel M. A systematic review of diagnostic testing for small intestinal bacterial overgrowth. Dig Dis Sci 2007; in press.

La Flamme, AC, Ruddenklau K, Backstrom BT. Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis. Infect Immun 2003;71:4996.

Laurentin EC, Lupasci A, Scarpellini E, et al. Small intestinal bacterial overgrowth prevalence in hypothyroidism. Gastroenterology 2005;128:W1743.

Lesniewska V, Rowland I, Laerke HN, et al. Relationship between dietary-induced commensal microflora and duodenojejunal myoelectric activity monitored by radiotelemetry in the rat in vivo. Exp Physiol 2006;91:229-37.

Levitt MD. Production and excretion of hydrogen gas in man. N Engl J Med 1969;281:122-7.

Levitt MD, Furne J, Springfield J, et al. Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa. J Clin Invest. 1999;104:1107-14.

Lewindon PJ, Robb TA, Moore DJ, et al. Bowel dysfunction in cystic fibrosis: Importance of breath testing. J Paediatr Child Health 1998;34:79-82.

Lewis SJ, Potts LF, Malhotra R, et al. Small bowel bacterial overgrowth in subjects living in residential care homes. Age Ageing 1999;28:181-5.

Lipski PS, Kelly PJ, Malhotra R. Mountford R. Small bowel bacterial overgrowth in subjects living in residential care homes. Age Aging 1992;21:5-12.

Lupasci A, Laurentin EC, Scarpellini E, et al. Small intestinal bacterial overgrowth prevalence in Parkinson’s disease. Gastroenterology 2005;128:W1742.

Mac Mahon M, Gibbons N, Mullins E, et al. Are hydrogen breath test valid in the elderly? Gerontology 1996;42:40-5.

Mack DR, Dhawan A, Kaufman SS, et al. Small bowel bacterial overgrowth as a cause of chronic diarrhea after liver transplantation in children. Liver Transpl Surg 1998;4:166-9.

Majewski M, Reddymasu SC, Sostarich S, et al. Efficacy of rifaximin, a nonabsorbed oral antibiotic, in the treatment of small intestinal bacterial overgrowth. Am J Med Sci 2007;333:266-70.

McEvoy A, Dutton J, James OF. Bacterial contamination of the small intestine is an important cause of occult malabsorption in the elderly. Br Med J 1983; 287:789-93.

Moreels TG, Nieuwendijk RJ, De Man JG, et al. Concurrent infection with Schistosoma mansoni attenuates inflammation induced changes in colonic morphology, cytokine levels, and smooth muscle contractility of trinitrobenzene sulphonic acid induced colitis in rats. Gut 2004;53:99.

Morencos G, de las Heras Castano G, Martin Ramos L, et al. Small bowel bacterial overgrowth in patients with alcoholic cirrhosis. Dig Dis Sci 1996;40:1252-6.

Pardo A, Bartoli R, Lorenzo-Zuniga V, et al. Effect of cisapride on intestinal bacterial overgrowth and bacterial translocation in cirrhosis. Hepatology 2000;31:858-63.

Parodi A, Resmini E, Greco A, et al. Small intestinal bacterial overgrowth in acromegalic patients. Presented at UEGW, Berlin 2006.

Pearson AJ, Brzechwa-Adjukiewicz A, et al. Intestinal pseudo-obstruction with bacterial overgrowth in the small intestine. Am J Dig Dis 1969;14:2000.

Parlesak A, Klein B, Schecher K, et al. Prevalence of small bowel bacterial overgrowth and its association with nutrition intake and nonhospitalized older adults. J Am Geriatr Soc 2003; 51:768-73.

Koshini R, Sun-Chuan D, Lezcano S, Pimentel M. A systematic review of testing for small intestinal bacterial overgrowth. Am J Gastroenterol 2007;102:Abstract 235.

Rhodes JM, Middleton P, Jewell DP. The lactulose hydrogen breath test as a diagnostic test for small bowel bacterial overgrowth. Scand J Gastroenterol 1979;14:333-6.

Riordan SM, McIver CJ, Wakefield D, et al. Mucosal cytokine production in small-intestinal bacterial overgrowth. Scand J Gastroenterol 1996;31:977-84.

Riordan S, McIver C, Duncombe V, et al. Factors influencing the 1-gram 14C-D-xylose breath test for bacterial overgrowth. Am J Gastroenterol 1995;90:1455-60.

Riordan SM, McIver CJ, Walker BM, et al. The lactulose breath hydrogen test and small intestinal bacterial overgrowth. Am J Gastroenterol 1996;91:1795-803.

Riordan SM, McIver CJ, Wakefield D, et al. Serum immunoglobulin and soluble IL-2 receptor levels in small intestinal overgrowth with indigenous gut flora. Dig Dis Sci 1999;44:939-44.

Riordan SM, McIver CJ, Wakefield D, et al. Small intestinal bacterial overgrowth in the symptomatic elderly. Am J Gastroenterol 1997;92:47-51.

Riordan SM, McIver CJ, Wakefield D, et al. Luminal immunity in small-intestinal bacterial overgrowth and old age. Scand J Gastroenterol 1996;31:1103-9.

Riordan SM, McIver CJ, Walker BM, et al. The lactulose hydrogen test and SIBO. Am J Gastroenterol 1996;91:1795-1809.

Romagnuolo J, Schiller D, Bailey RJ. Using breath tests wisely in a gastroenterology practice: an evidence-based review of indications and pitfalls in interpretation. Am J Gastroenterol 2002;97:1113-26.

Saltzman JR, Kowdley KV, Pedrosa MC, et al. Bacterial overgrowth without clinical malabsorption in elderly hypochlorhydric patients. Gastroenterology 1994;106:615-23.

Sekeroglu MR, Altun ZB, Algün E, et al. Serum cytokines and bone metabolism in patients with thyroid dysfunction. Adv Ther 2006;23:475-80.

Shindo K, Machida M, Fukumura M, et al. Omeprazole induces altered bile acid metabolism. Gut 1998;42:266-71.

Simren M, Stotzer P-O. Use and abuse of hydrogen breath tests. Gut 2006;55:292-303.

Smith GM, Chesner IM, Asquith P, et al. Small intestinal bacterial overgrowth in patients with chronic lymphocytic leukaemia. J Chin Pathol 1990;43:57-9.

Soudah HC, Hasler WL, Owyang C. Effect of octreotide on intestinal motility and bacterial overgrowth in scleroderma. N Engl J Med 1991;325:1461-7.

Suarez FL, Furne JK Springfield J, Levitt MD. Morning breath odor: influence of treatments and sulfur gases. J Dent Res 2000;79:1773-7.

Summers RW, Elliott DE, Qadir K, et al. Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Am J Gastroenterol 2003;98:2034.

Trespi E, Ferrieri A. Intestinal bacterial overgrowth during chronic pancreatitis. Curr Med Res Opin 1999;15:47-52.

Vanderhoof J, Young R. Use of probiotics in childhood and gastrointestinal disorders J Ped Gastroenterol Nutrition 1998;27:323-32.

Valdovinos M, Camilleri M, Thomforde G, et al. Reduced accuracy of 14C-D-xylose breath test for detecting bacterial overgrowth in gastrointestinal motility disorders. Scand J Gastroenterol 1993;28:963-8.

Valdovinos M, Camilleri M, Zimmerman BR. Chronic diarrhea in diabetes. Mechanism and approach to diagnosis and treatment. Mayo Clin Proc 1993;68:691-702.

Vantrappen G, Janssens J, Hellemans J, et al. The interdigestive motor complex of normal subjects and patients with bacterial overgrowth of the small intestine. J Clin Invest 1977;59:1158-66.

Varcoe R, Holliday D, Tavill A. Utilization of urea nitrogen for albumin synthesis in the stagnant loop syndrome. Gut 1974;15:898-902.

Verne GN, Eaker EY, Hardy E, et al. Effect of octreotide and erythromycin on idiopathic and scleroderma-associated intestinal pseudoobstruction. Dig Dis Sci 1995;40:1892-901. 

Virally-Monod M, Tielmans D, Kevorkian JP, et al. Chronic diarrhea and diabetes mellitus: Prevalence of small intestinal bacterial overgrowth. Diab Metab 1998;23:530-6.

Walmsley RS, Ayres RC, Pounder RE, Allan RN. A simple clinical colitis activity index. Gut 1998;43:29.

Yang C-Y, Chang C-S, Chen G-H. Small-intestinal bacterial overgrowth in patients with liver cirrhosis diagnosed with glucose H2 or CH4 breath tests. Scand J Gastroenterol 1998;33:867-71.

Bacterial overgrowth in irritable bowel syndrome

Atkinson W, Sheldon TA, Shaath N, et al. Food elimination based on IgG antibodies in IBS: A randomized controlled trial. Gut 2004;53:1459-64.

Barbara G. Mucosal barrier defects in irritable bowel syndrome. Who left the door open? Am J Gastroenterol 2006;101:1295-8.

Barbara G, Stanghellini V, De Giorgio R, et al. Functional gastrointestinal disorders and mast cells: implications for therapy. Neurogastroenterol Motil 2006;18:6-17.

Barbara G, Stanghellini V, Brandi G, et al. Interactions between commensal bacteria and gut sensorimotor function in health and disease. Am J Gastroenterol 2005;100:2560-8.

Bercík P, Wang L, Verdú EF, et al. Visceral hyperalgesia and intestinal dysmotility in a mouse model of postinfective gut dysfunction. Gastroenterology 2004;127:179-87.

Chadwick VS, Chen W, Shu D, et al. Activation of the mucosal immune system in IBS. Gastroenterology 2002;122:1778-83.

Chatterjee S, Park S, Low K, et al. The degree of breath methane production in IBS correlates to the severity of constipation. Am J Gastroenterol 2007;102:837-81.

Coelho AM, Fioramonti J, Bueno L. Systemic lipopolysaccharide influences rectal sensitivity in rats: role of mast cells, cytokines and vagus nerve. Am J Physiol Gastrointestinal Liver Physiol 2000;279:G781-G790.

Corazza GR, Menozzi MG, Strocchi A, et al. The diagnosis of small bowel bacterial overgrowth. Reliability of jejunal culture and inadequacy of breath hydrogen testing. Gastroenterology 1990;98:302.

Cuoco L, Salvagnini M. Small intestine bacterial overgrowth in irritable bowel syndrome: a retrospective study with rifaximin. Minerva Gastroenterol Dietol 2006;52:89-95.

Dinan TG, Quigley EMM, Ahmed SMM, et al. Hypothalamic-pituitary-gut axis dysregulation in IBS: plasma cytokines as a potential biomarker? Gastroenterology 2006;130:304-11.

Di Stefano M, Miceli E, Missanelli A, et al. Role of colonic fermentation in the perception of colonic distention in irritable bowel syndrome and functional bloating. Clin Gastroenterol Hepatol 2006;4:1242-7.

Di Stefano M, Malservisi S, Veneto G, et al. Xifaxan versus chlortetracycline in the short-term treatment of small intestinal bacterial overgrowth. Aliment Pharmacol Ther 2000;14:551-556.

Di Stefano M, Strocchi A, Malservisi S, et al. Non-absorbable antibiotics for managing intestinal gas production and gas-related symptoms. Aliment Pharmacol Ther 2000;15:1001-1008.

Di Stefano M, Vos R, Janssens J, et al. Effect of tegaserod, a 5-HT4 receptor partial agonist, on interdigestive and postprandial gastrointestinal motility in healthy volunteers. Gastroenterology 2003;DDW Abstract 105412.

Drossman DA, Richter JE, et al. Functional gastrointestinal disorders: Diagnosis, pathophysiology and treatment: a multinational consensus. Little Brown, 1994.

Dunlap SP, Jenkins, Neal KR, et al. Relative importance of enterchromaffin cell hyperplasia, anxiety, and depression in postinfectious IBS. Gastroenterology; 2003;125:1651-9.

Dunlap SP, Hebden J, Campbell E. Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes. Am J Gastroenterol 2006;101:1288-94.

DuPont HL, Jiang ZD, Okhuysen PC, et al. A randomized, double-blind, placebo-controlled trial of rifaximin to prevent travelers’ diarrhea. Ann Intern Med 2005;142:805-12.

Gonsalkorale WM, Perrey C, Pravica V, et al. Interleukin 10 genotypes in IBS: Evidence for an inflammatory component? Gut 2003;52:91-3.

Houghton LA, Lea R, Agrawal A, et al. Relationship of abdominal bloating to distention in irritable bowel syndrome and effect of bowel habit. Gastroenterology 2006;131:1003-10.

Husebye E, Hellstrom PM, Sundler F, et al. Influence of microbial species on small intestinal myoelectric activity and transit in germ free rats. Am J Physiol Gastrointest Liver Physiol 2001;280:G368-80.

Huang DB, DuPont HL. Rifaximin – a novel antimicrobial for enteric infections. J Infection 2005;50:97-106.

Hungin APS, Chang L, Locke GR, et al. Irritable bowel syndrome in the United States: prevalence, symptom patterns and impact. Aliment Pharmacol Ther 2005;21:1365-75.

Kalander K, Hatakka K, Poussa T, et al. A probiotic mixture alleviates symptoms in IBS patients: a controlled 6-month intervention. Aliment Pharmacol Ther 2005;22:387-94.

Koide A, Yamaguchi T, Odaka T, et al. Quantitative analysis of bowel gas using plain abdominal radiographs in patients with IBS. Am J Gastroenterol 2000;95:1735-41.

Lauritano EC, Gabrielli M, Lupascu A, et al. Rifaximin dose-finding study for the treatment of small intestinal bacterial overgrowth. Aliment Pharmacol Ther 2005;22:31-35.

Lee HR, Low K, Chatterjee S, et al. Rifaximin is superior to other antibiotics in treating and retreating bacterial overgrowth in IBS, supporting a lack of bacterial resistance development. Am J Gastroenterol 2006;110:A1224.

Lee HR, Low K, Chatterjee S, et al. In the treatment of IBS, the clinical response to rifaximin is determined by the normalization of the lactulose breath test. Am J Gastroenterol 2006;110:A1223.

Lewis MJV, Reilly B, Houghton LA, et al. Ambulatory abdominal wall plethysmography: Towards objective assessment of abdominal distension in IBS. Gut 2001;48:216-20.

Liebregts T, Adam B, Bredack C, et al. Immune activation in patients with irritable bowel syndrome. Gastroenterology 2007;132:913-20.

Lin HC, Pimentel M. Bacterial concepts in irritable bowel syndrome.  Reviews in Gastroenterological Disorders. 2005;5 (suppl 3):S1-S7. 

Lin HC, Prather C, Fisher RS, et al. Measurement of gastrointestinal transit. Dig Dis Sci 2005;50:989-1004.

Longstreth GF, Thompson WG, Chey WD,  et al. Functional bowel disorders.  Gastroenterology 2006;130:1480-91.

Lordal M, Hailstorm PM. Seratonin stimulates migrating myoelectric complex via 5-HT3 receptors dependent on cholinergic pathways in rat small intestine. Neurogastroenterol Mot 1999;11:1-10.

Lupascu A, Gabtielli M, Lauritano EC, et al. Hydrogen glucose breath test to detect SIBO: a prevalence case-control study in IBS. Aliment Pharmacol Ther 2005;22:1157-60.

Mailmen E, Ringtail T, Maeander K, et al. Analysis of the fecal microbiota of IBS patients and health controls with real-time PCR. Am J Gastroenterol 2005;100:373-82.

Marshall JK, Thabane M, Garg AX, et al. Incidence and epidemiology of irritable bowel syndrome after a large waterborne outbreak of bacterial dysentery. Gastroenterology 2006;131:445-50.

Marshall JK, Thabane M, Borgaonkar MR, James C. Postinfectious irritable bowel syndrome after a food-borne outbreak of acute gastroenteritis attributed to a viral pathogen. Clin Gastroenterol Hepatol 2007;5:457-60.

Nachamkin I. Chronic effects of Campylobacter infection. Microbes Infect. 2002;4:399-403.

Narwal S, Wetzler G, Molsky M. Rifaximin and IBS in the adolescent patients. Am J Gastroenterol 2007;102:Abstract 1073.

Neal KR, Barker L, Spiller RC. Prognosis in post-infective irritable bowel syndrome: a six year follow up study. Gut 2002;51:410-413.

Nobaek S, Johansson ML, Molin G, et al. Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with IBS. Am J Gastroenterol 2000;95:1231-8.

Nucera G, Gabrielli M, Lupascu A, et al. Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth. Aliment Pharmacol Ther 2005;21:1391-5.

O’Mahony L, McCarthy J, Kelly P, Hurley G, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology 2005;128:544-51.

Parry SD, Stansfield R, Jelley D, et al. Does bacterial gastroenteritis predispose people to functional gastrointestinal disorders? A prospective, community-based, case-control study. Am J Gastroenterol 2003;89:1970-5.

Perman JA, Molder S, Barr RG, et al. Fasting breath hydrogen concentration: normal values and clinical application. Gastroenterology 1984;87:1358-63.

Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome. Am J Gastroenterol 2000;95:3505-6.

Pimentel M, Soffer EE, Chow EJ, et al. Lower frequency of MMC is found in IBS subjects with abnormal lactulose breath test, suggesting bacterial overgrowth. Dig Dis Sci 2002;47:2639-43.

Pimentel M, Mayer AG, Park S, et al. Methane production during lactulose breath test is associated with gastrointestinal disease presentation.  Dig Dis Sci 2003;48:86-92.

Pimentel M, Chow EJ, Lin HC. Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. A double-blind, randomized, placebo-controlled study. Am J Gastroenterol 2003;98:412-419.

Pimentel M, Kong Y, Park S. IBS subjects with methane on lactulose breath test have lower postprandial serotonin levels than subjects with hydrogen. Dig Dis Sci 2004;49:84-7.

Pimentel M, Wallace D, Hallegua D, et al. A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing. Ann Rheum Dis 2004;63:450-452.

Pimentel M, Park S, Kane SV, et al. The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial.  Ann Intern Med 2006;145:557-63.

Pimentel M, Chatterjee S, Chang C, et al. Gastrointestinal infection with Camphylobacter jejuni 81-176 produces altered bowel function and bacterial overgrowth in rats. Am J Gastroenterol 2006;110:A1216.

Pimentel M, Lin HC, Enayati P, et al. Methane, a gas produced by enteric bacteria slows intestinal transit and augments small intestinal contractility. Am J Physiol 2006;290:G1089-95.

Pimentel M, Morales W, Lezcano S, et al. Nightly tegaserod prevents the clinical recurrence of bacterial overgrowth syndrome. Am J Gastroenterol 2007;102:Abstract 1038.

Plaza MA, Arruebo Murillo MD. Evidence for the involvement of 5-HT4 receptors in the 5-hydroxytrypamine-induced pattern of migrating myoelectric complex in sheep. Br J Pharmacol 1997;120:1144-50.

Plaza MA. 5-hydroxytrypamine and the gastrointestinal migrating myoelectric complex. Curr Opin Invest Drugs 2001;2:539-44.

Posserud I, Stotzer P, Bjornsson ER, et al. Altered counts of small bowel bacteria in patients with irritable bowel syndrome (IBS). Gastroenterology 2006. Abstract W1832.

Quigley EMM, Quera R. Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics. Gastroenterology 2006;130:S78-90.

Quigley EMM. From comic relief to real understanding; how intestinal gas causes symptoms. Gut 2003;52:1659-61.

Quigley EMM. Current concepts of the IBS. Scand J Gastroenterol 2003;38(S237):1-8.

Quigley EMM. Disturbances of motility and visceral hypersensitivity in IBS: Biological markers or epiphenomenon. Gastroenterol Clin North Am 2005;34:221-33.

Rhodes JM, Middleton P, Jewell DP. The lactulose hydrogen breath test as a diagnostic test for SIBO. Scand J Gastroenterol 1979;14:333-6.

Ritchie J. Pain from distension of the pelvic colon by inflating a balloon in the irritable bowel syndrome. Gut 1973;6:105-112.

Riordan SM, McIver CJ, Wakefield D, et al. Mucosal cytokine production in small intestinal bacterial overgrowth. Scand J Gastroenterol 1996;31:977-84.

Riordan SM, McIver CJ, Thomas DH, et al. Luminal bacteria and small-intestinal permeability. Scand J Gastroenterol 1997;32:556-63.

Salvioli B, Serra J, Azpiroz F, Malagelada JR. Impaired small bowel gas propulsion in patients with bloating during intestinal lipid infusion. Am J Gastroenterol 2006;101:1853-7.

Sen S, Dear KL, King TS, et al. Evaluation of hydrogen excretion after lactulose administration as a screening test for causes of irritable bowel syndrome. Eur J Gastroenterol Hepatol 2002;14:753-6.

Serra J, Azpiroz F, Malagelada J-R. Impaired transit and tolerance of intestinal gas in the IBS. Gut 2001;48:14-9.

Sewell DZ, Qing Z, Reinke E, et al. Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova immunization. Int Immunol 2003;15:59.

Sharara AI, Aoun E, Abdul-Baki H, et al. A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence. Am J Gastroenterol 2006;101:326-33.

Soyturk M, Akpinar H, Gurler O, et al. Irritable bowel syndrome in persons who acquired trichinellosis. Am J Gastroenterol 2007;102:1064-9.

Spiller R. Probiotics: an ideal anti-inflammatory treatment for IBS? [Editorial] Gastroenterology 2005;128:783-5.

Spiller RC, Jenkins D, Thornley JP, et al. Increased mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Camphylobacter enteritis and in post-dystenteric IBS. Gut 2000;47:804-11.

Troeger H, Epple HJ, Schneider T, et al. Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in the human duodenum. Gut 2006;Aug 25.

Tornblom H, Lindberg G, Nyberg B, Veress B. Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome. Gastroenterology 2002;123:1972-9.

Van der Veek P, DeKoon Y, van den Berg M, et al. Tumor necrosis factor alpha and interleukin 10 gene polymorphisms in irritable bowel syndrome. Gastroenterology 2005;126:A52.

Vernia P, Camillo MD, Marinaro V, Caprilli R. Effect of predominant methanogenic flora on the outcome of lactose breath test in IBS patients. Eur J Clin Nutr 2003;57:1116-9. 

Weinstock LB, Tordorczuk JT, Fern SE, et al. Comprehensive SIBO therapy of IBS patients. Am J Gastroenterol 2006;110:A1123.

Weinstock LB, Tordorczuk JT, Fern SE, et al. Comprehensive SIBO therapy of functional bowel patients. Am J Gastroenterol 2006;110:A1124.

Weston AP, Biddle WL, Bhatia PS, et al. Terminal ileal mucosal mast cells in irritable bowel syndrome. Dig Dis Sci 1993;38:1590-5.

Whorwell PJ. The problem of gas in IBS. Am J Gastroenterol 2000;95:1618-9.

Whorwell PJ, Altringer L, Morel J, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with IBS. Am J Gastroenterol 2006;101:1581-90.

Yang J, Lee HR, Low K, et al. Rifaximin versus other antibiotics in the primary treatment and retreatment of bacterial overgrowth in IBS. Dig Dis Sci 2007 (in press).

Bacterial overgrowth in IBS-overlap conditions

Aaron LA, Buchwald D. A review of the evidence for overlap among unexplained clinical conditions. Ann Intern Med 2001;134:868-81.

Alagiri M, Chottiner S, Rutner V, et al. Interstitial cystitis: unexplained associations with other chronic diseases and pain syndromes. Urology 1997; 49: S52-7.

Bach JF. Infections and autoimmune diseases. J Autoimmune 2005;25:74-80.

Barbara GM, Stanghellini, De Giorgio R, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology 2004;126:693-702.

Blackburn-Munro G. Hypothalamus-pituitary-adrenal axis dysfunction as a contributory factor to chronic pain and depression. Curr Pain Headache Rep 2004;8:116-24.

Bocholt SF, Harbor MS, Blackburn-Munro G, et al. Involvement and role of the hypothalamus-pituitary-adrenal (HPA) stress axis in animal models of chronic pain and inflammation. Stress 2004;7:1-14.

Days CV, Nu Y, Bullet KM, Day TA. Effects of chronic estrogen replacement on stress-induced activation of hypothalamic-pituitary-adrenal axis control pathways. J Neuroendocrinol 2000;12:784-94.

Facchinetti F, Fioroni L, Martignoni E, et al. Changes of opioid modulation of the hypothalamo-pituitary-adrenal axis in patients with severe premenstrual syndrome. Psychosom Med 1994;56:418-22.

Giamberardino M. Sex-related and hormonal modulation of visceral pain.  In R. Fillingim (Ed.), Sex gender and pain (Vol. 17), Seattle, WA: IASP Press.

Grinevich V, Ma XM, Herman JP, Jezova D, et al. Effect of repeated lipopolysaccharide administration on tissue cytokine expression and hypothalamic-pituitary-adrenal axis activity in rats. J Neuroendocrinol. 2001;13:711-23.

Hadid R, Spinedi E, Chautard T, et al. Role of several mediators of inflammation on the mouse hypothalamo-pituitary-adrenal axis response during acute endotoxemia. Neuroimmunomodulation 1999;6:336-43.

Henningsen P, Zimmermann T, Sattel H. Medically unexplained physical symptoms, anxiety, and depression: a meta-analytic review. Psychosom Med. 2003;65:528-33.

Hill MR, Clarke S, Rodgers K, Thornhill B, et al. Effect of peroxisome proliferator-activated receptor alpha activators on tumor necrosis factor expression in mice during endotoxemia. Infect Immun 1999;67:3488-93.

King TS, Elia M, Hunter JO. Abnormal colonic fermentation in IBS. Lancet 1998;352:1187-9.

Kirschbaum C, Kudielka BM, Gaab J, et al. Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. Psychosom Med 1999;61:154-62.

Korszun A, Papadopoulos E, Demitrack M, et al. The relationship between temporomandibular disorders and stress-associated syndromes. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86:416-20.

Lin HC. Small intestinal bacterial overgrowth: a framework for understanding irritable bowel syndrome. JAMA 2004;292:852-8.

Pezzone MA, Liang R, Fraser MO. A model of neural cross-talk and irritation in the pelvis: implications for the overlap of chronic pelvic pain disorders. Gastroenterology 2005;128;1953-4.

Prior A, Wilson K, Whorwell PJ, et al. Irritable bowel syndrome in the gynecology clinic. Survey of 798 new referrals. Dig Dis Sci 1989;34:1820-4.

Rotem AY, Sper, Krugliak P, et al. Polypsomnographic and actigraphic evidence of sleep fragmentation in patients with IBS. Sleep 2003;26:74-52.

Smolen JS, Maini RN. Interleukin-6: a new therapeutic target. Arthritis Res Ther 2006;8 (Suppl 2):S5.

Sperber AD, Alzmon Y, Neumann L, et al. Fibromyalgia in the irritable bowel syndrome: studies of prevalence and clinical implications. Am J Gastroenterol 1999;94:3541-6.

Valles A, Marti O, Harbuz MS, Armario A. A single lipopolysaccharide administration is sufficient to induce a long-term desensitization of the hypothalamic-pituitary-adrenal axis. Neuroscience. 2002;112:383-389.

Veale D, Kavanagh G, Fielding JF, et al. Primary fibromyalgia and the irritable bowel syndrome: different expressions of a common pathogenetic process. Br J Rheumatol 1991;30:220-2.

CPPS – Chronic Pelvic Pain Syndrome

     Interstitial Cystitis

Abrams P, Cardozo L, Fall M, Griffiths D, et al. The standardization of terminology of lower urinary tract function: report form Standardization Subcommittee of the International Continence Society. Neurourol Urodyn 2002;21:167-78.

Ahmed. Urinary bladder permeability and mast cell migration in TNBS colitis. Am J Gastroenterol 2006;110:A1255.

Anderson KE.  Bladder activation: afferent mechanisms. Urology 2002;59(5S1):43-50.

Attene-Ramos MS, Wagner ED, et al. Evidence that hydrogen sulfide is a genotoxic agent. Mol Cancer Res 2006;4:9-14.

Bouchelouche K, Nordling J, Hald T, Bouchelouche P. The cysteinyl leukotriene D4 receptor antagonist montelukast for the treatment of interstitial cystitis. J Urol 2001;166:1734-7.

Bouchelouche K, Kristensen B, Nordling J, et al. Increased urinary leukotriene E4 and eosinophil protein X excretion in patients with interstitial cystitis. J Urol 2001;166:2121-5.

Boucher W, el-Mansoury M, Pang X, Sant GR, Theoharides TC.  Elevated mast cell tryptase in the urine of patients with interstitial cystitis. Br J Urol 1995;76:94-100. 

Buffington CA, Pacak K. Increased plasma norepinephrine concentration in cats with interstitial cystitis. J Urol 2001;165:2051-4.

Burkhard FC, Blick N, Hochreiter WW, Studer UE.  Urinary urgency and frequency, and chronic urethral and/or pelvic pain in females.  Can doxycycline help? J Urology

2004;172(1):232-5.

Chahl LA. Hydrogen sulphide: an endogenous stimulant of capsaicin-sensitive primary afferent neurons? Br J Pharmacol 2004;142:1-2.

Chiang G, Patra P, Letourneau R, Jeudy S, Boucher W, Green M, Sant GR, Throharides TC. Pentosanpolysulfate (Elmiron) is a potent inhibitor of mast cell histamine secretion.  Adv Exp Med Biol 2003:539:713-29.

Christmas TJ, Holmes SA, Hendry WF. Bladder replacement by ileocystoplasty: the final treatment for interstitial cystitis. Br J Urol 1996;78:69-73.

Curhan GC, Speizer FE, Hunter DJ, et al. Epidemiology of interstitial cystitis: a population based study. J Urol 1999;161:549-52.

Domingue GJ, Ghoniem GM, Bost KL, et al. Dormant microbes in interstitial cystitis. J Urol 1995;153:1321-6.

Durier JL. Anti-anaerobic antibiotic use in chronic inflammation, urgency, frequency, urge incontinence and in interstitial cystitis syndromes. Presented at meeting of Women’s Urological Health Program, National Institute of Diabetes, Digestive, and Kidney Diseases Research Symposium on Interstitial Cystitis, Bethesda, Maryland, January 9-11, 1995.

Erickson DR, Tomaszewski JE, Kunselman AR, et al. Do the National Institute of Diabetes and Digestive and Kidney Diseases cystoscopic criteria associate with other clinical and objective features of interstitial cystitis? J Urol 2005;173:93-7.

Fitzgerald MP, Koch D, Senka J.  Visceral and cutaneous sensory testing in patients with painful bladder syndrome.  Neurourol Urodyn 2005;24:627-32.

Giamberardino M. Sex-related and hormonal modulation of visceral pain. In R. Fillingim (Ed.), Sex gender and pain (Vol. 17), Seattle, WA: IASP Press, 2000.

Gillenwater JY, Wein AJ. Summary of the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases Workshop on Interstitial Cystitis, National Institutes of Health, Bethesda, Maryland, August 28-29, 1987. J Urol 1988;140:203-6.  

Ghoniem GM, El Leithy T, Domingue G. Antimicrobial treatment for interstitial cystitis: preliminary report. Presented at Partnership for Progress: Interstitial Cystitis Scientific Workshop, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Interstitial Cystitis Association, San Diego, CA, October 5-6, 1995.

Haarala M, Jalava, J, Laato, M, et al. Absence of bacterial DNA in the bladder of patients with interstitial cystitis. J Urol 1996;156:1843-5.

Haarala M, Kiiholma P, Lehtonen OP. Urinary bacterial flora of women with urethral syndrome and interstitial cystitis. Gynecol Obstet Invest 1999;47:42-4.

Hampson SJ, Christmas TJ, Moss MT. Search for mycobacteria in interstitial cystitis using mycobacteria specific DNA probes with signal amplification by polymerase chain reaction. Br J Urol 1993;72:303-6.

Hanno PM, Landis JR, Matthews-Cook Y, et al. The diagnosis of interstitial cystitis revisited: lessons learned from the National Institutes of Health Interstitial Cystitis Database study. J Urol 1999;161:553-7.

Hanno P, Levin RM, Monson FC, et al. Diagnosis of interstitial cystitis. J Urol 1990;143:278-81.

Harrington DS, Fall M, Johansson SL. Interstitial cystitis: bladder mucosa lymphocyte immunophenotyping and peripheral blood flow cytometry analysis.  J Urol 1990;144:868-71.

Hedelin HH, Mardh PA, Brorson JE, et al. Mycoplasma hominis and interstitial cystitis. Sex Transmitted Dis 1983;10:327-30. 

Hukkanen V, Haarala M, Nurmi M, et al. Viruses and interstitial cystitis: adenovirus genomes cannot be demonstrated in urinary bladder biopsies. Urol Res 1996;24:235-8.

Keay S, Schwalbe RS, Trifillis AL, et al. A prospective study of microorganisms in urine and bladder biopsies from interstitial cystitis patients and controls. Urology 1995;45:223-9.

Keay S, Warren JW. Is interstitial cystitis an infectious disease? Int J Antimicrob Agents 2002;19:480-3.

Kisman OK, Lycklama à Nijeholt AA, van Krieken JH. Mast cell infiltration in intestine used for bladder augmentation in interstitial cystitis. J Urol 1991;146:1113-4.

Koziol JA, Clark DC, Gittes RF, Tan EM. The natural history of interstitial cystitis: a survey of 374 patients. J Urol 1993;149:465-9.

Kusek JW, Nyberg LM. The epidemiology of interstitial cystitis: is it time to expand our definition? Urology 2001;57:95-9.

Kushner L, Chiu PY, Brettschneider N, et al. Urinary substance P concentration correlates with urinary frequency and urgency in interstitial cystitis patients treated with intravesical dimethyl sulfoxide and not intravesical anesthetic cocktail. Urology 2001;57(6 S1):129.

Larsen S, Thompson SA, Hald T, et al. Mast cells in interstitial cystitis. Br J Urol 1982;54:283-6.

Lutgendorf SK, Kreder KJ, Rothrock NE, et al. Diurnal cortisol variations and symptoms in patients with interstitial cystitis. J Urol 2002;167:1338-43.

Nelson H, Kemp J, Berger W, et al. Efficacy of zileuton controlled-release tablets administered twice daily in the treatment of moderate persistent asthma: a 3-month randomized controlled study. Ann Allergy Asthma Immunol 2007;99:178-84.
Nickel JC. Interstitial cystitis: a chronic pelvic pain syndrome. Med Clin North Am 2004;88:467-81, xii.

Norden CW, Green GM, Kass EH. Antibacterial mechanisms of the urinary bladder. J Clin Invest 1968;47:2689-2700.

Nordling J. Interstitial cystitis: how should we diagnose it and treat it in 2004? Curr Opin Urol 2004;14:323-7.

O’Leary MP, Sant GR, Fowler FJ, Jr, et al. The interstitial cystitis symptom index and problem index. Urology 1997;49(S):58-63.

Pang X, Boucher W, Triadafilopoulos G, et al. Mast cell and substance P-positive nerve involvement in a patient with both irritable bowel syndrome and interstitial cystitis. Urology 1996;47:436-8.

Parsons CL, Stauffer C, Schmidt JD. Bladder-surface glycosaminoglycans: an efficient mechanism of environmental adaptation. Science 1980;208:605-7.

Parsons CL, Housley T, Schmidt JD, et al. Treatment of interstitial cystitis with intravesical heparin. Br J Urol 1994;73:504-7.

Parsons CL, Dell J, Stanford EJ, et al. Increased prevalence of interstitial cystitis: previously unrecognized urologic and gynecologic cases identified using a new symptom questionnaire and intravesical potassium sensitivity. Urology 2002;60:573-8.

Patacchini R, Santicioli P, Giuliani S, et al. Pharmacological investigation of hydrogen sulfide (H2S) contractile activity in rat detrusor muscle. Eur J Pharmaco 2005;509:171-7.

Patacchini R, Santicioli P, Giuliani S, et al. Hydrogen sulfide (H2S) stimulates capsaicin-sensitive primary afferent neurons in the rat urinary bladder. Br J Pharmacol 2004;142:31-4.

Peeker R, Fall M. Toward a precise definition of interstitial cystitis: further evidence of differences in classic and nonulcer disease. J Urol 2002;167:2470-2.

Peters KM, Diokno AC, Steinert BW. Preliminary study on urinary cytokine levels in interstitial cystitis: does intravesical bacille Calmette-Guerin treat interstitial cystitis by altering the immune profile in the bladder? Urology 1999;54(3):450-3.

Rovner E, Propert KJ, Bresinger C, et al. Treatments used in women with interstitial cystitis: The Interstitial Cystitis Data Base (ICDB) study experience. The Interstitial Cystitis Data Base Study Group. Urology 2000;56:940-5.

Sant GR, Propert KJ, Hanno PM, et al. A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis. J Urology 2003;170:810-5.

Sant GR, Theoharides TC. The role of the mast cell in interstitial cystitis. Urol Clin North Am 1994;21(1):41-53. 

Singh G, Thomas DG. Interstitial cystitis: involvement of the intestine. Eur Urol 1996;29:322-4.

Sirinian E, Azevedo K, Payne CK. Correlation between 2 interstitial cystitis symptom instruments. J Urology 2005;173:835-40.

Simon LJ, Landis JR, Erickson DR, et al. The interstitial cystitis data base study: Concepts and preliminary baseline descriptive statistics. Urology 1997;49(S5A): 64-75. 

Summary of the National Institute of Arthritis, Diabetes, Digestive, and Kidney Diseases Workshop on Interstitial Cystitis, National Institutes of Health, Bethesda, Maryland, August 28-29, 1987. J Urology 1988;140:203-6.