Acute Food Poisoning: Possible Trigger for a Variety of Chronic GI Disorders

 In Gastrointestinal, Toxicology

Tolle Causam

Steven Sandberg-Lewis, ND, DHANP

A standard question I ask when taking a history of a patient with celiac disease, inflammatory bowel disease (IBD), or irritable bowel syndrome (IBS) is: “What is your lifetime history of food poisoning, traveler’s diarrhea, or gastroenteritis?” I may already have the clue if they report that they have never been well since a severe bout with Salmonella or Shigella. In other cases, a brief case of diarrhea, abdominal cramps, and vomiting is not remembered years later, so I have to clarify that even a transient digestive upset such as this can be a trigger for post-infectious IBS or celiac disease. In contrast to the “never well since” cases, it may take years after an acute illness for the chronic gastrointestinal (GI) problems to start.

Celiac Disease

Riddle et al published a study in 2012 that researched the odds ratios for the onset of celiac disease after viral and non-viral (bacterial or parasitic) gastroenteritis.1 They studied a US military population and found that a history of any infectious gastroenteritis (referred to as IGE in the journal article) doubled the risk of developing celiac disease (Table 1). Viral causes of acute diarrhea had about half the risk compared to those with bacterial or parasitic etiology. The strongest effect was celiac disease onset within 2 years of a non-viral gastroenteritis. It is known that those with genetic markers for celiac disease may be asymptomatic for many decades before the onset of clinical symptoms. IGE may be one of the significant triggers converting a mild or asymptomatic case into one with clinical manifestations.

Table 1. Celiac Disease Incidence Following Infectious Gastroenteritis1

Timing of Gastroenteritis (IGE) Odds Ratio
Any prior IGE 2.06
Any prior non-viral IGE 3.27
Any prior viral IGE 1.44
2 years prior IGE 2.93
2 years prior non-viral IGE 6.65
2 years prior viral IGE 1.57

(Data based on a healthy US adult population of active-duty military personnel)

IBS / Post-Infectious IBS

In a similar fashion, irritable bowel syndrome may be triggered by acute GI infections. This is typically the diarrhea type of IBS, and the classic organism is Campylobacter. In a recent study of 747 subjects, 13.8% developed post-infectious IBS (PI-IBS). Biopsies revealed higher enterochromaffin cell counts and significantly higher mucosal T-lymphocytes of the lamina propria in patients with PI-IBS compared to healthy volunteers.2 Recall that enterochromaffin cells produce secretin, cholecystokinin, and serotonin. Serotonin’s many functions include modulation of appetite, motility, fluid secretion, and digestive enzyme release.3 Additional research has revealed that patients with PI-IBS have increased levels of the inflammatory mediator, interleukin-1β.4

As noted above, increased numbers of intraepithelial lymphocytes are found in rectal biopsy specimens from patients with PI-IBS. This general immune finding is also seen in various tissues in patients with celiac disease and microscopic colitis.5 T-lymphocytes and mast cells are the predominant cells in these biopsies. Mast cell infiltrates are especially likely in the terminal ileum and cecum.6 A New Zealand study found a nearly 3-fold increase in mast cells in colonocytes of IBS patients compared to controls, as well as increased numbers of actively degranulating mast cells.7 Also noted was increased release of tryptase and histamine, both of which may sensitize afferent neurons, causing pain or hypersensitivity.

An Autoimmune Mechanism for PI-IBS

Post-infectious IBS has been shown to have an autoimmune etiology in both murine and human studies. Infectious gastroenteritis is the most significant environmental risk factor for IBS.8 Organisms that trigger PI-IBS include Campylobacter,9 Salmonella,9 Shigella,9 Escherichia coli,9 viruses,10 and Giardia.11

Cytolethal distending toxin (CDT) is produced by enteric pathogens that cause PI-IBS. Campylobacter jejuni is the prototypical bacteria that produces CDT.12 Other bacteria that produce CDT include Haemophilus ducreyi (chancroid), Aggregatibacter actinomycetemcomitans (periodontitis), E coli (traveler’s diarrhea), Shigella dysenteriae (dysentery), Salmonella enterica (typhoid fever), and Campylobacter upsaliensis (enterocolitis).

The interstitial cells of Cajal (ICC) are fibroblast-like cells that act as pacemakers for the migrating motor complex (MMC). A key underlying cause of PI-IBS is thought to be deficiency of the MMC, which moves debris and bacteria down into the large intestine during fasting at night and between meals.13 Post-infectious, diarrhea-predominant IBS is associated with small intestine bacterial overgrowth (SIBO).14 In various studies, frequency of SIBO among patients presenting with IBS varied from 4% to 78%, depending on the type of testing used and IBS type (diarrhea, constipation, or mixed type). If the diarrhea-predominant type is isolated, the correlation with SIBO is higher.14

The number of ICCs is reduced in post-Campylobacter jejuni gastroenteritis-infected rats that eventually develop bacterial overgrowth.12 Three months after C jejuni gastroenteritis, 27% of rats had SIBO. Compared to controls, these rats had a lower number of ICCs in the jejunum and ileum (0.12 ICC/villus was the threshold for establishing SIBO.) Other rat studies suggest that the CDT toxin may destroy the interstitial cells of Cajal by stimulating the production of autoantibodies against a cytoskeletal protein known as vinculin.15,16 The antigen-antibody complexes between anti-vinculin antibodies and CDT lead to autoimmune destruction of ICCs.

Living in unsanitary conditions, with frequent exposure to food- and water-borne pathogens is a likely cause of SIBO in children in the developing world. In 90 Bangladeshi 2-year-olds from impoverished neighborhoods, SIBO was significantly related to growth stunting and living near an open sewer.17 Through personal communication with the author of this study, I learned that an open sewer is common in these areas. Running along the perimeter of the housing units are shallow-flowing conduits containing household waste. Author Dr Donowitz explained that the children are told to never touch the flowing sewage, but if their only toy falls into the conduit, they will reach in and retrieve it. It was found that 16.7% of the children in these communities had hydrogen-associated SIBO based on glucose breath-testing. Growth stunting in SIBO was found to be associated with reduced cognitive development as well as an increased risk of death prior to 5 years of age.17

Of interest, 40% of patients with IBS have colonic biopsies indicative of a non-specific microscopic colitis.18

Inflammatory Bowel Disease

A Spanish population-based study found a hazard ratio of 2.4 for developing IBD within a year of experiencing a bout of gastroenteritis, compared to controls.19 This was especially true for Crohn’s disease, as opposed to ulcerative colitis. The increased incidence of Crohn’s vs ulcerative colitis also follows antibiotic and NSAID use. A meta-analysis found that Campylobacter species, especially C concisus, increased the risk of developing IBD (odds ratio [OR]=3.76).20 C showae had a 2.39 OR for increased IBD risk.

A nationwide case-controlled study in Sweden compared 44 215 IBD patients with 436 507 controls.21 Seven percent of IBD patients had a history of previous gastroenteritis, as compared with 4.1% of the control subjects. Higher risk of IBD cases was associated with any previous GI infection (OR=1.64), bacterial GI infection (OR=2.02), parasitic GI infection (OR=1.55), or viral GI infection (OR=1.55). Compared to controls, ulcerative colitis patients showed higher odds of having had a previous Salmonella, E coli, Campylobacter, or C difficile infection. Crohn’s patients had higher odds of having had a previous Salmonella, Campylobacter, Yersinia enterocolitica, C difficile, amoebic, or norovirus infection compared to controls. In addition, greater numbers of gastroenteritis episodes increased the risk of IBD, and this risk remained elevated for more than 10 years (OR=1.26).21

Rather than being mutually exclusive, IBD and IBS often coexist in patients.22 Perhaps this is why dietary interventions are often successful in both IBS and IBD. A crossover trial showed that a low-FODMAPs diet produced benefit in IBS23 A retrospective survey also suggested benefit of a low-FODMAPs diet for patients with IBD symptoms resistant to immunosuppressive medications.24 Larger-scale, randomized controlled trials are warranted.

Colon Cancer

There is little available evidence for developing colon cancer following food poisoning; however, some initial population-based research has been published. A study of 14 264 Dutch residents examined the relationship between a history of Salmonella infection and risk of developing colon cancer. Ninety-eight cases of colorectal cancer (CRC) were associated with Salmonella infection history, and the risk was higher with Salmonella enteriditis species and with diagnosis of CRC prior to age 60.25 Factored into the analysis were age, gender, latency, socioeconomic status, genetic predisposition, and the presence of IBD. These neoplasms were most commonly in the ascending and transverse colon. On a positive note, these cancers were mostly low-grade.

References:

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  2. Hellström PM. Pathophysiology of the irritable bowel syndrome – Reflections of today. Best Pract Res Clin Gastroenterol. 2019;40-41:101620.
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  4. Gwee KA, Collins SM, Read NW, et al. Increased rectal mucosal expression of interleukin-1β in recently acquired post-infectious irritable bowel syndrome. Gut. 2003;52(4):523-526.
  5. Spiller RC, Jenkins D, Thornley JP, et al. Increased rectal mucosal enteroendocrine cells, T-lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut. 2000;47(6):804-811.
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  14. Ghoshal UC, Kumar S, Mehrotra M, et al. Frequency of small intestinal bacterial overgrowth in patients with irritable bowel syndrome and chronic non-specific diarrhea. J Neurogastroenterol Motil. 2010;16(1):40-46.
  15. Sung J, Morales W, Kim G, et al. Effect of repeated Campylobacter jejuni infection on gut flora and mucosal defense in a rat model of post infectious functional and microbial bowel changes. Neurogastroenterol Motil. 2013;25(6):529-537.
  16. Pimentel M, Morales W, Pokkunuri V, et al. Autoimmunity Links Vinculin to the Pathophysiology of Functional Bowel Changes Following Campylobacter jejuni Infection in a Rat Model. Dig Dis Sci. 2014;60(5):1195-1205.
  17. Donowitz JR, Haque R, Kirkpatrick BD, et al. Small Intestine Bacterial Overgrowth and Environmental Enteropathy in Bangladeshi Children. MBio. 2016;7(1):e02102-e02115.
  18. Chadwick VS, Chen W, Shu D, et al. Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology. 2002;122(7):1778-1783.
  19. García Rodríguez LA, Ruigómez A, Panés J. Acute Gastroenteritis is followed by an increased risk of Inflammatory Bowel Disease. Gastroenterology. 2006;130(6):1588-1594.
  20. Castaño-Rodríguez N, Kaakoush NO, Lee WS, Mitchell HM. Dual role of Helicobacter and Campylobacter species in IBD: a systematic review and meta-analysis. Gut. 2017;66(2):235-249.
  21. Axelrad JE, Olén O, Askling J, et al. Gastrointestinal Infection Increases Odds of Inflammatory Bowel Disease in a Nationwide Case-Control Study. Clin Gastroenterol Hepatol. 2019;17(7):1311-1322.e7.
  22. Spiller R, Major G. IBS and IBD – separate entities or on a spectrum? Nat Rev Gastroenterol Hepatol. 2016;13(10):613-621.
  23. Anderson JL, Hedin CR, Benjamin JL, et al. Dietary intake of inulin-type fructans in active and inactive Crohn’s disease and healthy controls: a case-control study. J Crohns Colitis. 2015;9(11):1024-1031.
  24. Staudacher HM, Lomer MC, Anderson JL, et al. Fermentable carbohydrate restriction reduces luminal bifidobacteria and gastrointestinal symptoms in patients with irritable bowel syndrome. J Nutr. 2012;142(8):1510-1518.
  25. Mughini-Gras L, Schaapveld M, Kramers J, et al. Increased colon cancer risk after severe Salmonella infection. PLoS One. 2018;13(1):e0189721.

Steven Sandberg-Lewis, ND, DHANP, has been a practicing naturopathic physician for over 40 years after graduating from NCNM. Since 1996 he has taught gastroenterology and GI physical medicine at NUNM. His private practice is at Hive Mind Medicine in Portland, OR. Dr Sandberg-Lewis is a popular international lecturer, and is frequently interviewed about GI health and disease. He is the author of the Townsend Letter column, “Functional Gastroenterology Bolus,” as well as the textbook, Functional Gastroenterology: Assessing and Addressing the Causes of Functional Digestive Disorders. In 2010 he co-founded the SIBO Center at NUNM.

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