Food Poisoning - The Gift That Keeps on Giving
STEVEN SANDBERG-LEWIS
N.D., DHANP
A standard question I ask when taking a history of a patient with celiac disease, inflammatory bowel disease or irritable bowel syndrome 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, years later a brief case of diarrhea, abdominal cramps and vomiting is not remembered, 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 the acute illness for the chronic GI problems to start.
Celiac Disease
Riddle, MS 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. 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.
Irritable Bowel Syndrome/Post Infectious Irritable Bowel Syndrome
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 mucosal T lymphocytes of the lamina propria were significantly higher 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 finds 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 of patients with PI-IBS. This general immune finding is also seen in various tissues in patients with celiac disease and microscopic colitis. T lymphocytes and mast cells are the predominant cells in these biopsies.[5] 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 IBS patients compared to controls as well as increased numbers of actively degranulating mast cells. Also noted were increased release of tryptase and histamine both of which may sensitize afferent neurons causing pain or hypersensitivity.[7]
An Autoimmune Mechanism for PI-IBS
Post-infectious IBS (PI-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, Salmonella, Shigella, E. 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), Escherichia 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 post-infectious 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). 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 interstitial cells of Cajal (ICCs) are reduced in post Campylobacter jejuni gastroenteritis infected rats that eventually develop bacterial overgrowth (Pokkunuri V, 2012.) Three months after C. jejuni gastroenteritis, 27% of rats had SIBO. These rats had a lower number of interstitial cells of Cajal (ICC) than controls in the jejunum and ileum (0.12 ICC/villus was the threshold for developing SIBO.) CDT toxin may destroy the interstitial cell of Cajal by stimulating the production of autoantibodies against a cytoskeletal protein known as vinculin. The antigen-antibody complexes between anti-vinculin antibodies and cytolethal distending toxin lead to autoimmune destruction of interstitial cells of Cajal.[15, 16]
Living in unsanitary conditions with frequent exposure to food and water-borne infection 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. 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. 16.7% of the children in these communities had hydrogen 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. Additionally 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 the hazard ratio of IBD was 2.4 within a year of experiencing a bout of gastroenteritis compared to controls 19. This was especially true for Crohn’s rather than 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 had an odds ratio of 3.76 for IBD. C. showae had a 2.39 odds ratio of increased IBD risk 20.
A nationwide case controlled study in Sweden compared 44,215 IBD patients against 436,507 controls. 7.0% of IBD patients had a record of previous gastroenteritis compared with 4.1% of the control subjects 21. The IBD cases had higher odds for any previous gastrointestinal infection (OR, 1.64), bacterial gastrointestinal infection (OR, 2.02), parasitic gastrointestinal infection (OR, 1.55), and viral gastrointestinal infection (OR, 1.55). Ulcerative colitis patients had higher odds of having had a previous Salmonella, E. coli, Campylobacter or C. difficile infection compared to controls. 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 odds of IBD, and the risk remained elevated for more than 10 years (OR, 1.26).
Rather than being mutually exclusive, inflammatory bowel disease and irritable bowel syndrome often co-exist in patients 22. Perhaps this is why dietary interventions have shown success in both IBS and IBD. A crossover trial low FODMAPs diet produced benefit in IBS 23. A retrospective survey also suggested benefit of a low FODMAP diet for patients with IBD symptoms resistant to immunosuppression, so larger scale randomized controlled trials are warranted 24.
Colon Cancer
There is little available evidence for colon cancer following food poisoning, but initial population based research has been published. A study of 14,264 Dutch residents examined the relationship between history of Salmonella infection and risk of developing colon cancer. 98 cases of colorectal cancer (CRC) were associated with Salmonella 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 inflammatory bowel disease. These neoplasms were most commonly in the ascending and transverse colon. On a positive note, these cancers were mostly low grade.
References:
1. Riddle MS, Murray JA, Porter CK, The incidence and risk of celiac disease in a healthy US adult population. Am J Gastroenterol. 2012 Aug;107(8):1248-55.
2. Hellström PM, Pathophysiology of the irritable bowel syndrome - Reflections of today. Best Pract Res Clin Gastroenterol. 2019 Jun - Aug;40-41:101620.
3. Diwakarla S Heterogeneity of enterochromaffin cells within the gastrointestinal tract. Neurogastroenterol Motil. 2017 Jun;29(6).
4. K.A. Gwee, S.M. Collins, N.W. Read, et al.Increased rectal mucosal expression of interleukin-1β in recently acquired post-infectious irritable bowel syndrome. Gut, 52 (2003), pp. 523-526
5. R.C. Spiller, D. Jenkins, J.P. Thornley, 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, 47 (2000), pp. 804-811
6. Matricon, J. Meleine M, Gelot A et al . Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome. Aliment. Pharmacol. Ther. 36, 1009-1031 (2012).
7. G. Barbara, V. Stanghellini, R. De Giorgio, et al.Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology, 126 (2004), pp. 693-702
8. Rodríguez LA, Ruigómez A. Increased risk of irritable bowel syndrome after bacterial gastroenteritis: cohort study. BMJ. 1999 Feb 27;318(7183):565-6.
9. Beatty JK, Post-infectious irritable bowel syndrome: mechanistic insights into chronic disturbances following enteric infection. World J Gastroenterol. 2014 Apr 14;20(14):3976-85.
10. Zanini B, Incidence of post-infectious irritable bowel syndrome and functional intestinal disorders following a water-borne viral gastroenteritis outbreak. Am J Gastroenterol. 2012 Jun;107(6):891-9.
11. Hanevik K, Development of functional gastrointestinal disorders after Giardia lamblia infection. BMC Gastroenterol. 2009 Apr 21;9:27.
12. Pokkunuri V, Role of Cytolethal Distending Toxin in Altered Stool Form and Bowel Phenotypes in a Rat Model of Post-infectious Irritable Bowel Syndrome. J Neurogastroenterol Motil. 2012 Oct;18(4):434-42.
13. Pimentel M, Morales W, Lezcano S et al Low-dose nocturnal tegaserod or erythromycin delays symptom recurrence after treatment of irritable bowel syndrome based on presumed bacterial overgrowth. Gastroenterol Hepatol (N Y). 2009 Jun;5(6):435-42.
14. Ghoshal UC et al, Frequency of small intestinal bacterial overgrowth in patients with irritable bowel syndrome and chronic non-specific diarrhea. J Neurogastroenterol Motil. 2010 Jan;16(1):40-6.
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 Jun;25(6):529-37
Steven Sandberg-Lewis, ND, DHANP, has been in clinical practice for 44 years, with a focus on functional gastroenterology. He has been a professor since 1985, teaching a variety of courses but primarily focusing on gastroenterology and GI physical medicine. In 2019, Dr. Sandberg-Lewis co-founded Hive Mind Medicine, continuing his specialization in gastroenterology with a focus on reflux, SIBO, inflammatory bowel disease and functional GI disorders. He is currently working on his latest book, Let's Be Real About Reflux: Getting to the Heart of Heartburn, written to help non-medical and medical professionals alike develop a better understanding of diseases affecting the gastrointestinal tract.
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