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SIBO: Comorbidities, SIFO, and Diagnosis

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A healthy intestinal microbiome is essential for optimal immune function and wellness. Microbial overgrowth in the small intestine has been associated with several health issues and may be caused by many factors. Small intestinal bacterial overgrowth (SIBO), specifically, is a condition that presents with a range of detrimental gastrointestinal (GI) and non-GI-related symptoms and is associated with diverse comorbid conditions. Restoring balance to gut flora through individualized interventions and tailored treatments that address lifestyle factors and nutritional needs may dramatically improve health.
In the following video, IFM educator Thomas Sult, MD, IFMCP, discusses nutritional therapies and modifiable food plans that may be appropriate for patients with SIBO.
SIBO Comorbidities
Research results have suggested links between SIBO and diseases such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), motility disorders, chronic pancreatitis, cirrhosis, and various immunodeficiency syndromes.1-3 Specific to IBS, a 2020 systematic review and meta-analysis examined 25 case-controlled studies with a total of 3,192 IBS patients and 3,320 controls and found that SIBO prevalence in patients with IBS was significantly increased.4
Additional studies have found that SIBO is more frequently present in populations with active H. pylori infection5 and celiac disease6 and may also be associated with obesity,7 rosacea,8 and nonalcoholic fatty liver disease (NAFLD) at a higher rate than controls. In a small study of obese children with SIBO, researchers found an increased risk for developing NAFLD.9 The study concluded that the relationship between intestinal dysbiosis and diet can influence the gut-liver axis.9 In addition, a 2022 meta-analysis of 18 studies (n=1,263 total participants) found that among adult patients with chronic non-alcoholic fatty liver diseases, the prevalence of SIBO was as high as 35%.10
Considering the Fungal Component
Within a healthy GI tract, bacterial and fungal organisms most heavily colonize the colon, while these microbial communities appear less in the small intestine. As with SIBO, small intestinal fungal overgrowth (SIFO) may lead to various systemic symptoms such as migraines, fatigue, depression, bloating, and more.11 Also like SIBO, intestinal dysmotility and reduced amounts of stomach acid resulting from PPI use are potential risk factors specifically for SIFO.1,12-14
While common treatments for SIBO may include antibiotics, antifungal therapy is occasionally used to address SIFO. Dietary modifications may also be beneficial for both conditions.1,15 A pilot study evaluated the effectiveness of a dietary intervention in combination with antifungals for patients with a chronic form of intestinal Candida overgrowth.15 Ten days after the diet and control groups received an antifungal treatment, both showed satisfactory antifungal and symptomatic effect with no statistically significant difference; however, at the second examination three months later, the diet intervention group showed a significantly higher percentage of patients without symptoms (85%) compared to the control group (42.5%).15
Clinical Diagnosis, Root Cause, and Treatment Considerations
SIBO can be a challenge to diagnose, and with overlapping symptoms, SIFO may also be a contributor to GI imbalance and an important factor to consider when identifying root causes and selecting optimal treatment strategies. Recent literature suggests that there is no gold standard for the diagnosis of SIBO.16 According to the American College of Gastroenterology clinical guidelines, small bowel aspirate and culture is often considered appropriate for the diagnosis of SIBO, as well as the use of breath testing for those patients with IBS; however, the guidelines acknowledge ongoing efforts for re-evaluating the criteria for a SIBO diagnosis and the optimal methods for diagnostic testing.1
For potential SIBO and SIFO diagnoses, the identification and treatment of the underlying conditions causing the microbial imbalances in the small intestine is important. Research continues to develop on the effectiveness of using probiotics and prokinetics as part of a SIBO treatment.17-20 Functional medicine approaches to improve gut health may include nutritional interventions that reduce the fermentation of carbohydrates in the gut to help address bacterial and fungal overgrowth or an elimination diet that removes trigger foods to potentially reduce inflammation and improve symptoms. Overall, IFM’s 5R framework addresses a range of GI health issues, including SIBO and SIFO, and uses specific steps—remove, replace, re-inoculate, repair, and rebalance—to help restore a natural balance to the GI system.3
To read more about augmenting SIBO interventions with nutritional therapies, please read IFM’s article Managing SIBO Through Dietary Interventions by guest authors Kara Fitzgerald, ND, IFMCP, and Lara Zakaria, RPh, MSc, CNS, CDN, IFMCP.
Join IFM at the GI Advanced Practice Module (APM) to learn clinically useful techniques such as the 5R framework for addressing all types of gastrointestinal issues. In addition to the latest research, you’ll also learn about how to develop individualized treatment protocols using lifestyle, diet, nutraceuticals, pharmaceuticals, and botanicals to help restore gut health.
Related Articles
The 5R Framework for Gut Health
Managing SIBO Through Dietary Interventions
IBS Development: Primary Causes and Triggers
References
- Pimentel M, Saad RJ, Long MD, Rao SSC. ACG clinical guideline: small intestinal bacterial overgrowth. Am J Gastroenterol. 2020;115(2):165-178. doi:14309/ajg.0000000000000501
- Lee AA, Baker JR, Wamsteker EJ, Saad R, DiMagno MJ. Small intestinal bacterial overgrowth is common in chronic pancreatitis and associates with diabetes, chronic pancreatitis severity, low zinc levels, and opiate use. Am J Gastroenterol. 2019;114(7):1163-1171. doi:14309/ajg.0000000000000200
- Patel SM, Young MC. The identification and management of small intestinal bacterial overgrowth: a functional medicine approach. Phys Med Rehabil Clin N Am. 2022;33(3):587-603. doi:1016/j.pmr.2022.04.003
- Shah A, Talley NJ, Jones M, et al. Small intestinal bacterial overgrowth in irritable bowel syndrome: a systematic review and meta-analysis of case-control studies. Am J Gastroenterol. 2020;115(2):190-201. doi:14309/ajg.0000000000000504
- Zhu D, Wang XL, Dai Y, Li SY, Wang WH. [Influence of Helicobacter pylori infection and its eradication treatment on small intestinal bacterial overgrowth]. Zhonghua Yi Xue Za Zhi. 2022;102(42):3382-3387. doi:3760/cma.j.cn112137-20220316-00551
- Shah A, Thite P, Hansen T, et al. Links between celiac disease and small intestinal bacterial overgrowth: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2022;37(10):1844-1852. doi:1111/jgh.15920
- Wijarnpreecha K, Werlang ME, Watthanasuntorn K, et al. Obesity and risk of small intestine bacterial overgrowth: a systematic review and meta-analysis. Dig Dis Sci. 2020;65(5):1414-1422. doi:1007/s10620-019-05887-x
- Wang FY, Chi CC. Rosacea, germs, and bowels: a review on gastrointestinal comorbidities and gut-skin axis of rosacea. Adv Ther. 2021;38(3):1415-1424. doi:1007/s12325-021-01624-x
- Belei O, Olariu L, Dobrescu A, Marcovici T, Marginean O. The relationship between non-alcoholic fatty liver disease and small intestinal bacterial overgrowth among overweight and obese children and adolescents. J Pediatr Endocrinol Metab. 2017;30(11):1161-1168. doi:1515/jpem-2017-0252
- Gudan A, Jamiol-Milc D, Hawrylkowicz V, Skonieczna-Zydecka K, Stachowska E. The prevalence of small intestinal bacterial overgrowth in patients with non-alcoholic liver diseases: NAFLD, NASH, fibrosis, cirrhosis-a systematic review, meta-analysis and meta-regression. Nutrients. 2022;14(24):5261. doi:3390/nu14245261
- Singh R, Mullin GE. A wasting syndrome and malnutrition caused by small intestine fungal overgrowth: case report and review of the literature. Integr Med (Encinitas). 2017;16(3):48-51.
- Su T, Lai S, Lee A, He X, Chen S. Meta-analysis: proton pump inhibitors moderately increase the risk of small intestinal bacterial overgrowth. J Gastroenterol. 2018;53(1):27-36. doi:1007/s00535-017-1371-9
- Jacobs C, Coss Adame E, Attaluri A, Valestin J, Rao SS. Dysmotility and proton pump inhibitor use are independent risk factors for small intestinal bacterial and/or fungal overgrowth. Aliment Pharmacol Ther. 2013;37(11):1103-1111. doi:1111/apt.12304
- Banaszak M, Górna I, Wozniak D, Przyslawski J, Drzymala-Czyz S. Association between gut dysbiosis and the occurrence of SIBO, LIBO, SIFO and IMO. Microorganisms. 2023;11(3):573. doi:3390/microorganisms11030573
- Otaševic S, Momcilovic S, Petrovic M, Radulovic O, Stojanovic NM, Arsic-Arsenijevic V. The dietary modification and treatment of intestinal Candida overgrowth – a pilot study. J Mycol Med. 2018;28(4):623-627. doi:1016/j.mycmed.2018.08.002
- Adike A, DiBaise JK. Small intestinal bacterial overgrowth: nutritional implications, diagnosis, and management. Gastroenterol Clin North Am. 2018;47(1):193-208. doi:1016/j.gtc.2017.09.008
- Revaiah PC, Kochhar R, Rana SV, et al. Risk of small intestinal bacterial overgrowth in patients receiving proton pump inhibitors versusproton pump inhibitors plus prokinetics. JGH Open. 2018;2(2):47-53. doi:1002/jgh3.12045
- Zhong C, Qu C, Wang B, Liang S, Zeng B. Probiotics for preventing and treating small intestinal bacterial overgrowth: a meta-analysis and systematic review of current evidence. J Clin Gastroenterol. 2017;51(4):300-311. doi:1097/MCG.0000000000000814
- Achufusi TGO, Sharma A, Zamora EA, Manocha D. Small intestinal bacterial overgrowth: comprehensive review of diagnosis, prevention, and treatment methods. Cureus. 2020;12(6):e8860. doi:7759/cureus.8860
- Nickles MA, Hasan A, Shakhbazova A, Wright S, Chambers CJ, Sivamani RK. Alternative treatment approaches to small intestinal bacterial overgrowth: a systematic review. J Altern Complement Med. 2021;27(2):108-119. doi:1089/acm.2020.0275