Acute appendicitis (AA) sends many distressed patients with severe abdominal pain to the emergency room where traditional treatment is surgical removal of the inflamed appendix. However, high costs and the risk of postoperative complications have spurred a search for different strategies to improve patient outcomes. In recent years, researchers have begun exploring the potential of probiotic usage in the management of AA.
This IPA blog delves into current evidence regarding the role of the gut microbiota in AA and the potential mechanisms by which probiotics may be beneficial in therapy.
Acute Appendicitis, in brief
The appendix is a small tube-shaped organ connected to the cecum, at the junction of the small and large intestines. Often thought to be “a redundant remnant of evolution,” the appendix is now thought to serve as a reservoir for beneficial gut bacteria and play a role in maintaining immune system health.
With a lifetime risk of 7-8%, AA is caused by several factors including luminal obstruction, bacterial overgrowth, and inflammation. When the opening of the appendix is blocked by a fecalith (stone made of feces), impaired drainage can lead to bacterial overgrowth which results in infection and inflammation of the appendix.
Severity can range from mild inflammation to severe infection and tissue damage. Complications such as appendix rupture, abscess formation, and peritonitis can arise if AA is not promptly addressed.
Antibiotics are sometimes recommended as a first approach for less severe case groups, which excludes patients with gangrenous AA, abscesses, and diffuse peritonitis. In addition, one study reported that uncomplicated AA may even resolve safely with rest and fluids, leading to comparable treatment failure rates, shorter hospital stays, and lower costs than antibiotic treatment. However, surgical intervention is often necessary.
The Gut Microbiota in Acute Appendicitis
It is well established that the gut microbiota plays a vital role in maintaining gut homeostasis and immune functions. Links between the gut microbiota and AA are being explored.
Researchers have found that individuals with AA have higher levels of opportunistic pathogens such as Clostridium and Prevotella, while beneficial bacteria like Streptococcus are decreased when compared to healthy subjects. This imbalance, known as dysbiosis, may play a role in the inflammation and infection seen in AA by altering gut barrier function and triggering an inflammatory response, leading to tissue damage and worsening of the condition.
Luminal obstruction in AA disrupts the gut microbiota balance by causing stagnation and modifying the appendix’s microenvironment, which allows pathogenic bacteria to colonize the appendix.
In addition, the appendix, rich in gut-associated lymphoid tissue (GALT), plays a crucial role in gastrointestinal immune response, suggesting that dysbiosis may potentially impact the development and progression of AA.
Appendectomy can lead to changes in gut bacteria, with one study observing an increase in short-chain fatty acid producers —unclear if beneficial or disease-promoting in this context— while another study identified specific bacteria associated with colorectal tumorigenesis and bowel inflammation.
Potential Benefits of Probiotics in Acute Appendicitis
Researchers believe that probiotics may show potential in the management of AA through several mechanisms:
- Restoring microbial balance in the gut, potentially reducing inflammation in the appendix.
- Modulating immune responses and promoting anti-inflammatory effects in the appendix, reducing severity. The balance between innate and adaptive immune responses is significantly influenced by probiotics.
- Improving gut barrier function, preventing bacterial migration from the inflamed appendix, thereby reducing inflammation, infection and complications like peritonitis.
Probiotics in Acute Appendicitis?
Studies have shown that specific single and multi-strain probiotics can improve treatment outcomes in patients with acute uncomplicated diverticulitis (AUD) and potentially have similar benefits for AA.
However, studies have yet to be done to determine whether probiotics can influence the course of AA.
Notably, probiotics may affect the risk of AA complications such as peritonitis. A study in rats found that pre-conditioning with probiotics had protective effects in induced peritonitis, thought to be due to reduced oxidative tissue damage.
Takeaway
Imbalances in the gut microbiota are associated with AA, contributing to inflammation, infection, and tissue damage, while luminal obstruction and changes in gut bacteria following appendectomy further impact the development and progression of the condition. Restoring gut microbiota balance is a possible management strategy.
Probiotics may potentially alter the gut microbiota, decrease inflammation, and create a favorable environment for the recovery of the appendix. Well-designed trials are needed to determine if probiotics may play a role.
Key references
Bi, Yuewei et al. “The Gut Microbiota and Inflammatory Factors in Pediatric Appendicitis.” Disease markers vol. 2022 1059445. 7 Jul. 2022, doi:10.1155/2022/1059445
Cai, Shuntian et al. “Appendectomy Is Associated With Alteration of Human Gut Bacterial and Fungal Communities.” Frontiers in microbiology vol. 12 724980. 16 Sep. 2021, doi:10.3389/fmicb.2021.724980
de Almeida Leite, Rodrigo Moises et al. “Nonoperative vs Operative Management of Uncomplicated Acute Appendicitis: A Systematic Review and Meta-analysis.” JAMA surgery vol. 157,9 (2022): 828-834. doi:10.1001/jamasurg.2022.2937
Di Saverio, Salomone et al. “Diagnosis and treatment of acute appendicitis: 2020 update of the WSES Jerusalem guidelines.” World journal of emergency surgery : WJES vol. 15,1 27. 15 Apr. 2020, doi:10.1186/s13017-020-00306-3
Erginel, Basak et al. “Antioxidant Effects of Probiotics in Experimentally Induced Peritonitis.” Surgical infections vol. 17,1 (2016): 114-8. doi:10.1089/sur.2015.072
Girard-Madoux, Mathilde J H et al. “The immunological functions of the Appendix: An example of redundancy?.” Seminars in immunology vol. 36 (2018): 31-44. doi:10.1016/j.smim.2018.02.005
Park, H C et al. “Randomized clinical trial of antibiotic therapy for uncomplicated appendicitis.” The British journal of surgery vol. 104,13 (2017): 1785-1790. doi:10.1002/bjs.10660
Peeters, Toon et al. “The fecal and mucosal microbiome in acute appendicitis patients: an observational study.” Future microbiology vol. 14 (2019): 111-127. doi:10.2217/fmb-2018-0203
Petruzziello, C et al. “The efficacy of a mix of three probiotic strains in reducing abdominal pain and inflammatory biomarkers in acute uncomplicated diverticulitis.” European review for medical and pharmacological sciences vol. 23,20 (2019): 9126-9133. doi:10.26355/eurrev_201910_19316
Petruzziello, Carmine et al. “Supplementation with Lactobacillus reuteri ATCC PTA 4659 in patients affected by acute uncomplicated diverticulitis: a randomized double-blind placebo controlled trial.” International journal of colorectal disease vol. 34,6 (2019): 1087-1094. doi:10.1007/s00384-019-03295-1
Petruzziello, Carmine, et al. “Probiotics, the Immune Response and Acute Appendicitis: A Review.” Vaccines, vol. 11, no. 7, June 2023, p. 1170. Crossref, https://doi.org/10.3390/vaccines11071170.
Schwiertz, Andreas et al. “Microbiota and SCFA in lean and overweight healthy subjects.” Obesity (Silver Spring, Md.) vol. 18,1 (2010): 190-5. doi:10.1038/oby.2009.167
Shi, Feiyu et al. “Altered gut microbiome composition by appendectomy contributes to colorectal cancer.” Oncogene vol. 42,7 (2023): 530-540. doi:10.1038/s41388-022-02569-3
Snyder, Matthew J et al. “Acute Appendicitis: Efficient Diagnosis and Management.” American family physician vol. 98,1 (2018): 25-33.
Zhao, Liping et al. “Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes.” Science (New York, N.Y.) vol. 359,6380 (2018): 1151-1156. doi:10.1126/science.aao5774