Maya Pimentel

Background: Approximately 462 million people live with type 2 diabetes mellitus (T2D) worldwide.1 Although, once diagnosed, T2D is a lifelong, often progressive illness that requires regular medical evaluation, it is often a preventable condition. Therefore, attention has switched from a prophylactic response to a preventive approach in T2D management. As a result, research is now evaluating other, less obvious risk factors for T2D. One field of growing interest is the relationship between appendectomies, or surgical removals of the appendix, and T2D diagnosis.

Methods:  A database search in PubMed was performed for relationships among the keywords “insulin,” “glucose tolerance,” “insulin tolerance,” “diabetes,” “insulin resistance,” “microbiome,” “appendicitis,” and “short chain fatty acids,” with exclusion criteria of studies published more than five years prior to this review.

Results: In a 2018 clinical study, after reviewing the medical history of 10,954 subjects between the years 1998 and 2013, investigators found a correlation between appendectomy procedures and later onset of T2D.2 Their findings suggested an increased risk of T2D diagnosis among patients under 30 years old who underwent an appendectomy, as compared to control. This finding poses the question: how are the appendix and diabetic glucose intolerance related? Little is known about the function of the appendix. However, growing research suggests that it plays an important role in communicating with the gut microbiome.

Following appendectomy, one significant change in the intestinal microbiome is the loss of short-chain fatty acid (SCFA) producing bacteria in the intestine.3 A cross-sectional study investigated the stool microbiome, via 16S rRNA sequencing, of patients following appendectomy procedure and compared these results to the microbial fingerprints of healthy controls. The results demonstrated a significant decrease in abundance of SCFA producers: Roseburia, Barnesiella, Butyricicoccus, Odoribacter, and Butyricimonas species.

Interestingly, another study found similar microbiome alterations with glucose tolerance. Published in 2020, the study recruited patients and divided them by glucose tolerance as well as diabetic diagnosis and performed 16S rRNA microbial sequencing of stool samples.4 After comparing microbial populations, the study found that patients with impaired glucose tolerance have significantly lower levels of SCFA, particularly butyrate, producers, similar to the appendectomy population from the previously discussed study.

Therefore, the intestinal microbiome may play an intermediate role in the association of appendectomy and T2D diagnosis. However, further research is required to validate the aforementioned hypothesis and better understand the role of the gut in host health.

Conclusion: The shared microbial dysbiosis between patients following appendix removal and patients with diabetes may, with further validation and research, provide a cohesive narrative for the association of T2D onset following appendectomy.

Works Cited:

1. Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of Type 2 Diabetes – Global Burden of Disease and Forecasted Trends. J Epidemiol Glob Health. 2020;10(1):107-111. doi:10.2991/jegh.k.191028.001
2. Lee YM, Kor CT, Zhou D, Lai HC, Chang CC, Ma WL. Impact of age at appendectomy on development of type 2 diabetes: A population-based cohort study. PLoS One. 2018;13(10):e0205502. Published 2018 Oct 16. doi:10.1371/journal.pone.0205502
3. Cai S, Fan Y, Zhang B, et al. Appendectomy Is Associated With Alteration of Human Gut Bacterial and Fungal Communities. Front Microbiol. 2021;12:724980. Published 2021 Sep 16. doi:10.3389/fmicb.2021.724980
4. Wu H, Tremaroli V, Schmidt C, et al. The Gut Microbiota in Prediabetes and Diabetes: A Population-Based Cross-Sectional Study. Cell Metab. 2020;32(3):379-390.e3. doi:10.1016/j.cmet.2020.06.011 [study]