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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Microorganisms in Vertebrate Digestive Systems

Associations between History of Appendectomy and Gut Microbiota Composition: a Follow-up Cross-Sectional Study

Provisionally accepted
Matija  HadzicMatija Hadzic1*Andrija  KaracicAndrija Karacic1Paul  HammerPaul Hammer1Carsten  KrumbiegelCarsten Krumbiegel1Olga  MoskalenkoOlga Moskalenko1Daria  HadzicDaria Hadzic2
  • 1University Hospital Sveti Duh, Zagreb, Croatia
  • 2Klinicki bolnicki centar Sestre milosrdnice, Zagreb, Croatia

The final, formatted version of the article will be published soon.

ABSTRACT Appendix is thought to act as a regulatory immune organ and a gut microbiota reservoir. While appendectomy is linked to health risks, its impact on the gut microbiota remains understudied. Methods: The study was conceived as a cross-sectional retrospective follow-up study. Three comparisons were run on gut microbiota data, using self-reported metadata retrieved from an European laboratory's extensive database. Firstly, subjects with (wA) and without (noA) appendectomy at stool sampling were compared. Secondly, healthy individuals were selected based on specific criteria, comparing those with (HwA) and without (HnoA) appendectomy. Lastly, healthy (HwA) and non-healthy (nHwA) subjects with a history of appendectomy were compared. Due to the study design, the timing and cause of appendectomy were unknown. Data on confounding factors such as age, BMI and sex were analyzed as covariates. Regarding gut microbiota, alpha and beta diversity, relative abundance of phyla, genera, and metabolic pathways were compared. Results: Significant differences were found in the gut microbiota composition and functionality between 2'615 adult subjects who had and 13'103 adults who had not undergone appendectomy (wA vs. noA), but also regarding confounding factors such as age, sex and BMI. No significant differences were found in the gut microbiota between the 111 healthy adult subjects who had and the 876 adults who had not undergone appendectomy (HwA vs. HnoA) at the time of stool sampling. Significant differences were found between 111 healthy and 2'504 non-healthy subjects who had an appendectomy (HwA vs. nHwA). The gut microbiota composition of nHwA differed significantly in beta-diversity; it was less diverse (Shannon entropy) and showed decreased abundances of two genera, Eubacterium ruminantium and Lachnospiraceae FCS020. The HwA group was found to consume additional portions of vegetables and fruits and to sleep longer, but these differences were not significant. Conclusions: Our study found significant differences in the gut microbiota composition between healthy and non-healthy subjects who had an appendectomy but no difference in healthy subjects with our without appendectomy. Further studies are needed to elucidate if the differences are due to different restorative capacity over time.

Keywords: Appendectomy, Appendix, Gut Microbiota, gut bacteria, Dysbiosis

Received: 01 Sep 2025; Accepted: 03 Nov 2025.

Copyright: © 2025 Hadzic, Karacic, Hammer, Krumbiegel, Moskalenko and Hadzic. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Matija Hadzic, matija.hadzic@gmail.com

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