Vagotomy and appendix studies

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Elisabeth Svensson, Borghammer, Sørensen and colleagues (Aarhus University, Denmark, 2015 and 2016); Bojing Liu, Karin Wirdefeldt and colleagues (Stockholm, Sweden, 2017); Bryan Killinger, Viviane Labrie and colleagues (Van Andel Research Institute, with Lund and others, 2018). Funders were not recorded here.

What happened

• Vagotomy (2015): Danish registries followed patients who had surgery cutting the vagus nerve (the main nerve between gut and brainstem) in 1977–1995, against matched controls. Compared with the general population, "truncal" vagotomy (the whole trunk of the nerve cut) gave an adjusted hazard ratio of 0.85 (95% CI 0.63–1.14) overall and 0.53 (0.28–0.99) after more than 20 years. "Superselective" vagotomy (a more limited cut) gave no change (HR 1.09, 0.84–1.43). The authors said the statistical precision was limited.
• Sweden (Liu et al., Neurology 2017): 9,430 vagotomised patients (3,445 truncal, 5,978 selective) and 377,200 matched controls, 4,930 Parkinson's cases in all. Overall HR 0.96 (0.78–1.17), no association. Truncal vagotomy gave HR 0.78 (0.55–1.09), and 0.59 (0.37–0.93) when done at least 5 years before diagnosis; selective vagotomy showed nothing. The authors called the truncal result suggestive only.
• Appendix (Killinger et al., Sci Transl Med 2018): In the Swedish national patient registry (551,647 appendectomies, each matched to two controls; 2,252 Parkinson's cases), appendectomy was linked to a 19.3% lower Parkinson's risk and a 25.4% lower risk in rural residents (95% CI 14.1–35.6%), with no benefit in urban residents. In the PPMI cohort, people who had their appendix out at least 30 years before onset had onset 3.6 years later. Carriers of SNCA, LRRK2 or GBA mutations did not benefit. Appendix tissue from healthy people held clumped alpha-synuclein and its cut-down forms.
• Other cohorts disagreed. A 2016 Danish cohort of 265,758 appendectomies reported a slightly higher risk (HR 1.14, 1.03–1.27; Svensson, Mov Disord 2016). An Ontario study of 42,999 people over 35 found no difference against gallbladder surgery (HR 1.00, 0.74–1.36; Marras, Mov Disord 2016). A 2025 meta-analysis of nine studies found no association (RR 1.01, 0.90–1.12; Chin et al., Front Neurol 2025).

Why it moved us toward a cure

It put the gut-origin idea (landmark 6, landmark 18) to a test in humans, pointing at routes by which pathology might enter the brain, which could be a place to block it.

Outcome

Open. Vagotomy results are suggestive but not significant overall, appendectomy results conflict, and the signals could be confounded. Nobody should have surgery for this reason.

Sources

• Svensson et al., Ann Neurol 2015;78:522–529, DOI 10.1002/ana.24448 · Neuroscience News summary with numbers
• Liu et al., Neurology 2017;88:1996–2002, DOI 10.1212/WNL.0000000000003961 (abstract; a conference version appeared in Mov Disord 2016)
• Killinger et al., Sci Transl Med 2018;10:eaar5280, DOI 10.1126/scitranslmed.aar5280 (author manuscript read: PMC6319259) · Neuroscience News · STAT · Parkinson's Foundation review of conflicting studies
• Svensson et al., Mov Disord 2016;31:1918, DOI 10.1002/mds.26761 · Marras et al., Mov Disord 2016;31:1243, DOI 10.1002/mds.26670 · Chin et al., Front Neurol 2025, DOI 10.3389/fneur.2025.1619236 (a 2026 correction exists, DOI 10.3389/fneur.2026.1773653; contents not read)
• No retraction found for the Svensson, Liu or Killinger papers; each has only linked comments (Europe PMC, 20 Oct 2026).
• Not yet verified: the Danish truncal-vagotomy case count; the correction to the 2025 meta-analysis; the funders of these studies.