Gut biopsies for synuclein

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

Kathleen Shannon, Ali Keshavarzian, Jeffrey Kordower and colleagues (2012); Naveed Visanji, Connie Marras, Anthony Lang, Lili-Naz Hazrati and colleagues (2015); Sun Ju Chung, Sung-Jae Myung and colleagues (2016). Funders were not read.

What happened

Since gut nerves carry Lewy pathology (landmark 257), could a routine biopsy of the gut diagnose Parkinson's early?

• Shannon 2012 (Mov Disord). Ten people with early, untreated Parkinson's (median disease duration 1.5 years) had a sigmoidoscopy (a scope of the lower colon) with biopsy. Nine samples were usable. All nine stained for synuclein in submucosal nerve fibres. None of 23 healthy controls or 23 people with inflammatory bowel disease, whose samples came from a tissue repository, showed that pattern.
• Visanji 2015 (Neurology). A stricter method, the paraffin-embedded tissue blot, which strips away normal synuclein, found aggregated synuclein in 12 of 15 early Parkinson's patients, 7 of 7 later patients, and 11 of 11 controls. Ordinary staining was positive in as many as 9 of 11 controls.
• Chung 2016 (Mov Disord). In 104 people (38 Parkinson's, 13 multiple system atrophy, 53 controls), stomach and colon biopsies showed the same synuclein staining across groups: colon 10.4% in Parkinson's versus 18.5% in controls, and stomach 31.6% versus 33.3%. Staining did not track motor or non-motor features.

Why it moved us toward a cure

It was an early attempt to see synuclein in living patients through an easy-to-reach tissue. Its failure showed that detecting synuclein is not enough; the test must detect the misfolded, disease-type form. That lesson led to the seed amplification assay (landmark 9) and to skin biopsy (landmark 134).

Outcome

Superseded. Gut biopsy is not used for diagnosis. Europe PMC links three published commentaries to the 2015 paper (not read). The 2012 sample was small (nine usable biopsies) and the 2015 and 2016 samples were small to modest.

Sources

• Shannon et al., Mov Disord 2012;27:709–715, DOI 10.1002/mds.23838, PMID 21766334
• Visanji et al., Neurology 2015;84:609–616, DOI 10.1212/WNL.0000000000001240, PMID 25589666
• Chung et al., Mov Disord 2016;31:241–249, DOI 10.1002/mds.26473, PMID 26686342
• Checked 19 Oct 2026: the Neurology volume and pages (84:609–616) match the Europe PMC record. No erratum or retraction is listed for the three papers.
• Not yet verified: full texts (abstracts only); later and larger biopsy studies; the commentaries.