{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:13:57Z","timestamp":1789802037926,"version":"4.0.1"},"reference-count":165,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2017,11,2]],"date-time":"2017-11-02T00:00:00Z","timestamp":1509580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Non-coeliac\/non-allergic gluten\/wheat sensitivity (NCG\/WS) is a gluten-related disorder, the pathogenesis of which remains unclear. Recently, the involvement of an increased intestinal permeability has been recognized in the onset of this clinical condition. However, mechanisms through which it takes place are still unclear. In this review, we attempt to uncover these mechanisms by providing, for the first time, an integrated vision of recent scientific literature, resulting in a new hypothesis about the pathogenic mechanisms involved in NCG\/WS. According to this, the root cause of NCG\/WS is a particular dysbiotic profile characterized by decreased butyrate-producing-Firmicutes and\/or Bifidobacteria, leading to low levels of intestinal butyrate. Beyond a critical threshold of the latter, a chain reaction of events and vicious circles occurs, involving other protagonists such as microbial lipopolysaccharide (LPS), intestinal alkaline phosphatase (IAP) and wheat \u03b1-amylase trypsin inhibitors (ATIs). NCG\/WS is likely to be a multi-factor-onset disorder, probably transient and preventable, related to quality and balance of the diet, and not to the presence of gluten in itself. If future studies confirm our proposal, this would have important implications both for the definition of the disease, as well as for the prevention and therapeutic-nutritional management of individuals with NCG\/WS.<\/jats:p>","DOI":"10.3390\/nu9111203","type":"journal-article","created":{"date-parts":[[2017,11,3]],"date-time":"2017-11-03T04:43:13Z","timestamp":1509684193000},"page":"1203","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["A New Proposal for the Pathogenic Mechanism of Non-Coeliac\/Non-Allergic Gluten\/Wheat Sensitivity: Piecing Together the Puzzle of Recent Scientific Evidence"],"prefix":"10.3390","volume":"9","author":[{"given":"Valentina","family":"Leccioli","sequence":"first","affiliation":[{"name":"Department of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia, via Ferrata 1, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Oliveri","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia, via Ferrata 1, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Romeo","sequence":"additional","affiliation":[{"name":"C.E.R.H.M. Center for Experimental Research for Human Microbiome Ludes H.E.I., Pietro Stiges Palace, Strait Street, 1436 Valletta, Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4586-9610","authenticated-orcid":false,"given":"Massimiliano","family":"Berretta","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, CRO-Aviano, National Cancer Institute, Via Franco Gallini 2, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia, via Ferrata 1, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/S0140-6736(78)92427-3","article-title":"Non-coeliac gluten sensitivity?","volume":"1","author":"Ellis","year":"1978","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/0016-5085(80)90432-1","article-title":"Gluten-sensitive diarrhea without evidence of celiac disease","volume":"79","author":"Cooper","year":"1980","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sapone, A., Bai, J.C., Ciacci, C., Dolinsek, J., Green, P.H., Hadjivassiliou, M., Kaukinen, K., Rostami, K., Sanders, D.S., and Schumann, M. (2012). Spectrum of gluten-related disorders: Consensus on new nomenclature and classification. 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