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Sindrome dell’intestino irritabile: c’è un ruolo per il glutine?

by luciano

Uno studio molto importante che evidenzia la sovrapposizione dei sintomi della sindrome dell’intestino irritabile con quelli generati dalla sensibilità al glutine non celiaca dalle ATI e da Fodmaps.

“A tight link exists between dietary factors and irritable bowel syndrome (IBS), one of the most common functional syndromes, characterized by abdominal pain/discomfort, bloating and alternating bowel habits. Amongst the variety of foods potentially evoking “food sensitivity”, gluten and other wheat proteins including amylase trypsin inhibitors represent the culprits that recently have drawn the attention of the scientific community. Therefore, a newly emerging condition termed non-celiac gluten sensitivity (NCGS) or nonceliac wheat sensitivity (NCWS) is now well established in the clinical practice. Notably, patients with NCGS/NCWS have symptoms that mimic those present in IBS. The mechanisms by which gluten or other wheat proteins trigger symptoms are poorly understood and the lack of specific biomarkers hampers diagnosis of this condition. The present review aimed at providing an update to physicians and scientists regarding the following main topics: the experimental and clinical evidence on the role of gluten/wheat in IBS; how to diagnose patients with functional symptoms attributable to gluten/wheat sensitivity; the importance of double-blind placebo controlled cross-over trials as confirmatory assays of gluten/wheat sensitivity; and finally, dietary measures for gluten/wheat sensitive patients. The analysis of current evidence proposes that gluten/wheat sensitivity can indeed represent a subset of the broad spectrum of patients with a clinical presentation of IBS. (J Neurogastroenterol Motil 2016;22:547-557). Umberto Volta, Maria Ines Pinto-Sanchez et al.

Extrac from the study:
…..omissis. Experimental Evidence for a Role of Wheat Components in Irritable Bowel Syndrome. Different mechanisms have been proposed to explain how gluten may trigger gastrointestinal symptoms in the absence of celiac disease (Figure).

In vitro studies have demonstrated that digests of gliadin increase the expression of co-stimulatory molecules and the production of proinflammatory cytokines in monocytes and dendritic cells (40,57,58). Certain “toxic” (that only stimulates the innate immune response) gliadin-derived peptides such as the 31-43mer, may evoke epithelial cell dysfunction, increased IL-15 production and enterocyte apoptosis (59). Recent studies have demonstrated increased expression of TLR-2 in the intestinal mucosa of non-celiac compared to celiac patients, suggesting a role of the innate immune system in the pathogenesis of non-celiac reactions to gluten or other wheat components (49). Other studies have shown that monocytes from HLA-DQ2+ non-celiac individuals spontaneously release 2-3 fold more IL-8 than monocytes from HLA-DQ2 negative patients. This suggests that patients without celiac disease (no enteropathy and negative specific serology), but with positive HLA-DQ2 status, may represent a subpopulation reacting mildly to gluten (60). In terms of gut dysfunction, gluten sensitization in mice has been shown to induce acetylcholine release, one of the main excitatory neurotransmitters in the gut, from the myenteric plexus (57).
This correlates with increased smooth muscle contractility and a hypersecretory status with increased ion transport and water movements (57). These functional effects induced by gluten were not accompanied by mucosal atrophy, and were not observed after sensitization with non-gluten proteins. Interestingly gluten-induced gut dysfunction was particularly notable in mice transgenic for the human celiac gene HLA-DQ8 (57).
ATIs, a group of wheat proteins that confer resistance of the grain to pests, are strong inducers of innate immune responses via TLR4 and via the myeloid differentiation factor 88-dependent and -independent pathway (40). This activation occurs both in vitro and in vivo after oral ingestion of purified ATIs or gluten, while gluten-free cereals display no or minimal activities (61). The role of ATIs in IBS is not yet known, however there is clear description of a mechanism that could be involved in the generation of gut dysfunction and symptoms. These mechanisms are different from those proposed for gluten and thus it is conceivable that they could co-exist in given patients or have a synergistic effect.

Sensitivity to wheat, gluten and FODMAPs in IBS: facts or fiction?

by luciano

Roberto De Giorgio, Umberto Volta, Peter R Gibson. Published Online First 15 June 2015. Gut 2016; 65:169–178.

Riassunto
La sindrome dell’intestino irritabile (IBS) è uno dei tipi più comuni di disturbo funzionale intestinale. Una crescente attenzione è stata data al ruolo causale del cibo nell’IBS. L’ingestione di cibo fa precipitare o aggrava i sintomi, come dolore addominale e gonfiore nei pazienti con IBS attraverso diversi meccanismi ipotizzati tra cui l’attivazione immunitaria e dei mastociti, la stimolazione dei meccanorecettori e l’attivazione chemosensoriale. Il grano è considerato uno dei fattori scatenanti dell’IBS più rilevanti, anche se i componenti di questo cereale coinvolti rimangono sconosciuti. Il glutine, altre proteine, del grano, ad esempio gli inibitori dell’amilasi-tripsina e i fruttani (questi ultimi appartenenti a oligo-di-mono-saccaridi e polioli fermentabili = FODMAP), sono stati identificati come possibili fattori per la generazione / esacerbazione dei sintomi. Questa incertezza sul vero colpevole o colpevoli ha aperto uno scenario di definizioni semantiche favorite dai risultati discordanti degli studi controllati in doppio cieco controllati con placebo, che hanno generato vari termini che vanno dalla sensibilità al glutine non celiaca a quella più ampia del grano non celiaco o sensibilità alle proteine del grano o, persino, sensibilità FODMAP. Il ruolo dei FODMAP nel suscitare il quadro clinico dell’IBS va oltre, poiché questi carboidrati a catena corta si trovano in molti altri componenti dietetici, tra cui frutta e verdura. In questa recensione, abbiamo valutato la letteratura attuale al fine di scoprire se la sensibilità al glutine / grano / FODMAP rappresenti “fatti” e non “fiction” nei sintomi dell’IBS. Questa conoscenza dovrebbe promuovere la standardizzazione nelle strategie dietetiche (senza glutine / senza grano e FODMAP basso) come misure efficaci per la gestione dei sintomi IBS.

ABSTRACT
IBS is one of the most common types of functional bowel disorder. Increasing attention has been paid to the causative role of food in IBS. Food ingestion precipitates or exacerbates symptoms, such as abdominal pain and bloating in patients with IBS through different hypothesised mechanisms including immune and mast cell activation, mechanoreceptor stimulation and chemosensory activation. Wheat is regarded as one of the most relevant IBS triggers, although which component(s) of this cereal is/are involved remain(s) unknown. Gluten, other wheat proteins, for example, amylase-trypsin inhibitors, and fructans (the latter belonging to fermentable oligo-di-mono-saccharides and polyols (FODMAPs)), have been identified as possible factors for symptom generation/exacerbation. This uncertainty on the true culprit(s) opened a scenario of semantic definitions favoured by the discordant results of double-blind placebo-controlled trials, which have generated various terms ranging from non-coeliac gluten sensitivity to the broader one of non-coeliac wheat or wheat protein sensitivity or, even, FODMAP sensitivity. The role of FODMAPs in eliciting the clinical picture of IBS goes further since these short-chain carbohydrates are found in many other dietary components, including vegetables and fruits. In this review, we assessed current literature in order to unravel whether gluten/wheat/FODMAP sensitivity represent ‘facts’ and not ‘fiction’ in IBS symptoms. This knowledge is expected to promote standardisation in dietary strategies (gluten/wheat-free and low FODMAP) as effective measures for the management of IBS symptoms.

Extract from study:

WHEAT SENSITIVITY
Wheat is considered one of the foods known to evoke IBS symptoms. However, which component(s) of wheat is/are actually responsible for these clinical effects still remain(s) an unsettled issue. The two parts of wheat that are thought to have a mechanistic effect comprise proteins (primarily, but not exclusively, gluten) and carbohydrates (primarily indigestible short-chain components, FODMAPs). Two distinct views characterise the clinical debate: one line identifies wheat proteins as a precipitating/perpetuating factor leading to symptoms, while the other believes that FODMAPs are the major trigger for IBS.

The controversy over nomenclature
If gluten is a major trigger for IBS, it expands the gluten-related disorders by adding a new entity now referred to as non-coeliac gluten sensitivity (NCGS). Indeed, coeliac disease-like abnormalities were reported in a subgroup of patients with IBS many years ago. A recent expert group of researchers reached unanimous consensus attesting the existence of a syndrome triggered by gluten ingestion. This syndrome recognises a wide spectrum of symptoms and manifestations including an IBS-like phenotype, along with an extra-intestinal phenotype, that is, malaise, fatigue, headache, numbness, mental confusion (‘brain fog’), anxiety, sleep abnormalities, fibromyalgia-like symptoms and skin rash. In addition, other possible clinical features include gastroesophageal reflux disease, aphthous stomatitis, anaemia, depression, asthma and rhinitis. Symptoms or other manifestations occur shortly after gluten consumption and disappear or recur in a few hours (or days) after gluten withdrawal or challenge. A fundamental prerequisite for suspecting NCGS is to rule out all the established gluten/wheat disorders, comprising coeliac disease (CD), gluten ataxia, dermatitis herpetiformis and wheat allergy. The major issue not addressed by the consensus opinion was that gluten is only one protein contained within wheat. Other proteins, such as amylase-trypsin inhibitors (ATIs), are strong activators of innate immune responses in monocytes, macrophages and dendritic cells. Furthermore, wheat germ agglutinin, which has epithelial-damaging and immune effects at very low doses at least in vitro, might also contribute to both intestinal and extraintestinal manifestations of NCGS. Consequently, a further development of this research field led to suggestions of a broader term, non-coeliac wheat sensitivity (NCWS). The problems with this term are twofold. First, rye and barley may be inappropriately excluded. Second, the term will refer to any wheat component that might be causally related to induction of symptoms and, therefore, will also include fructans (FODMAPs). It will then have a very nonspecific connotation in IBS. A more correct term would then be non-coeliac wheat protein sensitivity (NCWPS) since this does not attribute effects to gluten without evidence of such specificity, eliminates the issue of fructan-induced symptoms and avoids the unknown contribution of rye and barley proteins to the symptoms. Both NCGS, the currently accepted term, and NCWPS will be used subsequently in this paper.