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Reazioni avverse al grano o a componenti del grano.

by luciano

La ricerca che presentiamo è un ottimo compendio delle attuali conoscenze sulla sensibilità al glutine non celiaca

“Riassunto: il grano è un alimento base importante a livello globale e fornisce un contributo significativo all’apporto giornaliero di energia, fibre e micronutrienti. Il consumo di più cereali integrali, tra cui il grano, contribuisce a ridurre il rischio del diabete, delle malattie cardiovascolari e del cancro del colon. Tuttavia, i componenti specifici del grano possono anche provocare reazioni fisiche avverse in soggetti sensibili come la celiachia (CD) e l’allergia al grano (WA). Recentemente i media hanno evidenziato una stretta correlazione tra consumo di grano ed effetti negativi sulla salute. Ciò ha motivato molti consumatori a evitare o ridurre il consumo di alimenti che contengono grano / glutine, nonostante l’assenza di CD o WA diagnosticati, sollevando domande sui meccanismi sottostanti e sui possibili effetti di nocebo. Tuttavia, studi recenti hanno dimostrato che alcuni soggetti possono soffrire di reazioni avverse in assenza di CD e WA. Questa condizione è chiamata sensibilità al glutine non celiaca (NCGS) o sensibilità al grano non celiaca (NCWS). Oltre al glutine, il grano e i prodotti derivati contengono molti altri componenti che possono scatenare sintomi, tra cui inibitori dell’α-amilasi e tripsina (ATI), lectine e carboidrati a fermentazione rapida (FODMAP). Inoltre, il modo in cui vengono elaborati gli alimenti, come l’uso di lievito o la fermentazione a lievito naturale, i tempi di fermentazione e le condizioni di cottura, possono influenzare la presenza e la bioattività di questi componenti. La presente recensione descrive sistematicamente le caratteristiche delle intolleranze legate al grano, tra cui l’eziologia, la prevalenza, i componenti responsabili, la diagnosi e le strategie per ridurre le reazioni avverse.
Extract from the study:
Non-Celiac Gluten/Wheat Sensitivity
During recent years a third group of people has been classified who experience symptoms after eating wheat products, but have been diagnosed not to suffer from either WA or CD. Mostly these individuals are self diagnosed wheat intolerant/sensitive. In these individuals, irritable bowel syndrome (IBS)-like gastrointestinal symptoms and extra-intestinal complaints occur, which improve on a gluten-free diet. This group of patients is referred to as “non-celiac gluten sensitivity” (NCGS), or the more recently, “non-celiac wheat sensitivity” (NCWS). Di Sabatino emphasizes that NCWS is not a homogeneous disease syndrome (such as CD and WA), but rather a heterogeneous syndrome (Di Sabatino & Corazza, 2012). It is probable that the underlying causes and mechanisms are not the same for all people with NCWS and that reactions may be caused by different components of wheat or grain (products) and involving different host factors. Ludvigsson et al. (2013) defined NCGS as follows: one or more of a variety of immunological, morphological, or symptomatic manifestations that are precipitated by the ingestion of gluten in individuals in whom CD has been excluded. However, despite the word “gluten” in the currently most cited definition “NCGS,” it is far from certain that the gluten is the (main) cause of the symptoms observed. The more recent term “NCWS” was adopted since it was noted that gluten (NCGS) may not be the real cause (Biesiekierski, Peters, et al., 2013; Skodje et al., 2018). For that reason, we will use the term NCWS as most appropriate in the remainder of this article.

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.

Grano monococco: perchè è così importante

by luciano

Riassunto delle principali caratteristiche del grano monococco che gli conferiscono grande potenzialità per essere utilizzato per la preparazione di prodotti da forno salati ma anche dolci per le persone che:
• sono geneticamente predisposte per la celiachia (1) (2) (3) (4) (5),
• debbono tenere sotto controllo l’indice glicemico (6),
• sensibili al glutine non celiache, reintroducono il glutine dopo la sua esclusione (7),
• hanno difficoltà con la digestione del glutine (8).
• sono sensibili alle ATI -amylase trypsina inibitors-. (9)
Da sottolineare, anche, le elevate qualità nutrizionali del grano monococco (10).

(1)- Immunogenicity of monococcum wheat in celiac patients
………..omissis. “Conclusions: Our data show that the monococcum lines Monlis and ID331 activate the CD T cell response and suggest that these lines are toxic for celiac patients. However, ID331 is likely to be less effective in inducing CD because of its inability to activate the innate immune pathways”. Immunogenicity of monococcum wheat in celiac patients. Carmen Gianfrani et altri. Am J Clin Nutr 2012;96:1339–45.

(2) ………omissis. “D’altra parte, tenuto conto che l’incidenza e la gravità della celiachia dipende dalla quantità e dalla nocività delle prolamine e che alcuni genotipi di grano monococco hanno una elevata qualità panificatoria accoppiata con assenza di citotossicità e ridotta immunogenicità, è atteso che l’uso delle farine di monococco nella dieta della popolazione generale, all’interno della quale si trova una elevata percentuale di individui predisposti geneticamente alla celiachia ma non ancora celiaci, possa contribuire a contenere la diffusione di questa forma di intolleranza alimentare. Ciò lascia pensare che il grano monococco, riportato recentemente in coltivazione in Italia dai ricercatori del Consiglio per la Ricerca e la sperimentazione in Agricoltura (CRA) di Roma e San Angelo Lodigiano, potrà svolgere un ruolo importante nella prevenzione della celiachia, sia direttamente sotto forma di pane e pasta sia indirettamente come specie modello per lo studio del ruolo dell’immunità innata nell’insorgenza della celiachia”. Le nuove frontiere delle tecnologie alimentari e la celiachia Norberto Pogna, Laura Gazza (2013).

(3)-Extensive in vitro gastrointestinal digestion markedly reduces the immune-toxicity of Triticum monococcum wheat: Implication for celiac disease
Carmen Gianfrani, Alessandra Camarca, Giuseppe Mazzarella, Luigia Di Stasio, Nicola Giardullo, Pasquale Ferranti, Gianluca Picariello, Vera Rotondi Aufiero, Stefania Picascia, Riccardo Troncone, Norberto Pogna, Salvatore Auricchio
and Gianfranco Mamone. Mol. Nutr. Food Res. 2015, 00, 1–11
Scope: The ancient diploid Triticum monococcum is of special interest as a candidate low-toxic wheat species for celiac disease patients. Here, we investigated how an in vitro gastro-intestinal digestion, affected the immune toxic properties of gliadin from diploid compared to hexaploid wheat.
Method and results: Gliadins from Triticum monococcum, and Triticum aestivum cultivars were digested using either a partial proteolysis with pepsin-chymotrypsin, or an extensive degradation that used gastrointestinal enzymes including the brush border membrane enzymes. The immune stimulatory properties of the digested samples were investigated on T-cell lines and jejunal biopsies from celiac disease patients. The T-cell response profile to the Triticum mono coccum gliadin was comparable to that obtained with Triticum aestivum gliadin after the partial pepsin-chymotrypsin digestion. In contrast, the extensive gastrointestinal hydrolysis drastically reduced the immune stimulatory properties of Triticum monococcum gliadin. MS-based analy- sis showed that several Triticum monococcum peptides, including known T-cell epitopes, were degraded during the gastrointestinal treatment, whereas many of Triticum aestivum gliadin survived the gastrointestinal digestion.
Conclusion: he pattern of Triticum monococcum gliadin proteins is sufficiently different from those of common hexaploid wheat to determine a lower toxicity in celiac disease patients following in vitro simulation of human digestion.

(4) …….omissis. “Abstract. A growing interest in developing new strategies for preventing coeliac disease has motivated efforts to identify cereals with null or reduced toxicity. In the current study, we investigate the biological effects of ID331 Triticum monococcum gliadin-derived peptides in human Caco-2 intestinal epithelial cells. Triticum aestivum gliadin derived peptides were employed as a positive control. The effects on epithelial permeability, zonulin release, viability, and cytoskeleton reorganization were investigated. Our findings confirmed that ID331 gliadin did not enhance permeability and did not induce zonulin release, cytotoxicity or cytoskeleton reorganization of Caco-2 cell monolayers. We also demonstrated that ID331 ω-gliadin and its derived peptide ω(105–123) exerted a protective action, mitigating the injury of Triticum aestivum gliadin on cell viability and cytoskeleton reorganization. These results may represent a new opportunity for the future development of innovative strategies to reduce gluten toxicity in the diet of patients with gluten intolerance”. Protective effects of ID331 Triticum monococcum gliadin on in vitro models of the intestinal epithelium. Giuseppe Jacomino et altri 2016.

ATI inibitori enzimi ailasi e tripsina. Parte II

by luciano

Anti nutritional factors in cereals, especially amylase trypsin inhibitors, affecting digestibility.
“Anti nutritional factors (ANF) play an important role in cereals to protect against infestation and animal consumption. From an agronomic point of view these pest barriers are beneficial as the required pest control measures (chemical pesticides, storage facilities) is relatively limited.
From a health point of view a large group of ANF, the ATI are of special interest as they may impact digestion in multiple ways, e.g. they:
• can reduce digestibility of food directly by inhibition of enzymes from the digestive tract (human and microbiome; Weegels 1994),
• can increase the load of allergenic peptide presented to the small intestine, thus increasing the allergenic and inflammation reactions (Junker et al. 2012; Zevallos et al 2014)
• complexation behavior may strongly interact with the small intestine epithelium that can cause inflammation by itself (Zevallos et al 2014)
• are the not yet completely understood cause of Bakers asthma (asma), the major labour related allergy (Stobnicka and Górny, 2015)
• can increase the load of non digested peptides and carbohydrates especially of non-starch polysaccharides (FODMAPS) that are a major cause of Irritable Bowel Syndrome (IBS) which affects 7% to 21% of the general population (Chey et al 2015)
• may impact the microbiome itself. This is not established in detail
From a food processing point of view ATI’s play a negative role as they inhibit enzymes that are added as processing aids for improved processing and bread quality. This reduces processing effectiveness and quality control of cereal based products. Understanding the role of ATI in cereals food processing and food digestion and mitigation of the negative effects is therefor of prime importance for food safety, security (1) and sustainability. An interesting way to mitigate the effect of ATI could be by altering its molecular structure that is stabilised by the large number of disulphide bonds (5-6 on ca. 14 kDa; Buchanan et al 1997)”. “https://www.wur.nl/en/Research-Results/Chair-groups/Agrotechnology-and-Food-Sciences/Laboratory-of-Food-Chemistry/Research/Themes/Technology-of-cereal-foods-digestibility.htm”
Note
(1). “food security” e la “food safety” possono essere considerate come le facce della stessa medaglia, due termini complementari che indicano, rispettivamente, la sicurezza economico-sociale di disporre di cibo a sufficienza per vivere (“food security”) e l’esigenza igienico-sanitaria di consumare cibo sano e acqua potabile (“food safety”).

ATI inibitori enzimi ailasi e tripsina. Parte I