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Permeabilità intestinale, microbiota, dieta ed esercizio fisico II parte

by luciano

Una ricerca recente e approfondita sull’influenza del microbiota intestinale, della dieta e dell’esercizio fisico sulla permeabilità intestinale. Tetiana R. Dmytriv et al. 2024. DOI 10.3389/fphys.2024.1380713.

6 Exercise as a regulator of intestinal barrier integrity

Regular moderate physical exercises are one of the most common recommendations for the prevention of various pathologies, including disruption of the integrity of the intestinal barrier. This may be due to the influence of the gut microbiota. In particular, exercises have been found to increase gut bacterial diversity (Hintikka et al., 2023). However, effects of physical exercises depend on their intensity. For example, endurance athletes have a high incidence of gastrointestinal disorders and the “leaky” gut is one of the most common disorders (Ribeiro et al., 2021). It is characterized by dysfunction of the intestinal epithelial barrier and its excessive permeability. This results in penetration of harmful microorganisms, toxins or undigested food particles into the bloodstream and has a negative effect on health of the whole organism (Aleman et al., 2023).
The effect of exercise on intestinal permeability depends on its duration and intensity. For example, people who exercise frequently and intensely have the same mortality rates as people who lead a sedentary lifestyle (Van Houten et al., 2015). A 60 min bout of intensive treadmill running increased the permeability of the small intestine in runners, whereas low-intensity running had no such effect (Pals et al., 1997). Using the overtraining model with male C57BL/6 mice, it was established that exhaustive exercise exacerbated intestinal inflammation, disrupted integrity and enhanced intestine wall permeability (Hou et al., 2020). Sustained strenuous exercise in racing sled dogs increased the intestinal permeability and the frequency of gastric erosions or ulcerations (Davis et al., 2005). High-intensity interval running increased intestine wall permeability and intestinal-fatty acid binding protein (I-FABP) release in male runners (Pugh et al., 2017). I-FABP is a cytoplasmic protein expressed exclusively in the enterocytes of the small intestine and its increased concentration in the blood is used as a marker of damage to intestinal epithelial cells (Sikora et al., 2019).
Physical exercise of low/moderate intensity can often have positive effects and can be considered as a method of non-pharmacological intervention in inflammatory bowel disease (Ordille and Phadtare, 2023). For example, mice that swam for 30 min before inducing intestinal barrier dysfunction had less intestinal dysfunction compared to mice that had not swum before. This might happen due to a strengthening of antimicrobial function of the intestine as a result of the increase in expression of antimicrobial peptides (Luo et al., 2014). Obese mice that were trained on a motorized treadmill for 45 min per day 5 days a week for 12 weeks had higher expression levels of colonic ZO-1 and occludin. Moderate exercise effectively prevented the development of dysbacteriosis caused by the HFD, as well as intestinal pathology (Wang et al., 2022). Dysbacteriosis and impaired intestinal barrier integrity induced by HFD in wild type mice was prevented by exercise. Exercise on a motor-driven rodent treadmill for 5 days a week for a total of 15 weeks significantly reversed the pathological changes. Ablation of Sestrin 2 protein attenuated the protective effects of exercise, suggesting its involvement in regulation of intestinal permeability (Yu et al., 2022). Thus, it can be concluded that high-intensity exercises often have a negative effect on the integrity of the intestine, whereas low- and moderate-intensity regular exercise can have a positive effects. It may be speculated that moderate damage to the intestinal wall is a hormetic factor that may be used to train organisms to cope with severe damaging challenges. This may be used to increase the adaptive potential of organisms to prevent damaging effects of any stresses of physical and chemical nature on the integrity of the intestinal wall.

 

6.1 Exercise-induced heat stress

It is known that physical exertion causes heat stress and associated dysfunction of gut integrity. A systematic review examining the relationship between an exercise-induced increase in core body temperature and intestinal permeability demonstrated that the magnitude of exercise-induced hyperthermia correlated with increased intestinal permeability (Pires et al., 2017). An increase in body temperature is a signal to activate the expression of heat shock proteins (HSP) which constitutively function as molecular chaperones maintaining the native structure of the proteins. Their expression is mainly triggered by heat shock signals. During exercise, the level of HSP70 and HSP90 increase (Krüger et al., 2019). Expression of HSP is regulated at the level of heat shock factors (HSF) such as HSF1 that is expressed in all mammalian tissues. Normally it resides in the cytoplasm as a monomer. In response to stressful conditions, it trimerizes, translocates into the nucleus, binds to the heat shock element of target genes and activates the transcription of HSPs, including HSP70/90 (Noble and Shen, 2012).
In this way, exercises cause a homeostatic imbalance, while regular training is adaptive and decreases the degree of this imbalance. Potentially, a higher adaptive steady-state level of HSPs due to regular training could explain their positive effect on gut integrity. At that time, during acute physical exertion, HSPs probably cannot cope with that level of homeostatic imbalance caused exercise-induced heat stress.

6.2 Exercise-induced hypoxia
It is well known, that exercise causes a redistribution of blood flow between tissues. This leads to the development of hypoxia (decreased oxygen levels) in intestinal epithelial cells and activation of hypoxia-inducible factor alpha (HIF-1α) (Wu et al., 2020). Figure 3 schematically shows the influence of exercise-induced hypoxia on intestinal permeability. In normoxia (normal oxygen levels), prolyl hydroxylase hydroxylates HIF-1α at two proline residues (Pro 402 and Pro 564). This results in ubiquitination followed by subsequent proteasomal degradation of HIF-1α (Lee et al., 2004).

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7 Conclusion and perspectives
The intestinal wall is a kind of checkpoint between the external and internal environments of organisms. The wall consists of three layers: mucous, epithelial, and lamina propria. The mucous layer is inhabited by microorganisms, many of which mutually beneficially coexistence within the human body. These microorganisms modulate many if not most living processes: from the development of the immune and nervous systems at early stages of life to the induction of chronic inflammation causing neurodegeneration at aging. Despite the fact that these microorganisms have coexisted with humans for many years, under certain conditions the enteral immune system of the lamina propria can perceive them as foreign and trigger a pro- inflammatory response.
Normally, the intestinal mucosa is semipermeable. It allows selective absorption of nutrients into the bloodstream but prevents the entrance of potentially harmful microorganisms and their waste products from contact with the enteral immune system. An imbalance of the intestinal microbiota, called dysbiosis, can cause a disturbance of intestinal integrity and increase intestinal permeability. Conversely, a healthy composition of the gut microbiota can contribute to the integrity of the intestinal barrier due to increased expression and induction of the assembly of TJ proteins, activation of mucus synthesis, and antioxidant action.
Disruption of intestinal barrier function may trigger development of local and even systemic inflammation.
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In general, a vicious cycle of intestinal barrier disruption can be traced here, as excessive intestinal wall permeability provokes the development of chronic low-grade inflammation. The latter is characterized by increased production of pro-inflammatory cytokines and enhanced ROS generation, increasing intestinal barrier dysfunction.
Nutrition looks to be the simplest non-pharmacological effector of integrity and permeability of the intestinal wall. It can have both a negative effect, such as HFD inducing metabolic endotoxemia, or a positive effect, such as a diet rich in plant polyphenols or fermented dairy products, increasing the expression of TJ proteins and promoting the development of beneficial bacteria.
Exercise also can affect gut intestinal permeability. Its effects depend on duration and intensity of exercise. Acute extensive physical exertion often increases intestinal permeability which may be related to the induction of heat stress, that organisms cannot cope with at that time due to insufficient resources. On the other hand, regular low and moderate intensity exercises, that are adaptive in nature, mostly have a positive effect on the integrity of the intestine and decrease its permeability. Potentially, this may be associated with an increase in the steady-state level of HSPs and chronic activation of HIF-1α which activates the transcription of genes responsible for strengthening the intestinal barrier function.
In general, it can be concluded that proper nutrition which promotes a healthy biodiversity of the gut microbiota, combined with moderate exercise, contribute to the integrity of the intestine. Disbalanced nutrition and excessive physical activity can provoke the development of dysbacteriosis and increase intestinal permeability which can potentially lead to a pro-inflammatory response. Figure 4 schematically shows potential consequences of acute intense exercises, unhealthy diet (e.g., high-fat diet), and dysbiosis on the intestinal barrier.
Taking into account all of the above, we can outline the following future prospects:
1. Development of healthy diets to support intestinal homeostasis;
2. Use of fermented dairy products as natural pre-, pro- and postbiotics to promote a healthy gut;
3. Selection of exercises to promote intestinal integrity by frequency, intensity and duration;
4. Study of the role of intestinal HIF-2α during exercise;
5. Systemic investigation of hypoxia-induced oxidative stress as a regulator of intestinal wall permeability.
Most of these perspective avenues are directed to enhance the capability of organisms to cope with disturbing factors. That increases an adaptive capability via preadaptation/hormetic mechanisms. However, some of them may be used “to patch holes” in “leaky” intestinal wall, which is characterized by increased specific permeability of the intestinal epithelium. Intestinal barrier permeability: the infuence of gut microbiota, nutrition, and exercise. Tetiana R. Dmytriv et al. DOI 10.3389/fphys.2024.1380713. PUBLISHED 08 July 2024

Note
[1] The term “intestinal barrier” emphasizes the barrier function of the intestinal wall which protects organism against invading by bacteria or other microorganisms and potentially toxic components of microorganisms. In fact, it is a complex selective physical barrier that separates the internal environment of the body from the contents of the intestinal lumen (Bischoff et al., 2014). Figure 1 shows a schematic structure of the intestinal barrier. It consists of several layers: i) a mucous layer including inner and outer mucous sublayers inhabited by commensal microorganisms in a different extent, ii) a single layer of epithelial cells, and iii) the lamina propria, which consists of immune cells that instantly react to the invasion of foreign substances (Schoultz and Keita, 2020).
The first layer, the mucous layer, that consists mainly of a mesh polymer called mucin, is located on the side of the intestinal lumen. It is associated with community of commensal microorganisms, including bacteria, fungi, viruses, and parasites, that form the individual microbial community (Chelakkot et al., 2018). A change in the microbial composition that causes a sharp imbalance between beneficial and potentially pathogenic bacteria, including changes in its functional composition, metabolic activity or changes in their local distribution, is called dysbiosis or dysbacteriosis. The latter usually results from loss of beneficial bacteria, overgrowth of potentially pathogenic bacteria, or loss of overall bacterial diversity. This disrupts the homeostatic balance of the intestinal microbiota and has a negative impact on the host’s health. In particular, dysbacteriosis is implicated in a wide range of diseases (DeGruttola et al., 2016).
The second layer, the intestinal epithelium, consists of a single layer of several specialized epithelial cells, such as enterocytes, Goblet cells, Paneth cells, enteroendocrine cells, and microfold cells (Figure 1). Enterocytes form the basis of the intestinal epithelium and play a main role in the absorption of all consumed nutrients. Goblet cells constitute about 10% of specialized epithelial cells. They secrete mucus to protect the intestinal wall from digestive enzymes (Kim and Ho, 2010). Paneth cells contain secretory granules filled with antimicrobial peptides, that are secreted in low amounts constitutively and provide the antimicrobial properties of the intestinal mucosa. Under certain conditions, their secretion can increase dramatically (Yokoi et al., 2019). Enteroendocrine cells produce hormones regulating secretion of digestive enzymes and insulin, peristalsis of the intestine, satiety, and immune response (Bonis et al., 2021). Microfold cells transport bacteria and antigens from the epithelium to enteric immune cells that either activate or suppress the immune response (Jung et al., 2010). All these cell types collectively contribute significantly to gut homeostasis.
The third layer, lamina propria, is located under the epithelium and forms the enteric immune system that consists of a large number of leukocytes with macrophages and dendritic cells being the dominant cell types (Shemtov et al., 2023). Resident intestinal macrophages are located in close proximity to the gut microbiota, with which they often interact. They play a key role in immune sampling of luminal bacteria, contributing to the maintenance of intestinal homeostasis and regulated immune response.

[2] TJ proteins are a complex of transmembrane and cytoplasmic proteins that form tight junctions, which seal cells together to create a selective barrier, maintain cell polarity, and regulate cell processes.

Key words
tight junction, tight junction proteins, inflammation,

Permeabilità intestinale, microbiota, dieta ed esercizio fisico I parte

by luciano

Una ricerca recente e approfondita sull’influenza del microbiota intestinale, della dieta e dell’esercizio fisico sulla permeabilità intestinale. Tetiana R. Dmytriv et al. 2024. DOI 10.3389/fphys.2024.1380713.

In Evidenza
1. La parete intestinale [1] è composta da tre strati: mucosa, epiteliale e lamina propria. Lo strato mucoso è abitato da microrganismi, molti dei quali coesistono reciprocamente beneficamente all’interno del corpo umano. Questi microrganismi modulano molti se non la maggior parte dei processi viventi: dallo sviluppo del sistema immunitario e nervoso nelle prime fasi della vita all’induzione dell’infiammazione cronica che causa neurodegenerazione nell’invecchiamento. Nonostante il fatto che questi microrganismi abbiano coesistito con gli esseri umani per molti anni, in determinate condizioni il sistema immunitario enterale della lamina propria può percepirli come estranei e innescare una risposta pro-infiammatoria.

2. Normalmente, la mucosa intestinale è semipermeabile. Consente l’assorbimento selettivo dei nutrienti nel flusso sanguigno, ma impedisce l’ingresso di microrganismi potenzialmente dannosi e dei loro prodotti di scarto dal contatto con il sistema immunitario enterale. Uno squilibrio del microbiota intestinale, chiamato disbiosi, può causare un disturbo dell’integrità intestinale e aumentare la permeabilità intestinale.

3. L’eccessiva permeabilità della parete intestinale provoca lo sviluppo di un’infiammazione cronica di basso grado.

4. La nutrizione sembra essere il più semplice agente non farmacologico di integrità e permeabilità della parete intestinale. Può avere sia un effetto negativo, come l’HFD che induce l’endotossemia metabolica, sia un effetto positivo, come una dieta ricca di polifenoli vegetali o prodotti lattiero-caseari fermentati, aumentando l’espressione delle proteine TJ [2] e promuovendo lo sviluppo di batteri benefici.

5. L’esercizio fisico può anche influenzare la permeabilità intestinale. I suoi effetti dipendono dalla durata e dall’intensità dell’esercizio. Lo sforzo fisico acuto esteso spesso aumenta la permeabilità intestinale che può essere correlata all’induzione dello stress da calore, che gli organismi non possono far fronte in quel momento a causa delle risorse insufficienti. D’altra parte, gli esercizi regolari di bassa e moderata intensità, che sono di natura adattiva, hanno per lo più un effetto positivo sull’integrità dell’intestino e ne riducono la permeabilità.

La ricerca
“La parete intestinale è una barriera selettivamente permeabile tra il contenuto del lume intestinale e l’ambiente interno del corpo. I disturbi della permeabilità della parete intestinale possono potenzialmente portare a un’attivazione indesiderata del sistema immunitario enterico a causa di un contatto eccessivo con il microbiota intestinale e i suoi componenti e lo sviluppo di endotossemia, quando il livello di lipopolisaccaridi batterici aumenta nel sangue, causando infiammazione cronica a bassa intensità. In questa revisione, vengono trattati i seguenti aspetti: la struttura della barriera della parete intestinale; l’influenza del microbiota intestinale sulla permeabilità della parete intestinale attraverso la regolazione del funzionamento delle proteine a giunzione stretta, la sintesi/degradazione del muco e degli effetti antiossidanti; i meccanismi molecolari di attivazione della risposta proinfiammatoria causata dall’invasione batterica attraverso le cascate di segnalazione TIRAP/MyD88 e TRAM/TRIF indotte da TLR4; l’influenza della nutrizione sulla permeabilità intestinale e l’influenza dell’esercizio fisico con un’enfasi sullo stress da calore indotti dall’esercizio e sull’ipossia. Nel complesso, questa revisione fornisce alcune informazioni su come prevenire l’eccessiva permeabilità della barriera intestinale e i processi infiammatori associati coinvolti in molte, se non nella maggior parte delle patologie. Alcune diete e l’esercizio fisico dovrebbero essere approcci non farmacologici per mantenere l’integrità della funzione di barriera intestinale e fornire il suo funzionamento efficiente. Tuttavia, in tenera età, l’aumento della permeabilità intestinale ha un effetto ormetico e contribuisce allo sviluppo del sistema immunitario.

Introduzione

La parete intestinale è un sistema complesso composto da quattro strati: mucosa, sottomucosa, muscolo e serosa. Il termine “barriere intestinale” enfatizza la componente protettiva della parete intestinale, mentre la permeabilità intestinale è una caratteristica misurabile dello stato funzionale della barriera intestinale (Bischoff et al., 2014). La parete fornisce un assorbimento selettivo di nutrienti e altri componenti del lume intestinale. Allo stesso tempo, la barriera intestinale protegge il corpo dall’ingresso di sostanze estranee indesiderate, particelle di cibo, microrganismi e loro componenti. Negli organismi normalmente funzionanti, la permeabilità della parete intestinale è strettamente controllata, ma il suo disturbo, se non adeguatamente fissato, può portare a molte, se non la maggior parte, patologie acquisite (Gieryńska et al., 2022).

Il tratto gastrointestinale (GIT) è abitato da diversi microbi chiamati microbiota intestinale che formano una comunità molto dinamica.

Figura 1 La struttura schematica della barriera intestinale. Per i dettagli vedi il testo.

L'”Ipotesi dei vecchi amici” suggerisce che le persone si sono evolute con molti microbi che, oltre a molte funzioni fisiologiche, stimolano anche lo sviluppo del sistema immunitario e ne regolano il funzionamento (Rook, 2023). Gli antigeni microbici sono sotto costante sorveglianza da parte del sistema immunitario enterico. Le cellule T immunitarie regolatorie sono responsabili del mantenimento della tolleranza immunitaria del microbiota intestinale omeostatico (Wu e Wu, 2012). Tuttavia, l’aumento della permeabilità intestinale può promuovere la traslocazione dei batteri luminali e dei modelli molecolari associati ai microbi, in particolare i lipopolisaccaridi (LPS) dall’intestino al flusso sanguigno, innescando lo sviluppo di endotossemia e infiammazione cronica a bassa intensità (Vanuytsel et al., 2021). L’endotossemia indotta dalla dieta è definita come endotossemia metabolica. Ad esempio, Cani et al. (2007) hanno stabilito che una dieta ricca di grassi ha aumentato cronicamente le concentrazioni plasmatiche di LPS da due a tre volte.

I lipopolisaccaridi endogeni LPS vengono costantemente rilasciati a causa della morte di batteri Gram-negativi nell’intestino. Con un aumento della permeabilità della barriera intestinale, gli LPS vengono assorbiti nel flusso sanguigno portale, da dove vengono trasportati dalle lipoproteine direttamente nel fegato, formando l’asse intestino-fegato. Inoltre, sono metabolizzati dagli enzimi epatici ed escreti con la bile. Tuttavia, se la loro degradazione o l’escrezione biliare sono compromesse, l’LPS può raggiungere la circolazione sistemica, dove si lega al recettore Toll-like 4 (TLR4) su leucociti, cellule endoteliali e piastrine, causando infiammazione arteriosa. In definitiva, questo porta all’attivazione della coagulazione del sangue e alla formazione di trombi, che dimostra che l’infiammazione indotta da LPS associata all’aumento della permeabilità della parete intestinale può essere coinvolta nello sviluppo dell’aterosclerosi e delle malattie trombotiche (Violi et al., 2023). In generale, la rottura della funzione di barriera intestinale è coinvolta in molte malattie correlate e non correlate al GIT, tra cui la malattia infiammatoria intestinale, la malattia epatica associata alla disfunzione metabolica, il malassorbimento degli acidi biliari, la celia, il diabete di tipo I, l’obesità, la schizofrenia e altre (Vanuytsel et al., 2021). Potenzialmente, questo potrebbe essere superato da un intervento non farmacologico basato su dieta ed esercizi (Pražnikar et al., 2020; Ordille e Phadtare, 2023) che promuovono un ecosistema intestinale sano e alleviano i sintomi di molte patologie.

In questa recensione, descriviamo la struttura della parete intestinale e i meccanismi molecolari della risposta pro-infiammatoria causata dall’invasione batterica a causa del disturbo della permeabilità della parete intestinale, nonché le influenze del microbiota intestinale, della dieta e degli esercizi sulla permeabilità della parete intestinale. Diete specifiche ed esercizi regolari a bassa e moderata intensità sono proposti come approcci non farmacologici efficaci per mantenere l’integrità della parete intestinale e il suo funzionamento efficiente. Tuttavia, in tenera età, la perdita controllata dell’intestino può essere necessaria per innescare lo sviluppo del sistema immunitario attraverso meccanismi ormetici.

2 La struttura della barriera intestinale

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3 Permeabilità intestinale

La semipermeabilità o permeabilità selettiva è una caratteristica cruciale della parete intestinale. Limita la penetrazione degli agenti patogeni ma consente la permeabilità di nutrienti, acqua e ioni. I fattori endogeni (ad esempio, infiammazione) ed esogeni (ad esempio, componenti dietetici, sostanze tossiche o farmaci) possono aumentare la permeabilità intestinale e causare la formazione di un cosiddetto “intestino permeabile”. Quest’ultimo è caratterizzato dalla penetrazione di antigeni alimentari, commensali o batteri patogeni nel sangue, causando lo sviluppo di infiammazione (Vanuytsel et al., 2021). Alcune malattie possono anche agire come fattore dirompente della barriera intestinale. Ad esempio, diversi studi dimostrano che l’iperglicemia, una caratteristica chiave del diabete, induce la disfunzione della barriera intestinale (Thaiss et al., 2018; Dubois et al., 2023). L’esposizione prolungata al glucosio ad alti livelli aumenta la capacità di migrazione della linea cellulare del colon umano Caco-2, con il risultato che gli strati appaiono meno organizzati rispetto alle condizioni fisiologiche. In particolare, questo è associato a una diminuzione dell’espressione delle proteine della giunzione stretta (TJ), che contribuisce all’interruzione della rete strutturale ad esse associata e a un aumento della permeabilità della barriera intestinale (Dubois et al., 2023). A sua volta, questo contribuisce alla penetrazione dei batteri luminali e allo sviluppo della disbatteriosi con conseguente infiammazione. Ad esempio, Harbison et al. (2019) hanno dimostrato che i bambini con diabete di tipo I hanno disbiosi del microbiota intestinale associata ad un aumento della permeabilità intestinale. In particolare, sono stati osservati una minore diversità microbica, un numero inferiore di specie batteriche antinfiammatorie e batteri produttori di SCFA, e questi cambiamenti non sono stati spiegati dalle differenze nella dieta. Pertanto, alcune malattie, tra cui il diabete, possono anche svolgere il ruolo di disgregatori della barriera intestinale.

Mucus and epithelium are the most important components of the intestinal barrier that limit the development of inflammation. The mucous layer consists of two sublayers (Figure 1). The outerlayer is thick and loose. It is inhabited by a large number of commensal microorganisms that form colonies, and under healthy conditions pathogenic bacteria cannot outgrow them or penetrate further. In other words, homeostatic microorganisms efficiently compete with potentially pathogenic ones and prevent their excessive proliferation. The inner sublayer, on the contrary, is solid and contains only a few microbes (Usuda et al., 2021). The gut microbiota plays a major role in changing the composition of mucus, regulating its synthesis and degradation.
Epithelial cells are connected by TJ proteins (Lee et al., 2018) which regulate the absorption of water, ions, and dissolved substances. They include two functional categories of proteins: integral transmembrane proteins, located at the border of adjacent cell membranes, and adaptive peripheral membrane proteins that connect integral proteins with the actin cytoskeleton. The former includes occludin, claudins, junctional adhesion molecules, and tricellulin whereas the latter include zonula occludens-1 (ZO-1), ZO-2, and ZO-3 (Lee et al., 2018). The gut microbiota can influence the expression and localization of all of these TJ proteins.

Relationship between the Gluten-Free Diet and the Gut Microbiota

by luciano

“The human intestinal tract harbors a collection of beneficial bacteria (symbi- onts/mutualists) that perform an array of functions, including the provision of attri- butes not encoded in the human genome. This ecosystem is greatly influenced by the diet, which constitutes a major environ- mental factor driving bacterial diversity. Therefore, long-term dietary practices for treating food-related diseases might affect the composition of the resident microbiota and, thereby, its functional relationships with diverse host organs and tissues. In particular, intestinal bacteria constitute a constant challenge of antigens to their host that modulate mucosal immunity and the primary line of defence against antigens acquired orally. Celiac disease appeared as a result of dietary changes associated with the development of the agriculture and cereals cultivation. This is a chronic enteropathy caused by an aberrant immune response to cereal gluten proteins and, still the only therapy for the patients is to exclude the gluten from the diet. Although the adherence to a strict gluten-free diet (GFD) usually leads to the remission of the major clinical symptoms, nutritional deficiencies and health complications are often reported in treated patients. In addition, the microbiota of patients under a GFD is not completely restored in comparison with that of healthy subjects. In this context, we published a preliminary study to establish whether the GFD in itself could lead to modifications on the composition and immune properties of the gut microbiota. This study included 10 healthy subjects (30.3 years-old), who were following a GFD over one month by replacing the gluten-containing foods they usually ate with certified gluten-free foods (with no more than 20 parts per million of gluten). Analyses of fecal microbiota and dietary intakes, indicated that populations of generally regarded healthy bacteria decreased (Bifidobacterium, B. longum and Lactobacillus), while populations of potentially unhealthy bacteria increased parallel to reductions in the intake of polysaccharides (from 117 g to 63 g on average) after following the GFD. In particular, increases were detected in numbers of E. coli and total Enterobacteriaceae, which may include opportunistic pathogens. This evidence suggests a disruption of the delicate balance between the host and its intestinal microbiota (dysbiosis), which might favor the overgrowth of opportunistic pathogens and weaken the host defences against infection and chronic inflammation via possible alterations in mucosal immunity.

Effects of a gluten-free diet on gut microbiota and immune function in healthy adult humans.
Yolanda Sanz. Microbial Ecophysiology and Nutrition Group; Institute of Agrochemistry and Food Technology (IATA); Spanish National Research Council (CSIC); Valencia, Spain. Gut Microbes 1:3, 135-137; May/June 2010; © 2010 Landes Bioscience”.