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A recent and in-depth research regarding the influence of gut microbiota, diet and exercise on intestinal permeability. I Part

by luciano

A recent and in-depth research regarding the influence of gut microbiota, diet and exercise on intestinal permeability.
Tetiana R. Dmytriv et al. 2024.
For the full test: Tetiana R. Dmytriv et al. DOI 10.3389/fphys.2024.1380713. PUBLISHED 08 July 2024

Highlighted
1. The intestinal wall [21consists 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.
2. 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.
3. Excessive intestinal wall permeability provokes the development of chronic low-grade inflammation.
4. 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 [2] and promoting the development of beneficial bacteria.
5. 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.

“The intestinal wall is a selectively permeable barrier between the content of the intestinal lumen and the internal environment of the body. Disturbances of intestinal wall permeability can potentially lead to unwanted activation of the enteric immune system due to excessive contact with gut microbiota and its components, and the development of endotoxemia, when the level of bacterial lipopolysaccharides increases in the blood, causing chronic low-intensity inflammation. In this review, the following aspects are covered: the structure of the intestinal wall barrier; the influence of the gut microbiota on the permeability of the intestinal wall via the regulation of functioning of tight junction proteins, synthesis/degradation of mucus and antioxidant effects; the molecular mechanisms of activation of the pro-inflammatory response caused by bacterial invasion through the TLR4-induced TIRAP/MyD88 and TRAM/TRIF signaling cascades; the influence of nutrition on intestinal permeability, and the influence of exercise with an emphasis on exercise-induced heat stress and hypoxia. Overall, this review provides some insight into how to prevent excessive intestinal barrier permeability and the associated inflammatory processes involved in many if not most pathologies. Some diets and physical exercise are supposed to be non-pharmacological approaches to maintain the integrity of intestinal barrier function and provide its efficient operation. However, at an early age, the increased intestinal permeability has a hormetic effect and contributes to the development of the immune system.

Introduction
The intestinal wall is a complex system consisting of four layers: mucosa, submucosa, muscularis, and serosa. The term “intestinal barrier” emphasizes the protective component of the intestinal wall, whereas intestinal permeability is a measurable characteristic of the functional status of the intestinal barrier (Bischoff et al., 2014). The wall provides selective absorption of nutrients and other components of the intestinal lumen. At the same time, the intestinal barrier protects the body from the entrance of unwanted foreign substances, food particles, microorganisms, and their components. In normally functioning organisms, the permeability of the intestinal wall is tightly controlled but its disturbance, if not adequately fixed, can lead to many, if not most, acquired pathologies (Gieryńska et al., 2022).
The gastrointestinal tract (GIT) is inhabited by diverse microbes called gut microbiota forming very dynamic community.

 

Figure 1 The schematic structure of the intestinal barrier. For details see the text.

The “Old Friends Hypothesis” suggests that people coevolved with many microbes that, in addition to many physiological functions, also stimulate the development of the immune system and regulate its operation (Rook, 2023). Microbial antigens are under constant surveillance by the enteric immune system. Regulatory immune T cells are responsible for maintaining immune tolerance of homeostatic gut microbiota (Wu and Wu, 2012). However, increased intestinal permeability can promote translocation of luminal bacteria and microbial-associated molecular patterns, in particular, lipopolysaccharides (LPS) from the gut into bloodstream, triggering the development of endotoxemia and chronic low- intensity inflammation (Vanuytsel et al., 2021). Diet-induced endotoxemia is defined as metabolic endotoxemia. For example, Cani et al. (2007) established that a high-fat diet chronically increased plasma LPS concentrations two-to threefold.
Endogenous lipopolysaccharides LPS are constantly released as a result of the death of Gram-negative bacteria in the gut. At increased intestinal barrier permeability, LPS are absorbed into the portal bloodstream, from where they are transported by lipoproteins directly into the liver, forming the gut-liver axis. Further, they are metabolized by liver enzymes and excreted with bile. However, if their degradation or biliary excretion are impaired, LPS can reach the systemic circulation, where they bind to Toll-like receptor 4 (TLR4) on leukocytes, endothelial cells, and platelets, causing arterial inflammation. Ultimately, this leads to activation of blood coagulation and thrombus formation, which demonstrates that LPS-induced inflammation associated with increased intestinal wall permeability may be involved in the development of atherosclerosis and thrombotic diseases (Violi et al., 2023). In general, disruption of intestinal barrier function is involved in many GIT-related and unrelated diseases, including inflammatory bowel disease, metabolic dysfunction-associated liver disease, bile acid malabsorption, celiac disease, type I diabetes, obesity, schizophrenia, and others (Vanuytsel et al., 2021). Potentially, this could be overcome by a non-pharmacological intervention based on diet and exercises (Pražnikar et al., 2020; Ordille and Phadtare, 2023) which promote a healthy gut ecosystem and alleviate the symptoms of many pathologies.
In this review, we describe the structure of the intestinal wall and molecular mechanisms of the pro-inflammatory response caused by bacterial invasion due to the disturbance of the intestinal wall permeability, as well as influences of the gut microbiota, diet, and exercises on the permeability of the intestinal wall. Specific diets and regular low- and moderate-intensity exercises are proposed as effective non-pharmacological approaches to maintain integrity of intestinal wall and its efficient operation. However, at an early age, controlled leakage of the intestine may be necessary to trigger the development of immune system via hormetic mechanisms.

2 The structure of the intestinal barrier
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3 Intestinal permeability
Semi-permeability or selective permeability is a crucial feature of the intestinal wall. It limits penetration of pathogens but allows the permeability of nutrients, water, and ions. Endogenous (e.g., inflammation) and exogenous (e.g., diet components, toxicants, or drugs) factors can increase intestinal permeability and cause the formation of a so-called “leaky gut.” The latter is characterized by the penetration of food antigens, commensals, or pathogenic bacteria into the blood, causing the development of inflammation (Vanuytsel et al., 2021). Some diseases can also act as a disruptor factor of the intestinal barrier. For example, several studies show that hyperglycemia, a key feature of diabetes, induces intestinal barrier dysfunction (Thaiss et al., 2018; Dubois et al., 2023). Prolonged exposure to glucose at high levels increases migration capacity of human colonic cell line Caco-2, resulting in layers appearing less organized than under physiological conditions. In particular, this is associated with decreased expression of tight junction (TJ) proteins, which contributes to the disruption of the structural network associated with them and an increase in the permeability of the intestinal barrier (Dubois et al., 2023). In turn, this contributes to the penetration of luminal bacteria, and the development of dysbacteriosis resulting in inflammation. For example, Harbison et al. (2019) showed that children with type I diabetes have gut microbiota dysbiosis associated with increased intestinal permeability. In particular, lower microbial diversity, lower numbers of anti-inflammatory bacterial species, and SCFA- producing bacteria were observed, and these changes were not explained by differences in diet. Thus, some diseases, including diabetes, can also play the role of disruptors of the intestinal barrier.
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.

3.1 Influence of the gut microbiota on tight junction proteins
TJ proteins regulate the rate of paracellular transport including the transport of consumed nutrients via the path between neighboring epithelial cells. In electron micrographs TJ proteins look like points of fusion of the membranes of neighboring cells where there is no intercellular space in these places (Gonzalez- Mariscal et al., 2003). They play the role of sensors of environmental conditions that dynamically regulate the paracellular transport of solutes (Ulluwishewa et al., 2011). Dysregulation of TJ proteins can lead to excessive permeability of the intestinal barrier.
Bacteria can change the expression and distribution of TJ proteins and thus affect intestinal permeability. For example, some pathogenic strains of Escherichia coli, including E. coli O157:H7 strain which causes bloody diarrhea, produce toxins such as Shiga toxins (STx). The latter suppress protein biosynthesis and contribute to the development of hemolytic uremic syndrome, which is a life-threatening complication. Pradhan et al. (2020) found that STx2a decreases the expression of TJ proteins such as ZO-2, occludin, and claudin-1 (Pradhan et al., 2020). However, this strain requires the presence of non-pathogenic E. coli, which enhances the expression of Stx2a. In this way, non- pathogenic E. coli decreases the expression of TJ proteins, increasing the production of the STx2a toxin by E. coli O157:H7 strain (Xiaoli et al., 2018). This indicates that, under certain conditions, even non- pathogenic microbiota can have a negative impact on intestinal wall permeability. Contrarily, the use of probiotics (living microorganisms that are beneficial to the host organism when administered in adequate amounts) may contribute to the integrity of the intestinal barrier (Ulluwishewa et al., 2011; Gou et al., 2022). In particular, Lactobacillus and Bifidobacterium species are the most commonly used probiotics. For example, Lactobacillus reuteri increases the expression of TJ proteins and thus supports the integrity of the intestinal wall (Gou et al., 2022). Oral administration of L. reuteri I5007 significantly increased the levels of claudin-1, occludin, and ZO-1 in newborn piglets. An in vitro study showed that pretreatment of intestinal porcine epithelial cell line J2 with this bacterial strain suppressed a LPS-induced decrease in TJ protein expression (Yang et al., 2015). Administration of L. plantarum into the duodenum of healthy people increased the level of ZO-1 and occludin. However, L. plantarum did not significantly affect expression of occludin in vitro human epithelial model but induced translocation of ZO-1 into the TJ region which forms a paracellular seal between epithelial cells (Karczewski et al., 2010; Caminero et al., 2023). Bifidobacterium infantis and L. acidophilus prevented dysregulation of occludin and claudin-1 levels in colon carcinoma cell line (Caco-2) stimulated by IL-1β treatment. These strains normalized their expression and contributed to the integrity of the intestinal barrier (Guo et al., 2017). For convenience, we have summarized some available information regarding the influence of different probiotic bacterial strains on TJ proteins in Table 1. In general, probiotic bacteria can both increase and decrease TJ proteins. However, in most cases, this does not cause excessive intestinal permeability, but on the contrary, normalizes it and contributes to its integrity.
Antibiotics used to treat bacterial infections may adversely affect the gut microbiota. They cause an imbalance between specific groups of bacteria and trigger the development of dysbacteriosis (Tulstrup et al., 2015). Dysbacteriosis, in turn, contributes to intestinal permeability. An increase in the population of pathogenic bacteria at dysbacteriosis which probably produce higher levels of LPS, can damage epithelial cells of the intestinal barrier and contribute to increased intestinal permeability. For example, it was shown that changes in the microbial composition correlated with an increase in intestinal permeability in alcohol- dependent subjects (Leclercq et al., 2014).
In addition, the gut microbiota is a significant source of digestive proteases used to break down host proteins for their own needs. However, excessive activity of microbial proteases can disrupt the epithelial components of the intestinal barrier due to cleavage of TJ proteins. In turn, changes in TJ proteins lead to an increase in the paracellular permeability of the epithelial barrier (Caminero et al., 2023).

3.2 The role of gut microbiota in biosynthesis and degradation of mucous layer components

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3.3 Antioxidant effects of intestinal microorganisms

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4 Molecular mechanisms of the activation of pro-inflammatory response caused by bacterial invasion

Dysbacteriosis of the gut microbiota can lead to disruption of intestinal barrier function and immune homeostasis. Increased intestinal permeability facilitates the translocation of microbes, their components, and microbial products into the blood stream and their recognition by the host immune cells (Longo et al., 2020). The gut microbiota is the main reservoir of pro-inflammatory endotoxins inside the body. In particular, LPS, the main component of the outer membrane of Gram-negative bacteria, can cause so-called endotoxemia. The latter develops when the level of LPS in the blood increases and this leads to the activation of a pro-inflammatory immune response triggering systemic low-grade inflammation (André et al., 2019). A diet-induced increase in LPS concentration in the blood is called metabolic endotoxemia. The level of LPS in the blood serum of mice that consumed high-fat diet (HFD) for 4 weeks is similar to its level in metabolic endotoxemia (Mohammad and Thiemermann, 2021). This clearly shows how nutrition can affect intestinal permeability and immune response.
The dynamic interaction between the gut microbiota and the intestinal immune system plays a key role in maintaining intestinal homeostasis. Host cells contain pattern recognition receptors (PRRs) which recognize bacterial pathogen-associated molecular patterns (PAMPs). The latter are highly conserved bacterial motifs, possessed in LPS, oligodeoxynucleotides, peptidoglycans, and others that can trigger host immune response (Asiamah et al., 2019).
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4.1 Early/late activation of inflammation by TIRAP/MyD88 and TRAM/TRIF
signaling cascades

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Some dairy products, such as kefir, have long been studied as regulators of intestinal integrity. For example, consumption of kefir for 21 days by healthy people with two washout periods in-between decreased the serum level of zonulin (Novak et al., 2020) Kefir diet also normalized zonulin level in overweight people (Pražnikar et al., 2020). Zonulin is a protein that increases the permeability of the intestinal barrier and is often involved in the development of autoimmune diseases, including type I diabetes. Zonulin causes TJ disassembly and thus violates the intestinal barrier (Fasano, 2011). Therefore, zonulin is considered a serum marker of the integrity of the intestinal wall.
Polyphenolic compounds (secondary plant metabolites with a long list of beneficial properties for humans) are other food components that improve intestinal integrity. Flavonoids are among most abundant representatives of this group. They are found mostly in fruits, vegetables, grains, tea, and wine (Kasprzak-Drozd et al., 2021). For example, the flavonoid quercetin increased intestinal integrity, as studied in Caco-2 cells (Suzuki and Hara, 2009). This effect was associated with the assembly of ZO-2, occludin and claudin-1, as well as increased expression of claudin-4 and transepithelial electrical resistance. The electrical resistance of epithelial cells is a reliable indicator of the integrity and permeability of the cell monolayer and TJ (Srinivasan et al., 2015). The consumption of quercetin in food increased the mRNA levels of occludin and ZO-1 in pigs that was accompanied by a decrease in serum endotoxin (Zou et al., 2016), a marker of metabolic endotoxemia frequently associated with increased intestinal permeability. The flavonoid kaempferol may have similar effects. In a study on Caco-2 cells during the first 6 hours after kaempferol administration, transepithelial electrical resistance increased significantly and this correlated with the assembly of occludin and claudin-3 (Suzuki et al., 2011).
A meta-analysis performed to study the effects of oral administration of phenolic compounds on the integrity of the intestinal barrier in animals confirmed their beneficial effects. In particular, the improvement of intestinal wall integrity occurs due to the three main mechanisms: i) increased expression of TJ proteins, ii) decreased levels of pro-inflammatory molecules, and iii) increased intracellular antioxidant potential (Sandoval-Ramírez et al., 2021).

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Thus, nutrition can affect the integrity of the intestine and this is often associated with various pathological conditions. The effect mainly occurs at the level of modulation of gut microbiota composition and regulation of TJ protein operation. In this regard, healthy nutrition can be considered as a promising way to attenuate various pathologies.

A recent and in-depth research regarding the influence of gut microbiota, diet and exercise on intestinal permeability II part

The Gut Microbiota and Inflammation: An Overview

by luciano

Highlighted

“Role of the Gut Microbiota in Immunity and Inflammation
Microbes possess a variety of functions that influence their ability to grow and colonise, whilst bringing about downstream effects for the host that may be beneficial or otherwise [61]. Humans are not capable of digesting some components of dietary fibre due to the lack of the required enzymes to break down and harness the energy of these carbohydrates [62]. Certain species of microbes produce specific enzymes that enable fermentation of nutrients into absorbable forms, including that of indigestible carbohydrates into short-chain fatty acids (SCFAs) [62,63]. These SCFAs may have anti-inflammatory and immunomodulatory effects [63]. SCFAs are only a small part of the bigger picture as, in addition to enzymes and other metabolites produced, components of the bacteria themselves, including lipopolysaccharides, cell capsule carbohydrates and other endotoxins, may also be released and result in secondary effects to the host. These effects include maintenance of gut epithelium (and thereby integrity of the gut wall), production of vitamins, and interactions with several key immune system signalling molecules and cells, activating and inhibiting specific responses [1]. In addition to nutrient metabolism, gut microorganisms affect aspects of pharmacokinetics as they carry out drug metabolism [64]. They provide a natural defence against pathogenic species through competition and maintenance of the mucosa. It is through their contact with the immune system that the microorganisms occupying the gut can elicit or prevent inflammation. They may be associated with anti-inflammatory mechanisms, stimulating regulatory cells of the immune system to inhibit inflammation [65]. On the other hand, as bacteria regulate the permeability of the intestines, certain species can promote a “leaky gut”, where metabolites associated with the microbes leave the gut and enter the bloodstream. In response, the body produces cytokines and other mediators, effectively launching an inflammatory response [66]. Similarly, cells within the epithelial tissue of the gut deliver bacterial metabolites to immune cells, promoting inflammation on both a local and systemic scale. The persistence of this condition may lead to subacute or chronic inflammation, which may subsequently drive the development of diseases such as inflammatory bowel disease, diabetes or cardiovascular disease [65].”

Wheat Bran overview part II

by luciano

Impact of wheat bran physical properties and chemical composition on whole grain flour mixing and baking properties. Sviatoslav Navrotskyi, Gang Guo et al. https://doi.org/10.1016/j.jcs.2019.102790

Abstract
Wheat bran can have diverse chemical composition and physical properties. The objective of this study was to determine the associations among physical and chemical properties of bran and the mixing and baking properties of whole wheat flour. Eighty samples of bran were milled into fine (463 μm) and coarse (783 μm) particle size groups and analyzed for water retention capacity, protein, ash, lipoxygenase activity, antioxidant activity, sulfhydryl groups, and extractable phenolics. Brans were mixed with a single refined flour to make reconstituted whole wheat flour and analyzed for mixing and baking quality. Fine particle size samples had larger bread loaf volume, and softer bread texture compared to the coarse samples. Bran protein and extractable phenolics showed positive correlations with dough strength (p < 0.01) and development time (p < 0.01), respectively. Bran ash was positively correlated with dough strength (p = 0.004). Water retention capacity (WRC) of bran was significantly correlated with dough development time (p = 0.002), bread volume (p = 0.002) and initial hardness (p = 0.007) and firmness (p = 0.028). Overall, this study suggested a strong relationship between bran protein, ash, extractable phenolics, and water retention capacity and whole wheat flour functional properties.

Introduction
Whole grain foods are well known for their nutritional benefits (Hemdane et al., 2016a, Hemdane et al., 2016b). Epidemiological studies have shown that whole grain foods decrease the risk of type 2 diabetes, obesity, and heart disease (Cho et al., 2013) These benefits are likely derived from the combination of vitamins, minerals, antioxidants, and dietary fibers that are present in wheat bran.
Despite the health benefits of whole grains, wheat bran (i.e., non-flour components) tends to decrease dough strength and mixing and fermentation tolerance and reduce bread volume and crumb softness (Gajula, 2007). The negative properties of wheat bran are the result of interactions between flour components (mainly gluten) and either chemical components of the bran, such as dietary fibers, phenolics, antioxidants, low molecular weight sulfhydryl compounds, and enzymes (Khalid et al., 2017, Noort et al., 2010), or physical properties of the bran, such as water retention capacity (WRC) and bran particle size (Jacobs et al., 2015).

One of the main contributors to the poor functionality of the whole grain flour are dietary fibers. Dietary fibers generally result in reduced bread volume and poor texture (Mishra, 2016). The negative effects of dietary fibers on bread volume and texture can be by explained in many instances by the competition for water between these carbohydrate polymers and gluten proteins, which causes dough weakening (Rosell et al., 2010).

Antioxidants can interact with gluten proteins by reducing disulfide-sulfhydryl interchange reactions, thus impacting gluten protein aggregation (Huang et al., 2018).
Antioxidant properties of wheat brans are mainly determined by their free, bound and conjugated phenolic content. The role of these phenolic compounds in gluten network formation can be explained by their ability to react with gluten protein sulfhydryl groups or increase the rate of protein sulfhydryl-disulfide interchanges (Han and Koh, 2011).
For instance, the addition of phenolic acids to bread decreases dough mixing time, tolerance, and elasticity and decreases bread volume (Han and Koh, 2011).
Free sulfhydryl compounds, which are concentrated in the bran and germ of the wheat kernel, contribute to considerable dough softening (Noctor et al., 2012).
Among all low molecular weight sulfhydryl compounds present in the wheat kernel, glutathione is the most studied. Glutathione has a negative effect on gluten network development by forming disulfide bonds with cysteine residues of gluten proteins and thus terminating gluten macropolymer formation (Noctor et al., 2012).

Tra tutti i composti sulfidrilici a basso peso molecolare presenti nel chicco di grano, il glutatione è il più studiato. Il glutatione ha un effetto negativo sullo sviluppo della rete del glutine formando legami disolfuro con i residui di cisteina delle protein ​del glutine e interrompendo così la formazione dei macropolimeri del glutine (Noctor et al., 2012).

Finally, bran-associated enzymes have variable effects on bread quality. For example, lipoxygenase (LOX) produces active peroxides that can oxidize glutenin thiol groups and promote gluten macropolymer formation (Bahal et al., 2013). However, LOX can impact the flavor of products by catalyzing hydroperoxidation of polyunsaturated fatty acids, which leads to the formation of grassy or beany off-flavors (Hemdane et al., 2016a, Hemdane et al., 2016b).

Bran composition varies among different wheat lines and growing environments (Hossain et al., 2013, Cai et al., 2014). Additionally, due to the different distribution of chemical components among the bran layers (Hemdane et al., 2016a, Hemdane et al., 2016b), milling performance can significantly influence the chemical composition of bran.

Furthermore, bran particle size also has a significant impact on bread quality (Xu et al., 2018), although contradicting results have been reported. de Kock et al. (1999) reported higher loaf volumes by utilizing coarse bran (1800 μm) compared to fine bran (750 μm), and Noort et al. (2010) showed a linear increase in loaf volume with an increase in bran particle size from 70 to 1000 μm.

Inoltre, anche la dimensione delle particelle di crusca ha un impatto significativo sulla qualità del pane (Xu et al., 2018), sebbene siano stati riportati risultati contraddittori. de Kock et al. (1999) hanno riportato volumi di pane più elevati utilizzando crusca grossolana (1800μm) rispetto alla crusca fine (750μm), e Noort et al. (2010) hanno mostrato un aumento lineare del volume del pane con un aumento della dimensione delle particelle di crusca da 70 a 1000μm

However, Zhang and Moore (1999) reported the largest loaf volumes for samples containing medium particle size bran (415 μm) compared with coarse (609 μm) and fine (278 μm). The conflicting reports could be explained by differences in chemical composition among brans, or by differences in milling and baking techniques used.

The present study was designed to identify the role of chemical and physical properties of wheat bran in the mixing and breadmaking quality of whole wheat flour. Chemical components that were most likely to influence flour functionality were selected, taking into consideration the number of samples analyzed. Ultimately, bran particle size, protein, ash, free sulfhydryl groups, extractable phenolics, antioxidant activity, LOX activity, and WRC were evaluated, with dietary fiber evaluated on a subset of samples (due to the laborious nature of dietary fiber analysis). Because we desired to examine the functionality of bran independently of endosperm properties, bran samples were combined with a single based flour to make reconstituted whole grain flours for mixing and baking tests.
Specifically, the coarse particle size brans had significantly higher WRC and lower antioxidant activity. Other chemical components were not significantly impacted by particle size of the bran.
The differences in WRC among bran particle size fractions may be explained by the enhanced ability of coarse particles to trap weakly bound water compared with fine particles

Wheat Bran: overwiew part I

by luciano

Research regarding the composition and characteristics of wheat bran

1 – Wheat Bran
“Wheat bran includes the outer layers of the grain including the pericarp, head and aleurone layer (millers definition). Bran is an important by-product of milling wheat, when white flour is produced (see Section 3.3). The chemical composition (Table 5.4) is characterized by the high content (ò45%) of non-starch polysaccharides (food fibre) consisting mainly of arabinoxylans (ò60%) and cellulose (ò30%). Further characteristics are the relatively high content of minerals (potassium and phosphorus), unsaturated fatty acids (linoleic and oleic acids) and vitamins (nicotinamide, pantothenic acid and a-tocopherol). A disadvantage of bran is that the high lipid content can cause rancidity. Therefore bran is often heat treated (stabilized) to prevent enzymatic oxidation of fat.

Table 5.4. Chemical composition of wheat bran [18]

Due to the valuable nutritional composition, wheat bran has been widely used as component for animal feed (see Section 4.6), in particular for livestock like horses, cattle, goats, pigs, and rabbits. In recent years, wheat bran has increasingly been in the limelight as dietary supplement for human nutrition. Many studies have shown that the consumption of wheat bran, containing a unique mixture of valuable bioactive components, improves bowel functions and reduces the risk of colon cancer, type 2 diabetes, and cardiovascular diseases (see Section 6.4). Due to valuable antioxidants, its intake can prevent the onset of various oxidative stress-related diseases. Wheat bran is therefore frequently used as food additive, for example for bread, other baked products, and breakfast cereals [19]. It has been introduced into various further market segments including functional foods, nutraceuticals, and pharmaceuticals. Increased consumer awareness of the health benefits of bran induced great demand and food-grade bran can now easily be purchased in drugstores, health food shops, and supermarkets. Taken together, wheat bran is no longer a useless waste product but can be used in many areas of applications. Wheat-based raw materials Herbert Wieser, Katharina A. Scherf, in Wheat – An Exceptional Crop, 2020.”

2 – Wheat Bran
“Wheat bran is a by-product of wheat grain milling and grinding. The physiological effects of wheat bran can be split into the following: nutritional effects from its constituent nutrients; mechanical effects in the gastrointestinal tract due to its fiber content; and antioxidant effects arising from its phytochemical constituents. Wheat bran has higher antioxidant activity than other milled fractions, and contains various components such as phytic acid, polyphenols (including lignans and phenolic acids), vitamins, and minerals. These components of wheat bran possess health benefits for humans, including preventative effects against cancer and type 2 diabetes. Various studies have reported that these compounds exhibit significant antioxidant capabilities, including scavenging free radicals, chelating metal ions, and activating antioxidant enzymes, suggesting antioxidant properties of wheat bran. This chapter includes an overview of stress and oxidative stress and a discussion of the antioxidant properties of wheat bran. Chapter 15 – Antioxidant Properties of Wheat Bran against Oxidative Stress. Masashi Higuchi. https://doi.org/10.1016/B978-0-12-401716-0.00015-5.”

4 – Wheat bran
“Antioxidants (in bran) can interact with gluten proteins by reducing disulfide-sulfhydryl interchange reactions, thus impacting gluten protein aggregation. (Huang et al., 2018).”

5 – Wheat bran
“Bran is the most prominent co-product of the wheat milling process. In this process, the largest part of the endosperm tissue, i.e. the flour, is separated from the germ and bran after consecutive grinding, sieving and purification steps (Hemdane et al., 2016). From a botanical point of view, bran is a collection of multiple histological layers (i.e. outer and inner pericarp, seed coat and nucellar epidermis) of the outer part of the wheat kernel. However, wheat bran obtained as a milling fraction (referred as miller’s bran) also includes the aleurone layer and some residual endosperm tissue attached to it. Its yield varies between 13 to 19% of the total kernel weight (Deroover et al., 2020; Hemdane et al., 2016; Onipe et al., 2015). In this review, the term wheat bran refers to the miller’s bran.
Wheat bran mainly consists of arabinoxylan (17-33%), cellulose (9-14%) and fl-D-glucan (1-3%), but also starch (6-30%), proteins (14-26%), lipids (3-4%), lignin (3-10%), minerals (5-7%), phytic acid (4.5-5.5%), fructans (3-4%), and phenolic compounds (0.4-0.8%) (Hemdane et al., 2016). The pericarp is the main source of the kernel’s dietary fiber (mainly cross-linked arabinoxylans, cellulose and lignin). The aleurone layer is rich in arabinoxylan but also in lignan, phytic acid, minerals and vitamins (Deroover et al., 2020; Onipe et al., 2015).
Wheat minerals which are important for human health include iron, zinc, calcium, manganese, magnesium and copper. They are mainly located in the aleurone cells. Magnesium plays an important role in blood glucose homeostasis and insulin sensitivity (Veronese et al., 2016). However, minerals in wheat have low bioavailability because they are chelated by mainly phytic acid and/or because they are physically entrapped into rigid aleurone cells (Lemmens et al., 2019).
Bran is the main source of the phenolic compounds in wheat. Ferulic acid is the most abundant C6 – C3 phenolic acid. It is esterified to some of the arabinoses in the arabinoxylan chains. Arabinoxylan chains are cross-linked by formation of ferulic acid dimers and higher oligomers which are esterified to the arabinoxylan chains. Bran also contains the C6 – C3 phenolic acids sinapic and p-coumaric acid and the C6 – C1 phenolic acids p-hydroxybenzoic, vanillic, syringic, and gallic acid (Laddomada et al., 2015). Components of wheat and their modifications for modulating starch digestion: Evidence from in vitro and in vivo studies. Konstantinos Korompokis, Jan A. Delcour, in Journal of Cereal Science, 2023.”

5 – Wheat bran

“Wheat bran is a rich source of dietary fiber and other healthy components, which are biologically active, such as alkylresorcinol, ferulic acid, fl-glucan, arabinoxylan, lignans, and sterols (Pr¸ckler et al., 2014). Besides nonstarch carbohydrates (arabinoxylan, cellulose, fructan, and mixed-linkage fl-glucan), wheat bran contains starch, protein, lipids, and significant quantities of B vitamins and minerals (Hemdane et al., 2016a). The composition of wheat bran is presented in Table10.1 (USDA, 2015).”

6 – Wheat bran

“Wheat bran is a by-product of flour milling and frequently used as ingredient in diets for pigs (Huang et al., 1999; Hassan et al., 2008). It is composed of the pericarp and the outermost tissues of the seed, including the aleurone layer with variable amounts of remaining starchy endosperm (Jondreville et al., 2000; Hassan et al., 2008). Wheat bran constitutes almost 10% of the total weight of wheat milled for flour (Hassan et al., 2008). It is characterized by a high level of insoluble lignified fiber which is known to be extremely resistant to degradation in the gastrointestinal tract (Noblet and Le Goff, 2001). Molist et al. (2011) concluded that incorporation of WB in diets for piglets improved gut health by beneficially modulating the activity and composition of the intestinal microbiota.”

7 – Wheat bran
“Wheat bran is a by-product of the milling process of wheat. It usually contains 14-19% of total grain weight. As a rich source of dietary fibre, wheat bran contains 46% of non-starch polysaccharides, including arabinoxylan (70%), cellulose (24%) and beta-glucan (6%), and it also contains minor amounts of glucoglucomannan and arabinogalactan (Carre and Brillouet, 1986; Bertrand et al., 1981).
Depending on composition and particle size, wheat bran fractions may have negative effects on product quality, such as textural properties and loaf volume for bread. Reducing the particle size of wheat bran can influence product quality by increasing interaction surface and releasing reactive intracellular components (Noort et al., 2010).”

Gluten free products and human health

by luciano

Highlighted:
1 – In gluten-free products it was founded nutrient deficiencies for essential minerals such as iron, zinc magnesium and calcium, and on another hand high content of saturated lipids were detected Industrial gluten-free products in many cases contain palm and palm kernel oil
2 – Despite improvements in the formulation of GFPs in recent years, their macronutrient profile suggested they contained marked differences and cannot be considered nutritionally equivalent when compared with their gluten-containing counterparts
3 – Good fats include monounsaturated and polyunsaturated fats. Bad ones include industrial-made trans fats. Saturated fats fall somewhere in the middle
4 – In 2015, the FDATrusted Source declared that trans fat is not “generally recognized as safe” and had to be phased out by 2018.
5 -A recent study, published in The Lancet Diabetes & Endocrinology, evaluated for the first time the association between emulsifiers and the risk of developing type 2 diabete

A – Nutritional quality and costs of gluten-free products: a case-control study of food products on the Norwegian marked. 2021. Mari C. W. Myhrstad, Marlene Slydahl, Monica Hellmann, Lisa Garnweidner-Holme, Knut E. A. Lundin et al.

Background: Celiac disease is a chronic autoimmune disease triggered by gluten exposure in genetically predis- posed individuals. A life-long intake of a gluten-free (GF) diet is required for its management. Wheat, rye and barley are eliminated in a GF diet and the nutritional adequacy of the diet has been questioned. In Norway, cereals and bread constitute a key role of the diet and are the main source of fiber intake. Gluten restrictions may therefore offer important implications for nutrient adequacy especially linked to fiber intake in people with celiac disease.
Objective: The aim of the study was to investigate the nutritional quality and price of GF products and com- pare with gluten-containing counterparts available at instead of in the Norwegian market.

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The current study clearly shows that GF products compared to equivalent gluten-containing products contain less protein and fiber, and more carbohydrate, saturated fat and salt. Furthermore, GF compared to gluten-containing products are more expensive. To our knowledge, this is the first study comparing GF products at the Norwegian market with gluten-containing counterparts.

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B – Review on chemical composition of gluten-free food for celiac people. Antonella Maggio, Santino Orecchio and Salvatore Barreca. Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Università di Palermo, Viale delle Scienze, I-90128 Palermo, Italy. Integr Food Nutr Metab, 2019. Published: January 25, 2019.

Abtract: Gluten free food lead to possible nutrient unbalance resulting in improper nutritional quality of diet. The aim of this review is to show and discuss the composition of main components of common gluten free products in order to provide doctors and nutritionists the necessary data to compile balanced diets for users of gluten-free products and to determine their contribution to the daily intake of nutrients and micro elements. Special emphasis has been addressed to metal contents, fatty acid profiles and fibers.

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Conclusions
Most of the nutritional data reported in literature, are based on food labels. Few data were obtained by direct chemical analysis of food. In this context, will be necessary to encourage the use of chemical analytical practices in order to provide doctors and nutritionists the necessary data to compile balanced diets for users of gluten-free products and to determine their contribution to the daily intake of nutrients and micro elements. Special emphasis has been addressed to metal contents, fatty acid profiles and fibers.
Literature analysis has highlighted that, the most gluten free food, show a deficit of nutrients in term of concentrations. At this regard, an inadequate nutritional value of the GF-diet was observed from several authors. In detail, it was founded nutrient deficiencies for essential minerals such as iron, zinc magnesium and calcium, and on another hand high content of saturated lipids were detected.
Furthermore, the dietary-therapeutic approach should encourage the use of naturally gluten free products such as pseudo-cereals and fruits concerning to metal contents, and fish or seafood regarding fatty acids, especially for sutured and unsatured fatty acid ratio.
Moreover, alimentary education should become part of the therapeutic pathway to understand the importance of labels, choice of food and combination of macro and micronutrients.

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C – Fatty Acid Composition of Gluten-Free Food (Bakery Products) for Celiac People. Antonella Maggio and Santino Orecchio. Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Università di Palermo, Viale delle Scienze, I-90128 Palermo, Italy; antonella.maggio@unipa.it. Correspondence: santino.orecchio@unipa.it; Tel.: +39-91-2389-7968. Foods. Published: 20 June 2018

Abstract: The aim of this study (first analytical approach) was to obtain data concerning the fatty acid composition of gluten-free foods (bakery products) for celiac people. The study included 35 different products (snacks, biscuits, bakery products, pasta, flours, etc.) from several manufacturers. After extraction and esterification, the fatty acid composition was determined by Gaschromatography (GC–MS) Monounsaturated fatty acids (MUFAs) were found to be the major constituents (57%), followed by saturated fatty acids (SFAs) (30%), and polyunsaturated fatty acid (13%). Only 15 of the 35 gluten-free samples analyzed appeared to provide adequate energy intake, while, in 11 samples, saturated fatty acids were found to supply more energy than that recommended by the European Food Safety Authority EFSA. Moreover, data analyses showed that, although gluten-free commercial products are high added-value foods, industrial products in many cases contain palm and palm kernel oils, whereas the local producers generally use the finest raw materials, such as olive oil.

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D – Gluten-Free Products: Do We Need to Update Our Knowledge? Claudia Marmol-Soler. Foods 2022.
It can be concluded that reviewing the nutritional composition of GF foods from time to time is highly relevant since these products, which are in great demand, undergo constant changes in their composition with the aim of improving their nutritional quality. Despite improvements in the formulation of GFPs in recent years, their macronutrient profile suggested they contained marked differences and cannot be considered nutritionally equivalent when compared with their gluten-containing counterparts. Therefore, it is strongly recommended that food companies continue with the reformulation of these products in order to increase their nutritional quality, adapt to market demands, and accordingly provide balanced nutrition to those patients with CD.

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E – The truth about fats: the good, the bad, and the in-between
April 12, 2022. Avoid the trans fats, limit the saturated fats, and replace with essential polyunsaturated fats . Harvard Medical School. https://www.health.harvard.edu/

You may wonder isn’t fat bad for you, but your body needs some fat from food. It’s a major source of energy. It helps you absorb some vitamins and minerals. Fat is needed to build cell membranes, the vital exterior of each cell, and the sheaths surrounding nerves. It is essential for blood clotting, muscle movement, and inflammation. For long-term health, some fats are better than others. Good fats include monounsaturated and polyunsaturated fats. Bad ones include industrial-made trans fats. Saturated fats fall somewhere in the middle.
All fats have a similar chemical structure: a chain of carbon atoms bonded to hydrogen atoms. What makes one fat different from another is the length and shape of the carbon chain and the number of hydrogen atoms connected to the carbon atoms. Seemingly slight differences in structure translate into crucial differences in form and function.
Bad trans fats
The worst type of dietary fat is the kind known as trans fat. It is a byproduct of a process called hydrogenation that is used to turn healthy oils into solids and to prevent them from becoming rancid. Trans fats have no known health benefits and that there is no safe level of consumption. Therefore, they have been officially banned in the United States.
Early in the 20thcentury, trans fats were found mainly in solid margarines and vegetable shortening. As food makers learned new ways to use partially hydrogenated vegetable oils, they began appearing in everything from commercial cookies and pastries to fast-food French fries. Trans fats are now banned in the U.S. and many other countries.
Eating foods rich in trans fats increases the amount of harmful LDL cholesterol in the bloodstream and reduces the amount of beneficial HDL cholesterol. Trans fats create inflammation, which is linked to heart disease, stroke, diabetes, and other chronic conditions. They contribute to insulin resistance, which increases the risk of developing type 2 diabetes. Even small amounts of trans fats can harm health: for every 2% of calories from trans fat consumed daily, the risk of heart disease rises by 23%.

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F- Hydrogenated oil comes in two forms: partially or fully hydrogenated. One use of hydrogenated oil is to preserve the shelf life of food. Partially hydrogenated oil contains trans fat that can raise cholesterol and result in health complications. Food manufacturers use hydrogenated oil as a preservative. They also use it for enhancing flavor and texture.
In 2015, the Food and Drug Administration (FDA)Trusted Source said that partially hydrogenated oil is not safe, and removing it from food could prevent thousands of heart attacks each year.
Partially hydrogenated oil (trans fat)
In the past, manufacturers added partially hydrogenated oils to processed foods.
According to the FDA, foods that used to contain large amounts of artificial trans fat include:
most baked goods
stick margarine
frosting
coffee creamers
snack foods
In 2015, the FDATrusted Source declared that trans fat is not “generally recognized as safe” and had to be phased out by 2018.
However, trans fat may still be present in some foods. According to the American Heart Association (AHA)Trusted Source, trans fat occurs naturally in certain animals, such as cows.
Fully hydrogenated oil
Fully hydrogenated oil also uses a process to take a liquid oil and transform it into a solid at room temperature. As the name suggests, the oil is fully or nearly completely hydrogenated, which reduces the amount of trans fat in the final product. Unlike partially hydrogenated oil, the FDATrusted Source still allow products to use fully hydrogenated oil as of 2018. In 2020, the FDA released certification that states fully hydrogenated rapeseed oil is safe for sparing use in food products. Though hydrogenated oils may be safe, it does not mean they are necessarily good for a person to consume. Products that contain them are often highly processed with added sugar and salt.
From: https://www.medicalnewstoday.com/articles/325266#summary

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G- Nutritional quality and costs of gluten-free products: a case-control study of food products on the Norwegian market. Mari C.W. Myhrstad et al. 2021
Results: The GF products contained less protein and fier, and higher content of saturated fat, carbohydrate and salt compared to the gluten-containing products. The total amount of fat was not different between the groups. A similar pattern was found within several of the food categories. More gluten-containing products met the nutrition claim “high in fier” (fiber > 6 g/100 g) compared to the GF products. The price of the GF products was higher; ranging from 46%–443% more expensive than the gluten-containing products.

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H – Macchine alimentari – Prodotti e tecnologie per alimenti senza glutine. Anno XVII -1 – Genn. Feb 2015
Idrocolloidi. (H1) Tra le ultime novità che possono soddisfare queste esigenze troviamo, come sopra citati, gli idrocolloidi, che si stanno affermando con maggiore forza nel settore bakery. Queste sostanze, infatti, permettono di ottenere prodotti con lunga shelf life, inserimento di farine integrali e fibre, l’assenza di grassi trans e non ultimo l’assenza di glutine. Gli idrocolloidi, come il termine fa presagire, sono molecole in grado di legare acqua in grandi quantità; tra i più usati nei prodotti da forno vi sono la gomma di xantano, la pectina, le cellulose modificate e i frutto- e galatto-oligosaccaridi. Alcune di queste sostanze sono considerate fibre alimentari, in grado di stimolare il senso di sazietà e avere effetti positivi sulla funzionalità intestinale: la loro presenza si può configurare, pertanto, co- me aggiunta di sostanze benefiche al prodotto. Spesso gli idrocolloidi ottengono il loro effetto tecnologico-funzionale nel prodotto anche se aggiunti agli impasti in piccole quantità, per esempio minori dell’1% del totale degli ingredienti in polvere. Negli impasti di pane e altri prodotti da forno gli idrocolloidi aiutano, in fase produttiva, a migliorare la lavorabilità dell’impasto grazie all’effetto di rapida ed uniforme idratazione dello stesso. Il volume, la struttura e la sofficità dei prodotti finiti sono migliorati. La fragilità è minore, per esempio nel caso di prodotti da forno “spumosi” con elevata presenza di bolle d’aria o presenza di pezzi in sospensione (cioccolato, frutta o frutta secca): tali bolle o pezzi sono stabilizzati all’interno del sistema grazie agli idrocolloidi. In fase di conservazione, poi, c’è un aumento della shelf life dei prodotti grazie al mantenimento di sofficità per tempi più prolungati: la differenza rispetto ai prodotti privi di idrocolloidi è tanto più evidente con il passare del tempo. Pare, infine, che la presenza di idrocolloidi sia anche in grado di influenzare le dimensioni dei cristalli di ghiaccio all’interno degli impasti per pane o altri prodotti semi-cotti durante la loro surgelazione, permettendo di ottenere un prodotto scongelato di migliore qualità.
Omissis…
(H2) Ci sono operazioni unitarie che sono di difficile attuazione per alimenti che non prevedono l’uso di glutine, come per esempio le fasi di estrusione, trafilatura o laminazione che avvengono nella pasta oppure in alcuni prodotti da forno: le sollecitazioni che avvengono in queste fasi necessitano di elasticità da parte dell’impasto, pertanto sono fondamentali formulazioni in grado di sostenere il processo in continuo di un impianto magari pre-esistente.
Omissis….
(H3) Se si confrontano dei cracker senza glutine, si riscontrano formulazioni estremamente semplici, con farine di mais e riso, ed altre più complesse, con l’aggiunta di fecola di patate, destrosio, emulsionanti ed addensanti. Dal punto di vista nutrizionale, è chiaro che l’alimento potrebbe risultare, rispetto al medesimo prodotto convenzionale, maggiormente ricco di zuccheri ed in parte di grassi. Il pane in cassetta, più difficile da realizzare in quanto lievitato, mostra formulazioni piuttosto complesse a base di mais, riso o grano saraceno, amidi, fibre vegetali, proteine, zuccheri, addensanti (tra cui idrocolloidi), emulsionanti, acidificanti. Tale ricettazione implica, a livello nutrizionale, o un aumento di carboidrati di circa il 10- 15% rispetto al prodotto convenzionale della medesima categoria oppure un aumento di grassi, soprattutto saturi, di circa il 30-50%.
Nel campo dolciario, le considerazioni sono più o meno le medesime, in quanto a livello nutrizio- nale, rispetto ai prodotti convenzionali, permangono valori più elevati di carboidrati, soprattutto zuccheri, e grassi, principalmente saturi, per sop- perire alla carenza di viscoelasticità della parte proteica.

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I – Emulsionanti e rischio diabete: lo studio di Lancet
Dopo essere stati accusati di contribuire al rischio di obesità, cancro e malattie cardiovascolari, un’analisi recente condotta sullo studio prospettico di coorte NutriNet Santé li identifica come fattori che aumentano il rischio di diabete di tipo 2.
Sebbene le Autorità Sanitarie considerino sicuro il loro uso in quantità definite, basandosi su criteri di citotossicità e genotossicità, di recente stanno emergendo prove dei loro effetti negativi sul microbiota intestinale, che a sua volta innescano infiammazione e alterazioni metaboliche.
Un recente studio, pubblicato su The Lancet Diabetes & Endocrinology ha valutato per la prima volta l’associazione tra emulsionanti e rischio di sviluppare diabete di tipo 2. Gli Autori hanno analizzato i dati di oltre 104 mila adulti arruolati dal 2009 al 2023 a cui è stato chiesto di compilare registri dietetici di 24 ore ogni 6 mesi. L’obiettivo era valutare l’esposizione agli emulsionanti.
L’1% del campione, ha sviluppato diabete di tipo 2 durante il follow up di 6-8 anni.
Dei 61 additivi identificati, sono sette gli emulsionanti ‘attenzionati’ associati a un potenziale aumento del rischio di diabete (occhi, quindi, alle etichette!):
E407 (carragenine totali);
E340 (esteri di poliglicerolo);
E472e (esteri di acidi grassi);
E331 (citrato di sodio);
E412 (gomma di guar);
E414 (gomma arabica);
E415 (gomma di xantano);
oltre ad un gruppo chiamato ‘carragenine’.
Gli additivi emulsionanti sono stati assunti nel 5% da frutta e verdure ultra lavorate (come verdure in scatola e frutta sciroppata), nel 14.7% da torte e biscotti, nel 10% da prodotti lattiero-caseari.
Tre conseguenze sottolineate dal prof. Angelo Avogaro, Presidente SID
1. La necessità di contenere il consumo di cibi ultra-processati;
2. l’appello a una maggiore attenzione alle etichette;
3. la necessità di chiedere una regolamentazione più stringente allo scopo di proteggere i consumatori.
“Sebbene siano necessari ulteriori studi a lungo termine, le alterazioni del microbiota intestinale, fanno ritenere che potrebbe essere necessario rivedere gli RDA (Recommended Daily Allowance, livelli giornalieri di assunzione). Precedenti prove che legavano l’assunzione di carragenina all’infiammazione intestinale hanno portato l’JECFA a limitarne l’uso nelle formule e negli alimenti per neonati. Stiamo assistendo a un preoccupante aumento del diabete di tipo 2 anche tra bambini e adolescenti” sottolinea la Prof.ssa Raffaella Buzzetti, Presidente eletto SID.
References
Food additive emulsifiers and the risk of type 2 diabetes: analysis of data from the NutriNet-Santé prospective cohort study. The Lancet Diabete and Endocrinology, volume 12, issue 5, p339-349, May 2024