Contrasted central effects of n-3 versus n-6 diets on brain functions in diet-induced obesity in minipigs.

INTRODUCTION: N3 polyunsaturated fatty acids (n-3 PUFAs) exert anti-inflammatory effects for the hypothalamus, but their extra-hypothalamic outcome lack documentation. We evaluated the central consequences of the substitution of saturated fatty acids with n-3 or n-6 PUFA in obesogenic diets. METHODS: Twenty-one miniature pigs were fed ad libitum obesogenic diets enriched in fat provided either as lard, fish oil (source for n-3 PUFAs), or sunflower oil (source for n-6 PUFAs) for ten weeks. The blood-brain barrier (BBB) permeability was quantified by CT perfusion. Central autonomic network was evaluated using heart rate variability, and PET 18FDG was performed to assess brain metabolism. RESULTS: BBB permeability was higher in lard group, but heart rate variability changed only in fish oil group. Brain connectivity analysis and voxel-based comparisons show regional differences between groups except for the cingulate cortex in fish oil vs. sunflower oil groups. DISCUSSION: : The minute changes in brain metabolism in obese pigs feed with fish oil compared with saturated fatty acids were sufficient to induce detrimental changes in heart rate variability. On the contrary, the BBB's decreased permeability in n-3 and n-6 PUFAs groups was protective against an obesity-driven damaged BBB.

Recent advances in intestinal alkaline phosphatase, inflammation, and nutrition.

In recent years, much new data on intestinal alkaline phosphatase (IAP) have been published, and major breakthroughs have been disclosed. The aim of the present review is to critically analyze the publications released over the last 5 years. These breakthroughs include, for example, the direct implication of IAP in intestinal tight junction integrity and barrier function maintenance; chronic intestinal challenge with low concentrations of Salmonella generating long-lasting depletion of IAP and increased susceptibility to inflammation; the suggestion that genetic mutations in the IAP gene in humans contribute to some forms of chronic inflammatory diseases and loss of functional IAP along the gut and in stools; stool IAP as an early biomarker of incipient diabetes in humans; and omega-3 fatty acids as direct inducers of IAP in intestinal tissue. Many recent papers have also explored the prophylactic and therapeutic potential of IAP and other alkaline phosphatase (AP) isoforms in various experimental settings and diseases. Remarkably, nearly all data confirm the potent anti-inflammatory properties of (I)AP and the negative consequences of its inhibition on health. A simplified model of the body AP system integrating the IAP compartment is provided. Finally, the list of nutrients and food components stimulating IAP has continued to grow, thus emphasizing nutrition as a potent lever for limiting inflammation.

Biology, environmental and nutritional modulation of skin mucus alkaline phosphatase in fish: A review.

Alkaline phosphatase (AP) is a major, recently recognized component of innate immunity. The intestinal AP (IAP) isoform plays a pivotal role in controlling gastrointestinal and systemic inflammation in terrestrial mammals. This is so essentially through detoxification (by dephosphorylation) of proinflammatory microbial components that can no longer be recognized by so-called toll-like receptors, thus preventing cellular inflammatory cascade activation. A unique feature of fish is the presence of AP in skin and epidermal mucus (skin mucus AP) but its actual functions and underlying mechanisms of action are presently unknown. Here, we gather and analyse knowledge available on skin mucus AP in order to provide a holistic view of this important protective enzyme. Our main conclusions are that skin mucus AP is responsive to biotic and abiotic factors, including nutrients and bioactive feed components, prebiotics and probiotics. Importantly, both skin mucus AP and IAP appear to correlate, thus raising the interesting possibility that skin mucus AP be used as a proxy for IAP in future nutritional studies. Blood serum AP also seems to correlate with skin mucus AP, though biological interpretation for such relationship is presently unknown. Finally, the precise isoform/s of AP present in skin should be identified and underlying molecular mechanisms of skin mucus AP actions deciphered.

Oral sodium butyrate impacts brain metabolism and hippocampal neurogenesis, with limited effects on gut anatomy and function in pigs.

Butyrate can improve gut functions, whereas histone deacetylase inhibitors might alleviate neurocognitive alterations. Our aim was to assess whether oral butyrate could modulate brain metabolism and plasticity and if this would relate to gut function. Sixteen pigs were subjected to sodium butyrate (SB) supplementation via beverage water or water only [control (C)]. All pigs had blood sampled after 2 and 3 wk of treatment, and were subjected to a brain positron emission tomography after 3 wk. Animals were euthanized after 4 wk to sample pancreas, intestine, and brain for gut physiology and anatomy measurements, as well as hippocampal histology, Ki67, and doublecortin (DCX) immunohistochemistry. SB compared with C treatment triggered basal brain glucose metabolism changes in the nucleus accumbens and hippocampus ( P = 0.003), increased hippocampal granular cell layer volume ( P = 0.006), and neurogenesis (Ki67: P = 0.026; DCX: P = 0.029). After 2 wk of treatment, plasma levels of glucose, insulin, lactate, glucagon-like peptide 1, and peptide tyrosine tyrosine remained unchanged. After 3 wk, plasma levels of lactate were lower in SB compared with C animals ( P = 0.028), with no difference for glucose and insulin. Butyrate intake impacted very little gut anatomy and function. These results demonstrate that oral SB impacted brain functions with little effects on the gut.-Val-Laillet, D., Guérin, S., Coquery, N., Nogret, I., Formal, M., Romé, V., Le Normand, L., Meurice, P., Randuineau, G., Guilloteau, P., Malbert, C.-H., Parnet, P., Lallès, J.-P., Segain, J.-P. Oral sodium butyrate impacts brain metabolism and hippocampal neurogenesis, with limited effects on gut anatomy and function in pigs.

Case studies on genetically modified organisms (GMOs): Potential risk scenarios and associated health indicators.

Within the frame of the EU-funded MARLON project, background data were reviewed to explore the possibility of measuring health indicators during post-market monitoring for potential effects of feeds, particularly genetically modified (GM) feeds, on livestock animal health, if applicable. Four case studies (CSs) of potential health effects on livestock were framed and the current knowledge of a possible effect of GM feed was reviewed. Concerning allergenicity (CS-1), there are no case-reports of allergic reactions or immunotoxic effects resulting from GM feed consumption as compared with non-GM feed. The likelihood of horizontal gene transfer (HGT; CS-2) of GMO-related DNA to different species is not different from that for other DNA and is unlikely to raise health concerns. Concerning mycotoxins (CS-3), insect-resistant GM maize may reduce fumonisins contamination as a health benefit, yet other Fusarium toxins and aflatoxins show inconclusive results. For nutritionally altered crops (CS-4), the genetic modifications applied lead to compositional changes which require special considerations of their nutritional impacts. No health indicators were thus identified except for possible beneficial impacts of reduced mycotoxins and nutritional enhancement. More generally, veterinary health data should ideally be linked with animal exposure information so as to be able to establish cause-effect relationships.

Microbiota-host interplay at the gut epithelial level, health and nutrition.

Growing evidence suggests the implication of the gut microbiota in various facets of health and disease. In this review, the focus is put on microbiota-host molecular cross-talk at the gut epithelial level with special emphasis on two defense systems: intestinal alkaline phosphatase (IAP) and inducible heat shock proteins (iHSPs). Both IAP and iHSPs are induced by various microbial structural components (e.g. lipopolysaccharide, flagellin, CpG DNA motifs), metabolites (e.g. n-butyrate) or secreted signal molecules (e.g., toxins, various peptides, polyphosphate). IAP is produced in the small intestine and secreted into the lumen and in the interior milieu. It detoxifies microbial components by dephosphorylation and, therefore, down-regulates microbe-induced inflammation mainly by inhibiting NF-κB pro-inflammatory pathway in enterocytes. IAP gene expression and enzyme activity are influenced by the gut microbiota. Conversely, IAP controls gut microbiota composition both directly, and indirectly though the detoxification of pro-inflammatory free luminal adenosine triphosphate and inflammation inhibition. Inducible HSPs are expressed by gut epithelial cells in proportion to the microbial load along the gastro-intestinal tract. They are also induced by various microbial components, metabolites and secreted molecules. Whether iHSPs contribute to shape the gut microbiota is presently unknown. Both systems display strong anti-inflammatory and anti-oxidant properties that are protective to the gut and the host. Importantly, epithelial gene expressions and protein concentrations of IAP and iHSPs can be stimulated by probiotics, prebiotics and a large variety of dietary components, including macronutrients (protein and amino acids, especially L-glutamine, fat, fiber), and specific minerals (e.g. calcium) and vitamins (e.g. vitamins K1 and K2). Some food components (e.g. lectins, soybean proteins, various polyphenols) may inhibit or disturb these systems. The general cellular and molecular mechanisms involved in the microbiota-host epithelial crosstalk and subsequent gut protection through IAP and iHSPs are reviewed along with their nutritional modulation. Special emphasis is also given to the pig, an economically important species and valuable biomedical model.

Obesogenic diets have deleterious effects on fat deposits irrespective of the nature of dietary carbohydrates in a Yucatan minipig model.

The effects of digestible carbohydrates, fructose in particular, on the development of metabolic disturbances remain controversial. We explored the effects of prolonged consumption of high-fat diets differing in their carbohydrate source on fat deposits in the adult Yucatan minipig. Eighteen minipigs underwent computed tomographic imaging and blood sampling before and after 8 weeks of three isocaloric high-fat diets with different carbohydrate sources (20% by weight for starch in the control diet, glucose or fructose, n=6 per diet). Body adiposity, liver volume, and fat content were estimated from computed tomographic images (n=18). Liver volume and lipid content were also measured post mortem (n=12). We hypothesized that the quantity and the spatial distribution of fat deposits in the adipose tissue or in the liver would be altered by the nature of the carbohydrate present in the obesogenic diet. After 8 weeks of dietary exposure, body weight (from 26±4 to 58±3 kg), total body adiposity (from 38±1 to 47±1%; P<.0001), liver volume (from 1156±31 to 1486±66 mL; P<.0001), plasma insulin (from 10±1 to 14±2 mIU/L; P=.001), triacylglycerol (from 318±37 to 466±33 mg/L; P=.005), and free-fatty acids (from 196±60 to 396±59 µmol/L; P=.0001) increased irrespective of the carbohydrate type. Similarly, the carbohydrate type did not induce changes in the spatial repartition of the adipose tissue. Divergent results were obtained for fat deposits in the liver depending on the investigation method. In conclusion, obesogenic diets alter adipose tissue fat deposits and the metabolic profile independently of the nature of dietary carbohydrates.

Dairy products and the French paradox: Could alkaline phosphatases play a role?

The French paradox - high saturated fat consumption but low incidence of cardiovascular disease (CVD) and mortality - is still unresolved and continues to be a matter of debate and controversy. Recently, it was hypothesised that the high consumption of dairy products, and especially cheese by the French population might contribute to the explanation of the French paradox, in addition to the "(red) wine" hypothesis. Most notably this would involve milk bioactive peptides and biomolecules from cheese moulds. Here, we support the "dairy products" hypothesis further by proposing the "alkaline phosphatase" hypothesis. First, intestinal alkaline phosphatase (IAP), a potent endogenous anti-inflammatory enzyme, is directly stimulated by various components of milk (e.g. casein, calcium, lactose and even fat). This enzyme dephosphorylates and thus detoxifies pro-inflammatory microbial components like lipopolysaccharide, making them unable to trigger inflammatory responses and generate chronic low-grade inflammation leading to insulin resistance, glucose intolerance, type-2 diabetes, metabolic syndrome and obesity, known risk factors for CVD. Various vitamins present in high amounts in dairy products (e.g. vitamins A and D; methyl-donors: folate and vitamin B12), and also fermentation products such as butyrate and propionate found e.g. in cheese, all stimulate intestinal alkaline phosphatase. Second, moulded cheeses like Roquefort contain fungi producing an alkaline phosphatase. Third, milk itself contains a tissue nonspecific isoform of alkaline phosphatase that may function as IAP. Milk alkaline phosphatase is present in raw milk and dairy products increasingly consumed in France. It is deactivated by pasteurization but it can partially reactivate after thermal treatment. Experimental consolidation of the "alkaline phosphatase" hypothesis will require further work including: systematic alkaline phosphatase activity measurements in dairy products, live dairy ferments and intestine of model animals. Furthermore, stool residual IAP, a possible early marker of diabetes, should be assayed in human cohorts. If confirmed, this "alkaline phosphatase" hypothesis will highlight the protective effects of milk alkaline phosphatase and promote the consumption of (microbiologically safe) raw milk and dairy products. Microorganisms secreting alkaline phosphatases may be privileged as ferments in dairy products.

Critical review evaluating the pig as a model for human nutritional physiology.

The present review examines the pig as a model for physiological studies in human subjects related to nutrient sensing, appetite regulation, gut barrier function, intestinal microbiota and nutritional neuroscience. The nutrient-sensing mechanisms regarding acids (sour), carbohydrates (sweet), glutamic acid (umami) and fatty acids are conserved between humans and pigs. In contrast, pigs show limited perception of high-intensity sweeteners and NaCl and sense a wider array of amino acids than humans. Differences on bitter taste may reflect the adaptation to ecosystems. In relation to appetite regulation, plasma concentrations of cholecystokinin and glucagon-like peptide-1 are similar in pigs and humans, while peptide YY in pigs is ten to twenty times higher and ghrelin two to five times lower than in humans. Pigs are an excellent model for human studies for vagal nerve function related to the hormonal regulation of food intake. Similarly, the study of gut barrier functions reveals conserved defence mechanisms between the two species particularly in functional permeability. However, human data are scant for some of the defence systems and nutritional programming. The pig model has been valuable for studying the changes in human microbiota following nutritional interventions. In particular, the use of human flora-associated pigs is a useful model for infants, but the long-term stability of the implanted human microbiota in pigs remains to be investigated. The similarity of the pig and human brain anatomy and development is paradigmatic. Brain explorations and therapies described in pig, when compared with available human data, highlight their value in nutritional neuroscience, particularly regarding functional neuroimaging techniques.

Gut epithelial inducible heat-shock proteins and their modulation by diet and the microbiota.

The epidemic of metabolic diseases has raised questions about the interplay between the human diet and the gut and its microbiota. The gut has two vital roles: nutrient absorption and intestinal barrier function. Gut barrier defects are involved in many diseases. Excess energy intake disturbs the gut microbiota and favors body entry of microbial compounds that stimulate chronic metabolic inflammation. In this context, the natural defense mechanisms of gut epithelial cells and the potential to boost them nutritionally warrant further study. One such important defense system is the activation of inducible heat-shock proteins (iHSPs) which protect the gut epithelium against oxidative stress and inflammation. Importantly, various microbial components can induce the expression of iHSPs. This review examines gut epithelial iHSPs as the main targets of microbial signals and nutrients and presents data on diseases involving disturbances of gut epithelial iHSPs. In addition, a broad literature analysis of dietary modulation of gut epithelial iHSPs is provided. Future research aims should include the identification of gut microbes that can optimize gut-protective iHSPs and the evaluation of iHSP-mediated health benefits of nutrients and food components.

Nonalcoholic fatty liver disease: Roles of the gut and the liver and metabolic modulation by some dietary factors and especially long-chain n-3 PUFA.

Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is the leading cause of chronic liver disease in Western countries. NASH increases the risk for fibrosis, cirrhosis, and hepatocellular carcinoma. The mechanisms underlying the steatosis to NASH transition remain incompletely understood despite recent progress in cellular and molecular aspects. Our primary aim is to analyze recent advances in understanding deviations in hepatic fat metabolism and the implication of gut physiology and microbiota in this transition. Our second aim is to gather experimental and clinical data on the capability of long-chain n-3 PUFA (LC n-3 PUFA), including docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids to prevent or alleviate NAFLD. Our main conclusions are: (i) increasing data support a pivotal role for the gut toward NASH development; (ii) LC n-3 PUFA have often proven preventive or therapeutic effect toward NASH development in rodent models. In patients with NASH they appear to have no therapeutic effects, but they could have preventive effects, which require to define better the specific roles, modes of action, and doses of DHA and EPA.

The Olfactory Receptor OR51E1 Is Present along the Gastrointestinal Tract of Pigs, Co-Localizes with Enteroendocrine Cells and Is Modulated by Intestinal Microbiota.

UNLABELLED: The relevance of the butyrate-sensing olfactory receptor OR51E1 for gastrointestinal (GIT) functioning has not been considered so far. We investigated in young pigs the distribution of OR51E1 along the GIT, its relation with some endocrine markers, its variation with age and after interventions affecting the gut environment and intestinal microbiota. Immuno-reactive cells for OR51E1 and chromogranin A (CgA) were counted in cardial (CA), fundic (FU), pyloric (PL) duodenal (DU), jejunal (JE), ileal (IL), cecal (CE), colonic (CO) and rectal (RE) mucosae. OR51E1 co-localization with serotonin (5HT) and peptide YY (PYY) were evaluated in PL and CO respectively. FU and PL tissues were also sampled from 84 piglets reared from sows receiving either or not oral antibiotics (amoxicillin) around parturition, and sacrificed at days 14, 21, 28 (weaning) and 42 of age. JE samples were also obtained from 12 caesarean-derived piglets that were orally associated with simple (SA) or complex (CA) microbiota in the postnatal phase, and of which on days 26-37 of age jejunal loops were perfused for 8 h with enterotoxigenic Escherichia coli F4 (ETEC), Lactobacillus amylovorus or saline (CTRL). Tissue densities of OR51E1+ cells were in decreasing order: PL=DU>FU=CA>JE=IL=CE=CO=RE. OR51E1+ cells showed an enteroendocrine nature containing gastrointestinal hormones such as PYY or 5HT. OR51E1 gene expression in PL and FU increased during and after the suckling period (p<0.05). It was marginally reduced in offspring from antibiotic-treated sows (tendency, p=0.073), vs. CONTROL: Jejunal OR51E1 gene expression was reduced in piglets early associated with SA, compared with CA, and in ETEC-perfused loops vs. CTRL (p<0.01). Our results indicate that OR51E1 is related to GIT enteroendocrine activity. Moreover age, pathogen challenge and dietary manipulations influencing the gastrointestinal luminal microenvironment significantly affect the OR51E1 gene expression in GIT tissues presumably in association with the release of microbial metabolites.

Maternal antibiotic-induced early changes in microbial colonization selectively modulate colonic permeability and inducible heat shock proteins, and digesta concentrations of alkaline phosphatase and TLR-stimulants in swine offspring.

Elevated intake of high energy diets is a risk factor for the development of metabolic diseases and obesity. High fat diets cause alterations in colonic microbiota composition and increase gut permeability to bacterial lipopolysaccharide, and subsequent low-grade chronic inflammation in mice. Chronic inflammatory bowel diseases are increasing worldwide and may involve alterations in microbiota-host dialog. Metabolic disorders appearing in later life are also suspected to reflect changes in early programming. However, how the latter affects the colon remains poorly studied. Here, we hypothesized that various components of colonic physiology, including permeability, ion exchange and protective inducible heat shock proteins (HSP) are influenced in the short- and long-terms by early disturbances in microbial colonization. The hypothesis was tested in a swine model. Offspring were born to control mothers (n = 12) or mothers treated with the antibiotic (ATB) amoxicillin around parturition (n = 11). Offspring were slaughtered between 14 and 42 days of age to study short-term effects. For long-term effects, young adult offspring from the same litters consumed a normal or a palm oil-enriched diet for 4 weeks between 140 and 169 days of age. ATB treatment transiently modified maternal fecal microbiota although the minor differences observed for offspring colonic microbiota were nonsignificant. In the short-term, consistently higher HSP27 and HSP70 levels and transiently increased horseradish peroxidase permeability in ATB offspring colon were observed. Importantly, long-term consequences included reduced colonic horseradish peroxidase permeability, and increased colonic digesta alkaline phosphatase (AP) and TLR2- and TLR4-stimulant concentrations in rectal digesta in adult ATB offspring. Inducible HSP27 and HSP70 did not change. Interactions between early ATB treatment and later diet were noted for paracellular permeability and concentrations of colonic digesta AP. In conclusion, our data suggest that early ATB-induced changes in bacterial colonization modulate important aspects of colonic physiology in the short- and long-terms.

Dietary sugars: their detection by the gut-brain axis and their peripheral and central effects in health and diseases.

BACKGROUND: Substantial increases in dietary sugar intake together with the increasing prevalence of obesity worldwide, as well as the parallels found between sugar overconsumption and drug abuse, have motivated research on the adverse effects of sugars on health and eating behaviour. Given that the gut-brain axis depends on multiple interactions between peripheral and central signals, and because these signals are interdependent, it is crucial to have a holistic view about dietary sugar effects on health. METHODS: Recent data on the effects of dietary sugars (i.e. sucrose, glucose, and fructose) at both peripheral and central levels and their interactions will be critically discussed in order to improve our understanding of the effects of sugars on health and diseases. This will contribute to the development of more efficient strategies for the prevention and treatment for obesity and associated co-morbidities. RESULTS: This review highlights opposing effects of glucose and fructose on metabolism and eating behaviour. Peripheral glucose and fructose sensing may influence eating behaviour by sweet-tasting mechanisms in the mouth and gut, and by glucose-sensing mechanisms in the gut. Glucose may impact brain reward regions and eating behaviour directly by crossing the blood-brain barrier, and indirectly by peripheral neural input and by oral and intestinal sweet taste/sugar-sensing mechanisms, whereas those promoted by fructose orally ingested seem to rely only on these indirect mechanisms. CONCLUSIONS: Given the discrepancies between studies regarding the metabolic effects of sugars, more studies using physiological experimental conditions and in animal models closer to humans are needed. Additional studies directly comparing the effects of sucrose, glucose, and fructose should be performed to elucidate possible differences between these sugars on the reward circuitry.

Fosfatasa alcalina intestinal: una enzima con propiedades antiinflamatorias / Intestinal alkaline phosphatase: an enzyme with anti-inflammatory properties / Fosfatasse alcalina intestinal: uma enzima com propriedades anti-inflamatórias

Resumen Una de las principales funciones de la Fosfatasa Alcalina Intestinal (FAI) es la detoxificación de los lipopolisacáridos (LPS) bacterianos para controlar la inflamación intestinal. Recientes publicaciones indican que FAI participa en la detoxificación de otros compuestos bacterianos (flagelina y motivos CpG de DNA) y de muchos nucleótidos libres (ATP, UDP). FAI está involucrada de manera directa en la recuperación tisular de la inflamación por la Resolvina E1. La acción antiinflamatoria de FAI mejora indirectamente la función de la barrera intestinal e impacta la diversidad y la composición de la microbiota. Diversas enfermedades intestinales, incluyendo enterocolitis necrótica, enfermedad celíaca y la inflamación crónica intestinal (o inflammatory bowel disease, IBD) están relacionadas con disminuciones en la expresión y actividad de FAI. Por otro lado, una elevada actividad de FAI en colon es sinónimo de procesos inflamatorios, debido a la elevada concentración de la isoforma tisular de Fosfatasa Alcalina no específica (FANE), y a la infiltración tisular por los neutrófilos (que también contienen FANE). En algunos ensayos en humanos se ha observado que la administración exógena de FAI reduce la inflamación intestinal/sistémica (dependiendo de la vía de administración). En conclusión, la homeóstasis intestinal y la preservación de la salud dependen en gran medida de la capacidad de FAI para detoxificar los LPS y suprimir la inflamación metabólica inducida por estos. Sin embargo, es necesario realizar investigaciones a fondo sobre como los hábitos alimenticios pueden modificar la detoxificación de los diferentes compuestos proinflamatorios bacterianos y maximizar la actividad de FAI.

Abstract One of the main functions of Intestinal Alkaline Phosphatase (FAI) is to detoxify bacterial lipopolysaccharides (LPS) to control intestinal inflammation. Recent data indicate that FAI participates in the detoxification of other bacterial compounds (flagellin and DNA CpG motifs) and many free nucleotides (ATP, UDP). FAI is directly involved in the resolution of tissue inflammation mediated by Resolvin E1. The anti-inflammatory action of FAI indirectly improves the intestinal barrier function and affects the diversity of microbiota. Various intestinal diseases, including necrotizing enterocolitis, celiac disease and chronic intestinal inflammation (inflammatory bowel disease) are related to a decrease in the expression and activity of FAI. Furthermore, a high FAI activity in the colon is related with inflammatory processes due to high concentration of tissue nonspecific alkaline phosphatase isoform (FANE) and tissue infiltration by neutrophils, which also contain FANE. Exogenous administration of FAI reduces intestinal and/or systemic inflammation (depending on the route of administration). In conclusion, intestinal homeostasis and health largely depend on the capacity of FAI to detoxify LPS and remove LPS-induced metabolic inflammation. However, how our diets can actually limit gut pools of pro-inflammatory bacterial compounds and maximize IAP activity needs more in-depth investigations.

Resumo Uma das principais funções da Fosfatasse Alcalina Intestinal (FAI) é a detoxificação dos lipopolissacarídeos (LPS) bacterianos para controlar a inflamação intestinal. Recentes publicações indicam que a FAI participa na detoxificação de outros compostos bacterianos (flagelina e motivos CpG do DNA) e de muitos nucleotídeos libres (ATP, UDP). A FAI está involucrada de forma direita na recuperação tissular da inflamação pela Resolvina E1 (RvE1). A ação antiinflamatória da FAI melhora indiretamente a função da barreira intestinal e impacta a diversidade e a composição da microbiota. Diversas doenças intestinais, incluindo enterocolitis necrótica, doença celíaca e a inflamação crônica intestinal (inflammatory bowel disease, IBD) estão relacionados com diminuições na expressão e atividade da FAI. De outro jeito, uma elevada atividade da FAI no cólon é sinônimo de processos inflamatórios, devido a elevada concentração da isoforma tissular da Fosfatasse Alcalina não especifica (FANE), e a infiltração tissular pelos neutrófilos (que também contém FANE). A administração exógena da FAI reduz a inflamação intestinal/sistêmica (dependendo da via de administração) incluindo uns poucos testes no homem. Em conclusão, a homeostase intestinal e a preservação da saúde dependem em grande medida da capacidade da FAI para detoxificar os LPS e suprimir a inflamação metabólica induzida por estes. Embora, é preciso realizar pesquisas bem feitas sobre como os costumes alimentares podem modificar a detoxificação dos diferentes compostos proinflamatórios bacterianos e maximizar a.

Intestinal alkaline phosphatase: novel functions and protective effects.

Important protective roles of intestinal alkaline phosphatase (IAP)--including regulation of intestinal surface pH, absorption of lipids, detoxification of free nucleotides and bacterial lipopolysaccharide, attenuation of intestinal inflammation, and possible modulation of the gut microbiota--have been reviewed recently. IAP is modulated by numerous nutritional factors. The present review highlights new findings on the properties of IAP and extends the list of its protective functions. Critical assessment of data suggests that some IAP properties are a direct result of dephosphorylation of proinflammatory moieties, while others (e.g., gut barrier protection and microbiota shaping) may be secondary to IAP-mediated downregulation of inflammation. IAP and tissue-nonspecific alkaline phosphatase isoforms characterize the small intestine and the colon, respectively. Gastrointestinal administration of exogenous IAP ameliorates gut inflammation and favors gut tissue regeneration, whereas enteral and systemic IAP administration attenuates systemic inflammation only. Finally, the IAP gene family has a strong evolutionary link to food-driven changes in gastrointestinal tract anatomy and microbiota composition. Therefore, stimulation of IAP activity by dietary intervention is a goal for preserving gut homeostasis and health by minimizing low-grade inflammation.

Early changes in microbial colonization selectively modulate intestinal enzymes, but not inducible heat shock proteins in young adult Swine.

Metabolic diseases and obesity are developing worldwide in a context of plethoric intake of high energy diets. The intestine may play a pivotal role due to diet-induced alterations in microbiota composition and increased permeability to bacterial lipopolysaccharide inducing metabolic inflammation. Early programming of metabolic disorders appearing in later life is also suspected, but data on the intestine are lacking. Therefore, we hypothesized that early disturbances in microbial colonization have short- and long-lasting consequences on selected intestinal components including key digestive enzymes and protective inducible heat shock proteins (HSP). The hypothesis was tested in swine offspring born to control mothers (n = 12) or mothers treated with the antibiotic amoxicillin around parturition (n = 11), and slaughtered serially at 14, 28 and 42 days of age to assess short-term effects. To evaluate long-term consequences, young adult offspring from the same litters were offered a normal or a fat-enriched diet for 4 weeks between 140 and 169 days of age and were then slaughtered. Amoxicillin treatment transiently modified both mother and offspring microbiota. This was associated with early but transient reduction in ileal alkaline phosphatase, HSP70 (but not HSP27) and crypt depth, suggesting a milder or delayed intestinal response to bacteria in offspring born to antibiotic-treated mothers. More importantly, we disclosed long-term consequences of this treatment on jejunal alkaline phosphatase (reduced) and jejunal and ileal dipeptidylpeptidase IV (increased and decreased, respectively) of offspring born to antibiotic-treated dams. Significant interactions between early antibiotic treatment and later diet were observed for jejunal alkaline phosphatase and sucrase. By contrast, inducible HSPs were not affected. In conclusion, our data suggest that early changes in bacterial colonization not only modulate intestinal architecture and function transiently, but also exert site- and sometimes diet-specific long-term effects on key components of intestinal homeostasis.