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1.
Dis Model Mech ; 15(3)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35344037

RESUMO

Whole-body health relies on complex inter-organ signalling networks that enable organisms to adapt to environmental perturbations and to changes in tissue homeostasis. The intestine plays a major role as a signalling centre by producing local and systemic signals that are relayed to the body and that maintain intestinal and organismal homeostasis. Consequently, disruption of intestinal homeostasis and signalling are associated with systemic diseases and multi-organ dysfunction. In recent years, the fruit fly Drosophila melanogaster has emerged as a prime model organism to study tissue-intrinsic and systemic signalling networks of the adult intestine due to its genetic tractability and functional conservation with mammals. In this Review, we highlight Drosophila research that has contributed to our understanding of how the adult intestine interacts with its microenvironment and with distant organs. We discuss the implications of these findings for understanding intestinal and whole-body pathophysiology, and how future Drosophila studies might advance our knowledge of the complex interplay between the intestine and the rest of the body in health and disease.


Assuntos
Drosophila melanogaster , Drosophila , Animais , Drosophila melanogaster/genética , Homeostase , Intestinos/fisiologia , Mamíferos , Transdução de Sinais/genética
2.
Nutrients ; 14(3)2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35276796

RESUMO

Since many nutrients, including the three major ones of glucose, dipeptides, and cholesterol, are mainly absorbed in the small intestine, the assessment of their effects on intestinal tissue is important for the study of food absorption. However, cultured intestinal cell lines, such as Caco-2 cells, or animal models, which differ from normal human physiological conditions, are generally used for the evaluation of intestinal absorption and digestion. Therefore, it is necessary to develop an alternative in vitro method for more accurate analyses. In this study, we demonstrate inhibitory effects on nutrient absorption through nutrient transporters using three-dimensional xenogeneic-free human intestinal organoids (XF-HIOs), with characteristics of the human intestine, as we previously reported. We first show that the organoids absorbed glucose, dipeptide, and cholesterol in a transporter-dependent manner. Next, we examine the inhibitory effect of natural ingredients on the absorption of glucose and cholesterol. We reveal that glucose absorption was suppressed by epicatechin gallate or nobiletin, normally found in green tea catechin or citrus fruits, respectively. In comparison, cholesterol absorption was not inhibited by luteolin and quercetin, contained in some vegetables. Our findings highlight the usefulness of screening for the absorption of functional food substances using XF-HIOs.


Assuntos
Absorção Intestinal , Organoides , Animais , Células CACO-2 , Humanos , Intestinos/fisiologia , Nutrientes
3.
Sci Rep ; 12(1): 2018, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35132112

RESUMO

Zebrafish larval gut could be considered as an excellent model to study functions of vertebrate digestive organs, by virtue of its simplicity and transparency as well as the availability of mutants. However, there has been scant investigation of the detailed behavior of muscular and enteric nervous systems to convey bolus, an aggregate of digested food. Here we visualized peristalsis using transgenic lines expressing a genetically encoded Ca2+ sensor in the circular smooth muscles. An intermittent Ca2+ signal cycle was observed at the oral side of the bolus, with Ca2+ waves descending and ascending from there. We also identified a regular cycle of weaker movement that occurs regardless of the presence or absence of bolus, corresponding likely to slow waves. Direct photo-stimulation of circular smooth muscles expressing ChR2 could cause local constriction of the gut, while the stimulation of a single or a few neurons could cause the local induction or arrest of gut movements. These results indicate that the larval gut of zebrafish has basic features found in adult mammals despite the small number of enteric neurons, providing a foundation for the study, at the single-cell level in vivo, in controlling the gut behaviors in vertebrates.


Assuntos
Sinalização do Cálcio/fisiologia , Cálcio/metabolismo , Intestinos/fisiologia , Larva , Músculo Liso/fisiologia , Peristaltismo/fisiologia , Peixe-Zebra , Animais , Animais Geneticamente Modificados , Intestinos/inervação , Modelos Animais , Contração Muscular , Músculo Liso/metabolismo , Neurônios/fisiologia , Estimulação Luminosa
4.
Trends Cancer ; 8(5): 416-425, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35153158

RESUMO

The relationship between intestinal stem cells (ISCs) and colorectal cancer (CRC) has been a topic of intense study. Uncovering stem cell dynamics in homeostasis and following acquisition of oncogenic mutations has provided unprecedented insights into CRC initiation, and it is increasingly evident that the microenvironment plays a key role in regulating stem cell fate and functionality. Consequently, imbalances in the signaling between the niche and ISCs perturb homeostasis and promote cancer development. Furthermore, stem cell-like cells drive growth and progression of established CRCs and these cells also critically rely on microenvironmental input. Here, we highlight the importance of stem cell/niche interactions in developing and established CRC and discuss how these can be modulated to develop novel preventive and therapeutic interventions.


Assuntos
Neoplasias , Células-Tronco , Homeostase/fisiologia , Humanos , Intestinos/fisiologia , Neoplasias/genética , Nicho de Células-Tronco , Microambiente Tumoral/genética
5.
Gen Comp Endocrinol ; 318: 113986, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35114197

RESUMO

Guanylin (GN) stimulates Cl- secretion into the intestinal lumen of seawater-acclimated eels, but the molecular mechanisms of transepithelial Cl- transport are still unknown. In Ussing chamber experiments, we confirmed that mucosal application of eel GN reversed intestinal serosa-negative potential difference, indicating Cl- secretion. Serosal application of DNDS or mucosal application of DPC inhibited the GN effect, but serosal application of bumetanide had no effect. Removal of HCO3- from the serosal fluid also inhibited the GN effect. In intestinal sac experiments, mucosal GN stimulated luminal secretion of both Cl- and Na+, which was blocked by serosal DNDS. These results suggest that Cl- is taken up at the serosal side by DNDS-sensitive anion exchanger (AE) coupled with Na+-HCO3- cotransporter (NBC) but not by Na+-K+-2Cl- cotransporter 1 (NKCC1), and Cl- is secreted by unknown DPC-sensitive Cl- channel (ClC) at the mucosal side. The transcriptomic analysis combined with qPCR showed low expression of NKCC1 gene and no upregulation of the gene after seawater transfer, while high expression of ClC2 gene and upregulation after seawater transfer. In addition, SO42- transporters (apical Slc26a3/6 and basolateral Slc26a1) are also candidates for transcellular Cl- secretion in exchange of luminal SO42. Na+ secretion could occur through a paracellular route, as Na+-leaky claudin15 was highly expressed and upregulated after seawater transfer. High local Na+ concentration in the lateral interspace produced by Na+/K+-ATPase (NKA) coupled with K+ channels (Kir5.1b) seems to facilitate the paracellular transport. In situ hybridization confirmed the expression of the candidate genes in the epithelial enterocytes. Together with our previous results, we suggest that GN stimulates basolateral NBCela/AE2 and apical ClC2 to increase transcellular Cl- secretion in seawater eel intestine, which differs from the involvement of apical CFTR and basolateral NKCC1 as suggested in mammals and other teleosts.


Assuntos
Enguias , Peptídeos Natriuréticos , Animais , Cloretos , Enguias/metabolismo , Hormônios Gastrointestinais , Intestinos/fisiologia , Mamíferos/metabolismo , Peptídeos Natriuréticos/metabolismo , Água do Mar
6.
Elife ; 112022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34994689

RESUMO

Microsporidia are ubiquitous obligate intracellular pathogens of animals. These parasites often infect hosts through an oral route, but little is known about the function of host intestinal proteins that facilitate microsporidia invasion. To identify such factors necessary for infection by Nematocida parisii, a natural microsporidian pathogen of Caenorhabditis elegans, we performed a forward genetic screen to identify mutant animals that have a Fitness Advantage with Nematocida (Fawn). We isolated four fawn mutants that are resistant to Nematocida infection and contain mutations in T14E8.4, which we renamed aaim-1 (Antibacterial and Aids invasion by Microsporidia). Expression of AAIM-1 in the intestine of aaim-1 animals restores N. parisii infectivity and this rescue of infectivity is dependent upon AAIM-1 secretion. N. parisii spores in aaim-1 animals are improperly oriented in the intestinal lumen, leading to reduced levels of parasite invasion. Conversely, aaim-1 mutants display both increased colonization and susceptibility to the bacterial pathogen Pseudomonas aeruginosa and overexpression ofaaim-1 reduces P. aeruginosa colonization. Competitive fitness assays show that aaim-1 mutants are favored in the presence of N. parisii but disadvantaged on P. aeruginosa compared to wild-type animals. Together, this work demonstrates how microsporidia exploits a secreted protein to promote host invasion. Our results also suggest evolutionary trade-offs may exist to optimizing host defense against multiple classes of pathogens.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/parasitologia , Interações Hospedeiro-Patógeno , Microsporídios/fisiologia , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Intestinos/fisiologia
7.
Nutrients ; 14(2)2022 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-35057558

RESUMO

The disturbance of intestinal microorganisms and the exacerbation of type 2 diabetes (T2D) are mutually influenced. In this study, the effect of exopolysaccharides (EPS) from Lactobacillus plantarum JY039 on the adhesion of Lactobacillus paracasei JY062 was investigated, as well as their preventive efficacy against T2D. The results showed that the EPS isolated from L. plantarum JY039 effectively improved the adhesion rate of L. paracasei JY062 to Caco-2 cells (1.8 times) and promoted the proliferation of L. paracasei JY062. In the mice experiment, EPS, L. paracasei JY062 and their complex altered the structure of the intestinal microbiota, which elevated the proportion of Bifidobacterium, Faecalibaculum, while inversely decreasing the proportion of Firmicutes, Muribaculaceae, Lachnospiraceae and other bacteria involved in energy metabolism (p < 0.01; p < 0.05); enhanced the intestinal barrier function; promoted secretion of the gut hormone peptide YY (PYY) and glucagon-like peptide-1 (GLP-1); and reduced inflammation by balancing pro-inflammatory factors IL-6, TNF-α and anti-inflammatory factor IL-10 (p < 0.01; p < 0.05). These results illustrate that EPS and L. paracasei JY062 have the synbiotic potential to prevent and alleviate T2D.


Assuntos
Aderência Bacteriana/efeitos dos fármacos , Diabetes Mellitus Tipo 2/prevenção & controle , Lactobacillus paracasei/fisiologia , Lactobacillus plantarum/química , Polissacarídeos Bacterianos/farmacologia , Simbióticos , Animais , Aderência Bacteriana/fisiologia , Glicemia/metabolismo , Células CACO-2 , Metabolismo Energético , Microbioma Gastrointestinal/fisiologia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Inflamação/prevenção & controle , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Intestinos/microbiologia , Intestinos/fisiologia , Lactobacillus paracasei/crescimento & desenvolvimento , Fígado/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pâncreas/fisiologia , Peptídeo YY/metabolismo , Distribuição Aleatória , Fator de Necrose Tumoral alfa/metabolismo
8.
J Immunol Res ; 2022: 2316368, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35071607

RESUMO

High concentration oxygen is widely used in the treatment of neonates, which has a significant effect on improving blood oxygen concentration in neonates with respiratory distress. The adverse effects of hyperoxia therapy on the lung, retina, and neurodevelopment of newborns have been extensively studied, but less attention has been paid to intestinal damage caused by hyperoxia therapy. In this review, we focus on the physical, immune, and microorganism barriers of the intestinal tract and discuss neonatal intestinal tract damage caused by hyperoxia therapy and analyze the molecular mechanism of intestinal damage caused by hyperoxia in combination with necrotizing enterocolitis.


Assuntos
Intestinos/fisiologia , Animais , Animais Recém-Nascidos , Humanos , Hiperóxia , Recém-Nascido , Mucosa Intestinal , Pulmão
9.
Dev Comp Immunol ; 128: 104314, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34785271

RESUMO

Nicotinamide phosphoribosyltransferase (Nampt) can act extracellularly as a mediator of inflammation or intracellularly as a rate-limiting enzyme, regulating nicotinamide adenine dinucleotide (NAD) biosynthesis in the NAD salvage pathway. Nampt exerts important immunological functions during infection in mammals. However, the in vivo function of fish Nampt in immune regulation and inflammation is essentially unknown. With an aim to elucidate the antimicrobial mechanism of Nampt in fish, we in this study examined the function of Nampt from hybrid crucian carp. Hybrid crucian carp Nampt (WR-Nampt) possesses the conserved nicotinamide phosphoribosyltransferase domain and shows high similarity to that of mammalian Nampt. WR-Nampt is expressed in multiple tissues and is upregulated by bacterial infection. Overexpression of WR-Nampt significantly increased the number of goblet cells of distal intestine. In addition, WR-Nampt induced significant inductions in the expression of the antimicrobial molecules (IL-22, Hepcidin-1, LEAP-2 and MUC2) and tight junctions (ZO-1 and Occludin). Consistent with this, fish administered with WR-Nampt significantly alleviated the intestinal permeability and apoptosis, thereby enhancing host's resistance against bacterial infection. Together these results revealed the potential effect of WR-Nampt in intestinal barrier and immune defense against bacterial infection.


Assuntos
Infecções Bacterianas , Carpas , Intestinos , Animais , Infecções Bacterianas/imunologia , Carpas/metabolismo , Citocinas/metabolismo , Imunidade Inata , Inflamação , Intestinos/metabolismo , Intestinos/fisiologia , Mamíferos , Nicotinamida Fosforribosiltransferase/genética , Nicotinamida Fosforribosiltransferase/metabolismo
11.
Mucosal Immunol ; 15(1): 109-119, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34433904

RESUMO

T and B cells employ integrin α4ß7 to migrate to intestine under homeostatic conditions. Whether those cells differentially rely on α4ß7 for homing during inflammatory conditions has not been fully examined. This may have implications for our understanding of the mode of action of anti-integrin therapies in inflammatory bowel disease (IBD). Here, we examined the role of α4ß7 integrin during chronic colitis using IL-10-/- mice, ß7-deficient IL-10-/-, IgA-deficient IL-10-/- mice, and antibody blockade of MAdCAM-1. We found that α4ß7 was predominantly expressed by B cells. ß7 deficiency and MAdCAM-1 blockade specifically depleted antibody secreting cells (ASC) (not T cells) from the colonic LP, leading to a fecal pan-immunoglobulin deficit, severe colitis, and alterations of microbiota composition. Colitis was not due to defective regulation, as dendritic cells (DC), regulatory T cells, retinaldehyde dehydrogenase (RALDH) expression, activity, and regulatory T/B-cell cytokines were all comparable between the strains/treatment. Finally, an IgA deficit closely recapitulated the clinical phenotype and altered microbiota composition of ß7-deficient IL-10-/- mice. Thus, a luminal IgA deficit contributes to accelerated colitis in the ß7-deficient state. Given the critical/nonredundant dependence of IgA ASC on α4ß7:MAdCAM-1 for intestinal homing, B cells may represent unappreciated targets of anti-integrin therapies.


Assuntos
Células Produtoras de Anticorpos/imunologia , Moléculas de Adesão Celular/metabolismo , Colite/imunologia , Microbioma Gastrointestinal/imunologia , Doenças Inflamatórias Intestinais/imunologia , Integrina alfa4/metabolismo , Cadeias beta de Integrinas/metabolismo , Intestinos/fisiologia , Mucoproteínas/metabolismo , Animais , Doença Crônica , Modelos Animais de Doenças , Humanos , Imunoglobulina A/metabolismo , Imunomodulação , Cadeias beta de Integrinas/genética , Interleucina-10/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
12.
Endocrinology ; 163(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34534278

RESUMO

Cross-talk between peripheral tissues is essential to ensure the coordination of nutrient intake with disposition during the feeding period, thereby preventing metabolic disease. This mini-review considers the interactions between the key peripheral tissues that constitute the metabolic clock, each of which is considered in a separate mini-review in this collation of articles published in Endocrinology in 2020 and 2021, by Martchenko et al (Circadian rhythms and the gastrointestinal tract: relationship to metabolism and gut hormones); Alvarez et al (The microbiome as a circadian coordinator of metabolism); Seshadri and Doucette (Circadian regulation of the pancreatic beta cell); McCommis et al (The importance of keeping time in the liver); Oosterman et al (The circadian clock, shift work, and tissue-specific insulin resistance); and Heyde et al (Contributions of white and brown adipose tissues to the circadian regulation of energy metabolism). The use of positive- and negative-feedback signals, both hormonal and metabolic, between these tissues ensures that peripheral metabolic pathways are synchronized with the timing of food intake, thus optimizing nutrient disposition and preventing metabolic disease. Collectively, these articles highlight the critical role played by the circadian clock in maintaining metabolic homeostasis.


Assuntos
Relógios Circadianos/fisiologia , Ritmo Circadiano , Comportamento Alimentar , Homeostase , Fígado/fisiologia , Adipócitos/citologia , Animais , Endocrinologia/métodos , Ingestão de Energia , Metabolismo Energético/fisiologia , Retroalimentação Fisiológica , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Intestinos/fisiologia , Ilhotas Pancreáticas/citologia , Mamíferos/fisiologia , Doenças Metabólicas/metabolismo , Microbiota , Modelos Biológicos , Células Musculares/citologia , Músculo Esquelético/fisiologia
13.
Fish Shellfish Immunol ; 120: 706-715, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34954371

RESUMO

The present study was conducted to investigate the effects of yeast culture on the growth, health and microflora of the juvenile largemouth bass fed high-starch diet. The experiment set three isonitrogenous and isolipidic diets, control (high-starch diet), HSY1 (high-starch diet with 1% yeast culture) and HSY3 (high-starch diet with 3% yeast culture). A feeding trial was conducted in largemouth bass juveniles for 8 weeks. The results indicated fish fed with 3% yeast culture not only could improve specific growth rate (SGR), but also significantly decreased hepatic lipid content, hepatic glycogen content, and hepatopancreas somatic index (HSI) compared with the control group (p<0.05). The total superoxide dismutase (T-SOD) and catalase (CAT) activities of HSY3 group significantly increased while malondialdehyde (MDA) content significantly reduced in liver compared with the control group (p<0.05). Meanwhile, the mRNA expression levels of hepatic Sod and Cat were up-regulated (p<0.05), and liver metabolism showed 111 metabolites were significantly changed in HSY3 group, liver lipid metabolism pathway remarkably changed. Besides, the intestinal anti-inflammatory cytokines were significantly up-regulated, and the pro-inflammatory cytokines were significantly down-regulated as the inclusion of yeast culture (p<0.05). Notably, HSY3 group diet up-regulated the expression of Zo-1, Claudin and Occludin in intestine compared with the other groups (p<0.05). Serum d-lactate (D-lac), diamine oxidase (DAO) and lipopolysaccharide (LPS) decreased significantly with the inclusion of yeast culture (p<0.05). Furthermore, the abundance of probiotics (such as Lactobacillus, Bacillus and Bifidobacterium) increased significantly, and the abundance of intestinal potential pathogenic bacteria (Plesiomonas) decreased in HSY3 group (p<0.05). The phenotypic analysis showed that gram-negative bacteria significantly decreased while gram-positive bacteria increased in HSY3 group (p<0.05). All in all, this study revealed that supplementation of 3% yeast culture can improve the growth performance and the health of juvenile largemouth bass, and has the potential to be used as an effective synbiotics for M. salmoides.


Assuntos
Bass , Dieta , Microbiota , Saccharomyces cerevisiae , Amido/administração & dosagem , Ração Animal/análise , Animais , Antioxidantes , Bass/imunologia , Bass/microbiologia , Catalase , Citocinas , Dieta/veterinária , Intestinos/fisiologia , Fígado/fisiologia , Superóxido Dismutase
14.
Artigo em Inglês | MEDLINE | ID: mdl-34543726

RESUMO

Animals which feed infrequently and on large prey, like many snake species, are characterized by a high magnitude of gut upregulation upon ingesting a meal. The intensity of intestinal upregulation was hypothesized to be proportional to the time and energy required for food processing (Specific-Dynamic-Action; SDA); hence, a positive correlation between the scope of intestinal growth and SDA response can be deduced. Such a correlation would support the so far not well established link between the intestinal and metabolic consequences of digestion. In this study I tested this prediction using an interspecific dataset on snakes gleaned from published sources. I found that SDAduration and SDAscope were positively correlated with post-feeding factorial increase in small intestine mass, but not with microvillar elongation. This indicates that a wide range of whole intestine remodelling (up- but potentially also downregulation) may temporarily prolong meal processing and that a greater magnitude of intestinal growth requires a stronger metabolic elevation. However, these effects do not seem large enough to drive the variation in the entire energetic costs of digestion, because SDAexpenditure was not affected either by intestinal or microvillar growth. I therefore propose that intestinal upregulation elicits non-negligible costs, but that these costs are a fairly small component of the whole SDAexpenditure.


Assuntos
Digestão/fisiologia , Serpentes/fisiologia , Animais , Metabolismo Energético , Comportamento Alimentar/fisiologia , Intestinos/anatomia & histologia , Intestinos/crescimento & desenvolvimento , Intestinos/fisiologia , Modelos Biológicos , Consumo de Oxigênio , Período Pós-Prandial/fisiologia , Comportamento Predatório/fisiologia , Serpentes/anatomia & histologia , Serpentes/crescimento & desenvolvimento , Regulação para Cima
15.
Food Funct ; 13(2): 514-529, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-34935814

RESUMO

Intestinal inflammation represented by inflammatory bowel disease (IBD) has become a global epidemic disease and the number of patients with IBD continues to increase. This digestive tract disease not only affects the absorption of food components by destroying the intestinal epithelial structure, but also can induce diseases in remote organs via the gut-organ axis, seriously harming human health. Nowadays, increasing attention is being paid to the nutritional and medicinal value of food components with increasing awareness among the general public regarding health. As an important member of the isothiocyanates, sulforaphane (SFN) is abundant in cruciferous plants and is famous for its excellent anti-cancer effects. With the development of clinical research, more physiological activities of SFN, such as antidepressant, hypoglycemic and anti-inflammatory activities, have been discovered, supporting the fact that SFN and SFN-rich sources have great potential to be dietary supplements that are beneficial to health. This review summarizes the characteristics of intestinal inflammation, the anti-inflammatory mechanism of SFN and its various protective effects on intestinal inflammation, and the possible future applications of SFN for promoting intestinal health have also been discussed.


Assuntos
Anti-Inflamatórios , Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Isotiocianatos , Sulfóxidos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Brassicaceae , Colite/metabolismo , Colite/microbiologia , Colite/fisiopatologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Intestinos/efeitos dos fármacos , Intestinos/fisiologia , Isotiocianatos/química , Isotiocianatos/metabolismo , Isotiocianatos/farmacologia , Camundongos , Sulfóxidos/química , Sulfóxidos/metabolismo , Sulfóxidos/farmacologia , Verduras
16.
Cell Mol Life Sci ; 79(1): 1, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34910257

RESUMO

Intestinal mesenchymal cells encompass multiple subsets, whose origins, functions, and pathophysiological importance are still not clear. Here, we used the Col6a1Cre mouse, which targets distinct fibroblast subsets and perivascular cells that can be further distinguished by the combination of the CD201, PDGFRα and αSMA markers. Developmental studies revealed that the Col6a1Cre mouse also targets mesenchymal aggregates that are crucial for intestinal morphogenesis and patterning, suggesting an ontogenic relationship between them and homeostatic PDGFRαhi telocytes. Cell depletion experiments in adulthood showed that Col6a1+/CD201+ mesenchymal cells regulate homeostatic enteroendocrine cell differentiation and epithelial proliferation. During acute colitis, they expressed an inflammatory and extracellular matrix remodelling gene signature, but they also retained their properties and topology. Notably, both in homeostasis and tissue regeneration, they were dispensable for normal organ architecture, while CD34+ mesenchymal cells expanded, localised at the top of the crypts, and showed increased expression of villous-associated morphogenetic factors, providing thus evidence for the plasticity potential of intestinal mesenchymal cells. Our results provide a comprehensive analysis of the identities, origin, and functional significance of distinct mesenchymal populations in the intestine.


Assuntos
Colágeno Tipo VI/metabolismo , Receptor de Proteína C Endotelial/metabolismo , Intestinos/metabolismo , Animais , Diferenciação Celular , Linhagem da Célula , Plasticidade Celular , Proliferação de Células , Colite/induzido quimicamente , Colite/patologia , Colágeno Tipo VI/deficiência , Colágeno Tipo VI/genética , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Intestinos/citologia , Intestinos/fisiologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Knockout , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Regeneração
17.
Int J Mol Sci ; 22(24)2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34948271

RESUMO

Over the past years, several preclinical in vitro and ex vivo models have been developed that helped to understand some of the critical aspects of intestinal functions in health and disease such as inflammatory bowel disease (IBD). However, the translation to the human in vivo situation remains problematic. The main reason for this is that these approaches fail to fully reflect the multifactorial and complex in vivo environment (e.g., including microbiota, nutrition, and immune response) in the gut system. Although conventional models such as cell lines, Ussing chamber, and the everted sac are still used, increasingly more sophisticated intestinal models have been developed over the past years including organoids, InTESTine™ and microfluidic gut-on-chip. In this review, we gathered the most recent insights on the setup, advantages, limitations, and future perspectives of most frequently used in vitro and ex vivo models to study intestinal physiology and functions in health and disease.


Assuntos
Mucosa Intestinal/metabolismo , Mucosa Intestinal/fisiologia , Modelos Biológicos , Linhagem Celular , Microbioma Gastrointestinal/fisiologia , Humanos , Intestinos/fisiologia , Organoides
18.
Nutrients ; 13(12)2021 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-34960094

RESUMO

Healthy, plant-based diets, rich in fermentable residues, may induce gas-related symptoms. The aim of this exploratory study was to assess the effects of a fermented milk product, containing probiotics, on the tolerance of a healthy diet in patients with disorders of gut-brain interactions (DGBI), complaining of excessive flatulence. In an open design, a 3-day healthy, mostly plant-based diet was administered to patients with DGBI (52 included, 43 completed) before and at the end of 28 days of consumption of a fermented milk product (FMP) containing Bifidobacterium animalis subsp. lactis CNCM I-2494 and lactic acid bacteria. As compared to a habitual diet, the flatulogenic diet increased the perception of digestive symptoms (flatulence score 7.1 ± 1.6 vs. 5.8 ± 1.9; p < 0.05) and the daily number of anal gas evacuations (22.4 ± 12.5 vs. 16.5 ± 10.2; p < 0.0001). FMP consumption reduced the flatulence sensation score (by -1.6 ± 2.2; p < 0.05) and the daily number of anal gas evacuations (by -5.3 ± 8.2; p < 0.0001). FMP consumption did not significantly alter the overall gut microbiota composition, but some changes in the microbiota correlated with the observed clinical improvement. The consumption of a product containing B. lactis CNCM I-2494 improved the tolerance of a healthy diet in patients with DGBI, and this effect may be mediated, in part, by the metabolic activity of the microbiota.


Assuntos
Bifidobacterium animalis , Produtos Fermentados do Leite/microbiologia , Dieta Saudável/efeitos adversos , Dieta Vegetariana/efeitos adversos , Flatulência/etiologia , Flatulência/prevenção & controle , Gases , Intestinos/fisiologia , Adulto , Idoso , Bifidobacterium animalis/fisiologia , Feminino , Flatulência/microbiologia , Microbioma Gastrointestinal , Humanos , Masculino , Pessoa de Meia-Idade
19.
Cell Rep ; 37(7): 110006, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34788614

RESUMO

Secretory immunoglobulin A (SIgA) can travel to and from the lumen and transport antigen to subepithelial cells. However, IgM can also multimerize into functional secretory component-bound immunoglobulin. While it is already known that both SIgA and SIgM undergo transcytosis to be secreted at the mucosal surface, only SIgA has been shown to perform retrotranscytosis through microfold cells (M cells) of the Peyer's patch. Here, we investigate whether SIgM could also be taken up by M cells via retrotranscytosis. This transport involves FcµR binding at the apical membrane of M cells. We then demonstrate that SIgM can be exploited by SIgM-p24 (HIV-capsid protein) complexes during immunization in the nasal- or gut-associated lymphoid tissue (NALT or GALT), conferring efficient immune responses against p24. Our data demonstrate a mucosal function of SIgM, which could play a role in the regulation of mucosal immunity.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Intestinos/fisiologia , Proteínas de Membrana/metabolismo , Transcitose/fisiologia , Animais , Proteínas Reguladoras de Apoptose/fisiologia , Feminino , Imunidade nas Mucosas/fisiologia , Imunoglobulina A Secretora/metabolismo , Imunoglobulina M/imunologia , Mucosa Intestinal/metabolismo , Intestinos/imunologia , Intestinos/metabolismo , Proteínas de Membrana/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Nódulos Linfáticos Agregados/citologia , Transcitose/genética
20.
Front Immunol ; 12: 717392, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790192

RESUMO

Diet and gut microbial metabolites mediate host immune responses and are central to the maintenance of intestinal health. The metabolite-sensing G-protein coupled receptors (GPCRs) bind metabolites and trigger signals that are important for the host cell function, survival, proliferation and expansion. On the contrary, inadequate signaling of these metabolite-sensing GPCRs most likely participate to the development of diseases including inflammatory bowel diseases (IBD). In the intestine, metabolite-sensing GPCRs are highly expressed by epithelial cells and by specific subsets of immune cells. Such receptors provide an important link between immune system, gut microbiota and metabolic system. Member of these receptors, GPR35, a class A rhodopsin-like GPCR, has been shown to be activated by the metabolites tryptophan-derived kynurenic acid (KYNA), the chemokine CXCL17 and phospholipid derivate lysophosphatidic acid (LPA) species. There have been studies on GPR35 in the context of intestinal diseases since its identification as a risk gene for IBD. In this review, we discuss the pharmacology of GPR35 including its proposed endogenous and synthetic ligands as well as its antagonists. We elaborate on the risk variants of GPR35 implicated in gut-related diseases and the mechanisms by which GPR35 contribute to intestinal homeostasis.


Assuntos
Homeostase , Doenças Inflamatórias Intestinais/patologia , Intestinos/fisiologia , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Animais , Quimiocinas CXC/metabolismo , Humanos , Ácido Cinurênico/metabolismo , Lisofosfolipídeos/metabolismo
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