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1.
Mol Nutr Food Res ; 68(6): e2300458, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38389157

RESUMO

SCOPE: Processing of whey protein concentrate (WPC) for infant formulas may induce protein modifications with severe consequences for preterm newborn development. The study investigates how conventional WPC and a gently processed skim milk-derived WPC (SPC) affect gut and immune development after birth. METHODS AND RESULTS: Newborn, preterm pigs used as a model of preterm infants were fed formula containing WPC, SPC, extra heat-treated SPC (HT-SPC), or stored HT-SPC (HTS-SPC) for 5 days. SPC contained no protein aggregates and more native lactoferrin, and despite higher Maillard reaction product (MRP) formation, the clinical response and most gut and immune parameters are similar to WPC pigs. SPC feeding negatively impacts intestinal MRP accumulation, mucosa, and bacterial diversity. In contrast, circulating T-cells are decreased and oxidative stress- and inflammation-related genes are upregulated in WPC pigs. Protein aggregation and MRP formation increase in HTS-SPC, leading to reduced antibacterial activity, lactase/maltase ratio, circulating neutrophils, and cytotoxic T-cells besides increased gut MRP accumulation and expression of TNFAIP3. CONCLUSION: The gently processed SPC has more native protein, but higher MRP levels than WPC, resulting in similar tolerability but subclinical adverse gut effects in preterm pigs. Additional heat treatment and storage further induce MRP formation, gut inflammation, and intestinal mucosal damage.


Assuntos
Fórmulas Infantis , Leite , Humanos , Recém-Nascido , Lactente , Animais , Suínos , Proteínas do Soro do Leite , Intestinos/fisiologia , Recém-Nascido Prematuro , Inflamação
2.
Int Immunopharmacol ; 130: 111675, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38377852

RESUMO

The aim of our research was to investigate the effects of Bacillus amyloliquefaciens SC06 on growth performance, immune status, intestinal stem cells (ISC) proliferation and differentiation, and gut microbiota in weaned piglets. Twelve piglets (male, 21 days old, 6.11 ± 0.12 kg) were randomly allocated to CON and SC06 (1 × 108 cfu/kg to diet) groups. This experiment lasted three weeks. Our results showed that SC06 increased (P < 0.05) growth performance and reduced the diarrhea rate in weaned piglets. In addition, SC06 increased intestinal morphology and interleukin (IL)-10 levels, and decreased (P < 0.01) necrosis factor (TNF-α) levels in jejunum and serum. Moreover, weaning piglets fed SC06 had a better balance of colonic microbiota, with an increase in the abundance of Lactobacillus. Furthermore, SC06 enhanced ISCs proliferation and induced its differentiation to goblet cells via activating wnt/ß-catenin pathway in weaned piglets and intestinal organoid. Taken together, SC06 supplementation improved the growth performance and decreased inflammatory response of piglets by modulating intestinal microbiota, thereby accelerating ISC proliferation and differentiation and promoting epithelial barrier healing.


Assuntos
Bacillus amyloliquefaciens , Microbioma Gastrointestinal , Animais , Masculino , Proliferação de Células , Suplementos Nutricionais/análise , Intestinos/fisiologia , Suínos , Desmame
3.
Am J Physiol Gastrointest Liver Physiol ; 326(5): G504-G524, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38349111

RESUMO

Genotoxic agents such as doxorubicin (DXR) can cause damage to the intestines that can be ameliorated by fasting. How fasting is protective and the optimal timing of fasting and refeeding remain unclear. Here, our analysis of fasting/refeeding-induced global intestinal transcriptional changes revealed metabolic shifts and implicated the cellular energetic hub mechanistic target of rapamycin complex 1 (mTORC1) in protecting from DXR-induced DNA damage. Our analysis of specific transcripts and proteins in intestinal tissue and tissue extracts showed that fasting followed by refeeding at the time of DXR administration reduced damage and caused a spike in mTORC1 activity. However, continued fasting after DXR prevented the mTORC1 spike and damage reduction. Surprisingly, the mTORC1 inhibitor, rapamycin, did not block fasting/refeeding-induced reduction in DNA damage, suggesting that increased mTORC1 is dispensable for protection against the initial DNA damage response. In Ddit4-/- mice [DDIT4 (DNA-damage-inducible transcript 4) functions to regulate mTORC1 activity], fasting reduced DNA damage and increased intestinal crypt viability vs. ad libitum-fed Ddit4-/- mice. Fasted/refed Ddit4-/- mice maintained body weight, with increased crypt proliferation by 5 days post-DXR, whereas ad libitum-fed Ddit4-/- mice continued to lose weight and displayed limited crypt proliferation. Genes encoding epithelial stem cell and DNA repair proteins were elevated in DXR-injured, fasted vs. ad libitum Ddit4-/- intestines. Thus, fasting strongly reduced intestinal damage when normal dynamic regulation of mTORC1 was lost. Overall, the results confirm that fasting protects the intestines against DXR and suggests that fasting works by pleiotropic - including both mTORC1-dependent and independent - mechanisms across the temporally dynamic injury response.NEW & NOTEWORTHY New findings are 1) DNA damage reduction following a 24-h fast depends on the timing of postfast refeeding in relation to chemotherapy initiation; 2) fasting/refeeding-induced upregulation of mTORC1 activity is not required for early (6 h) protection against DXR-induced DNA damage; and 3) fasting increases expression of intestinal stem cell and DNA damage repair genes, even when mTORC1 is dysregulated, highlighting fasting's crucial role in regulating mTORC1-dependent and independent mechanisms in the dynamic recovery process.


Assuntos
Doxorrubicina , Intestino Delgado , Intestinos , Camundongos , Animais , Intestinos/fisiologia , Alvo Mecanístico do Complexo 1 de Rapamicina , Adutos de DNA , Jejum/fisiologia
4.
Sci Rep ; 14(1): 825, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191903

RESUMO

In vitro simulators of the human gastrointestinal (GI) tract are remarkable technological platforms for studying the impact of food on the gut microbiota, enabling continuous and real-time monitoring of key biomarkers. However, comprehensive real-time monitoring of gaseous biomarkers in these systems is required with a cost-effective approach, which has been challenging to perform experimentally to date. In this work, we demonstrate the integration and in-line use of carbon nanotube (CNT)-based chemiresitive gas sensors coated with a thin polydimethylsiloxane (PDMS) membrane for the continuous monitoring of gases within the Simulator of the Human Microbial Ecosystem (SHIME). The findings demonstrate the ability of the gas sensor to continuously monitor the different phases of gas production in this harsh, anaerobic, highly humid, and acidic environment for a long exposure time (16 h) without saturation. This establishes our sensor platform as an effective tool for real-time monitoring of gaseous biomarkers in in vitro systems like SHIME.


Assuntos
Gases , Intestinos , Humanos , Biomarcadores , Alimentos , Nanotubos de Carbono , Intestinos/fisiologia
5.
Fish Shellfish Immunol ; 146: 109362, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38218423

RESUMO

A 56-d feeding trial was conducted to evaluate the influences of Rhodiola rosea L. on digestive enzyme activities, intestinal barrier, inflammatory response, and microbiota dysbiosis in Lateolabrax maculatus juveniles (9.37 ± 0.03 g) fed with high-carbohydrate diets. Six diets were designed: a control diet (20% corn starch, Control), high-carbohydrate diet (30% corn starch, HC1), and four high-carbohydrate diets supplemented with Rhodiola rosea L. at 30, 60, 90 and 120 mg/kg (HC2, HC3, HC4 and HC5, respectively). Compared with the control group, the HC1 diet remarkably increased α-amylase, lipase, and chymotrypsin activities in the intestine (p < 0.05), as well as the mRNA levels of Claudin-15, NF-κB, TNF-α, IL-1ß, and IL-8 (p < 0.05) and the relative abundance of Proteobacteria and Photobacterium in the intestine, which belong to the phylum and genus level, respectively. But the opposite trend was found in muscular thickness and villus lengths (p < 0.05), the mRNA levels of Occludin, ZO-1, and TGF-ß (p < 0.05), at the level of phylum and genus level in the HC1 group, and the relative abundance of Firmicutes, Bacteroidetes, and Bacillus in the intestine compared with the control group. Intestinal chymotrypsin activity was significantly higher in the HC3 group and intestinal muscular thickness and villus lengths were also significantly higher in the HC2, HC3, HC4, and HC5 groups compared to the HC1 group (p < 0.05). In addition, Occludin mRNA expression in the intestine was significantly increased in the HC2, HC4, and HC5 groups compared to the HC1 group. ZO-1 and TGF-ß mRNA expression in the intestine were significantly increased in the HC2, HC3, HC4, and HC5 groups compared to the HC1 group (p < 0.05). At the phylum level, the relative abundance of Firmicutes and Bacteroidetes was higher in the intestine in the HC2, HC3, HC4, and HC5 groups than that in the HC1 group. On the contrary, intestinal lipase and chymotrypsin activities were significantly decreased in the HC2 group compared to the HC1 group, respectively (p < 0.05). The Claudin-15, NF-κB, TNF-α, IL-1ß, and IL-8 mRNA expression in the intestine were significantly decreased in the HC2, HC3, HC4, and HC5 groups compared to the HC1 group (p < 0.05). Besides, at the genus level, compared to the HC1 group, the relative abundance of Photobacterium in the intestine and the diversity of the intestinal microbiota in the HC2, HC3, HC4, and HC5 groups were all decreased. In conclusion, these results demonstrated that the addition of Rhodiola rosea L. in high-carbohydrate diets can improve intestinal digestive enzyme activities, inflammatory response and intestinal barrier-related gene expression, and microbiota dysbiosis in L. maculatus. The suitable supplemental level of Rhodiola rosea L. in high-carbohydrate diets of L. maculatus is 60 mg/kg.


Assuntos
Microbiota , Rhodiola , Animais , NF-kappa B , Fator de Necrose Tumoral alfa , Quimotripsina , Disbiose , Interleucina-8 , Ocludina , Intestinos/fisiologia , Dieta/veterinária , Peixes , Lipase , RNA Mensageiro , Amido , Fator de Crescimento Transformador beta , Ração Animal/análise
6.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38280204

RESUMO

This study aimed to investigate the effects of xylanase on growth performance and intestinal health of nursery pigs fed diets with reduced metabolizable energy (ME). One hundred ninety-two pigs at 8.7 kg ±â€…0.7 body weight (BW) after 7 d of weaning were allotted in a randomized complete block design with initial BW and sex as blocks. Eight dietary treatments consisted of 5 ME levels (3,400, 3,375, 3,350, 3,325, and 3,300 kcal ME/kg) below the NRC (2012) requirement and 4 levels of xylanase (0, 1,200, 2,400, and 3,600 XU/kg) to a diet with 3,300 kcal ME/kg. All pigs received their respective treatments for 35 d in 2 phases, pre-starter (14 d) and starter (21 d). On day 35, eight pigs in 3,400 kcal/kg (CON), 3,300 kcal/kg (LE), and 3,300 kcal/kg + 3,600 XU xylanase/kg (LEX) were euthanized to collect jejunal tissues and digesta for the evaluation of mucosa-associated microbiota, intestinal immune response, oxidative stress status, intestinal morphology, crypt cell proliferation, and digesta viscosity as well as ileal digesta to measure apparent ileal digestibility. Data were analyzed using the MIXED procedure on SAS 9.4. The LE increased (P < 0.05) jejunal digesta viscosity, tended to have decreased (P = 0.053) relative abundance of Prevotella, and tended to increase (P = 0.055) Lactobacillus. The LE also increased (P < 0.05) the concentration of protein carbonyl whereas malondialdehyde, villus height (VH), villus height to crypt depth ratio (VH:CD), apparent ileal digestibility (AID) of nutrients, and finally average daily feed intake were decreased (P < 0.05). The LE did not affect average daily gain (ADG). The LEX decreased (P < 0.05) digesta viscosity, increased (P < 0.05) the relative abundance of Prevotella, decreased (P < 0.05) Helicobacter, decreased (P < 0.05) the concentration of protein carbonyl, tended to increase (P = 0.065) VH, and decreased (P < 0.05) VH:CD and crypt cell proliferation. Moreover, LEX increased (P < 0.05) the AID of dry matter and gross energy and tended to increase (P = 0.099; P = 0.076) AID of crude protein, and ether extract. The LEX did not affect ADG but did tend to decrease (P = 0.070) fecal score during the starter phase. Overall, reducing ME negatively affected intestinal health parameters and nutrient digestibility without affecting growth. Supplementation of xylanase mitigated some of the negative effects observed by ME reduction on intestinal health and digestibility of nutrients without affecting growth.


Dietary inclusion of fats in the feeds of nursery pigs allows nutritionists to increase the energy density of the feed. Some researchers believe the value of adding fat in nursery feeds goes beyond meeting the energy specification of the feed but rather as a supply of fatty acids that can regulate various bodily processes. Volatility in feedstuff prices has resulted in increased inclusion of coproducts rich in nonstarch polysaccharides (NSP) and a decrease in dietary fat in nursery pig diets in an effort to boost economic sustainability with minimal compromise of growth. Common feedstuffs of plant origin possess an inherent amount of NSP that can elicit negative effects on the digesta viscosity, intestinal microbiota, and digestibility of nutrients. Supplemental enzymes such as xylanase target specific NSP components within the feed to alleviate some of these negative effects and may release otherwise indigestible nutrients for absorption. The aim of this study was to investigate the impact of reducing metabolizable energy (ME) of the feed up to 100 kcal ME/kg on growth performance, intestinal health, immune status, and the composition of the mucosa-associated microbiota as well as the ability of xylanase to mediate the negative effects imposed by a reduction in supplemental fat to lower ME.


Assuntos
Suplementos Nutricionais , Digestão , Animais , Suínos , Endo-1,4-beta-Xilanases , Dieta/veterinária , Intestinos/fisiologia , Peso Corporal , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal
7.
Science ; 382(6670): 527-528, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37917691
8.
Int J Food Sci Nutr ; 74(7): 730-745, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37758199

RESUMO

Diet is a critical regulator for physiological metabolism and tissue homeostasis, with a close relation to health and disease. As an important organ for digestion and absorption, the intestine comes into direct contact with many dietary components. The rapid renewal of its mucosal epithelium depends on the continuous proliferation and differentiation of intestinal stem cells (ISCs). The function and metabolism of ISCs can be controlled by a variety of dietary patterns including calorie restriction, fasting, high-fat, ketogenic, and high-sugar diets, as well as different nutrients including vitamins, amino acids, dietary fibre, and probiotics. Therefore, dietary interventions targeting ISCs may make it possible to prevent and treat intestinal disorders such as colon cancer, inflammatory bowel disease, and radiation enteritis. This review summarised recent research on the role and mechanism of diet in regulating ISCs, and discussed the potential of dietary modulation for intestinal diseases.


Assuntos
Doenças Inflamatórias Intestinais , Intestinos , Humanos , Intestinos/fisiologia , Dieta , Células-Tronco/metabolismo , Fibras na Dieta/metabolismo , Mucosa Intestinal/metabolismo
9.
Dis Model Mech ; 16(4)2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-37144684

RESUMO

A major challenge in the biology of aging is to understand how specific age-onset pathologies relate to the overall health of the organism. The integrity of the intestinal epithelium is essential for the wellbeing of the organism throughout life. In recent years, intestinal barrier dysfunction has emerged as an evolutionarily conserved feature of aged organisms, as reported in worms, flies, fish, rodents and primates. Moreover, age-onset intestinal barrier dysfunction has been linked to microbial alterations, elevated immune responses, metabolic alterations, systemic health decline and mortality. Here, we provide an overview of these findings. We discuss early work in the Drosophila model that sets the stage for examining the relationship between intestinal barrier integrity and systemic aging, then delve into research in other organisms. An emerging concept, supported by studies in both Drosophila and mice, is that directly targeting intestinal barrier integrity is sufficient to promote longevity. A better understanding of the causes and consequences of age-onset intestinal barrier dysfunction has significant relevance to the development of interventions to promote healthy aging.


Assuntos
Envelhecimento , Longevidade , Animais , Camundongos , Envelhecimento/patologia , Drosophila/fisiologia , Mucosa Intestinal/metabolismo , Intestinos/fisiologia , Longevidade/fisiologia
10.
Nature ; 617(7961): 581-591, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37165188

RESUMO

The spatiotemporal structure of the human microbiome1,2, proteome3 and metabolome4,5 reflects and determines regional intestinal physiology and may have implications for disease6. Yet, little is known about the distribution of microorganisms, their environment and their biochemical activity in the gut because of reliance on stool samples and limited access to only some regions of the gut using endoscopy in fasting or sedated individuals7. To address these deficiencies, we developed an ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion. Collection of 240 intestinal samples from 15 healthy individuals using the device and subsequent multi-omics analyses identified significant differences between bacteria, phages, host proteins and metabolites in the intestines versus stool. Certain microbial taxa were differentially enriched and prophage induction was more prevalent in the intestines than in stool. The host proteome and bile acid profiles varied along the intestines and were highly distinct from those of stool. Correlations between gradients in bile acid concentrations and microbial abundance predicted species that altered the bile acid pool through deconjugation. Furthermore, microbially conjugated bile acid concentrations exhibited amino acid-dependent trends that were not apparent in stool. Overall, non-invasive, longitudinal profiling of microorganisms, proteins and bile acids along the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease.


Assuntos
Ácidos e Sais Biliares , Microbioma Gastrointestinal , Intestinos , Metaboloma , Proteoma , Humanos , Ácidos e Sais Biliares/metabolismo , Microbioma Gastrointestinal/fisiologia , Proteoma/metabolismo , Bactérias/classificação , Bactérias/isolamento & purificação , Bacteriófagos/isolamento & purificação , Bacteriófagos/fisiologia , Fezes/química , Fezes/microbiologia , Fezes/virologia , Intestinos/química , Intestinos/metabolismo , Intestinos/microbiologia , Intestinos/fisiologia , Intestinos/virologia , Digestão/fisiologia
11.
J Transl Med ; 21(1): 349, 2023 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-37237321

RESUMO

Gut microbiota is closely related to human health and disease because, together with their metabolites, gut microbiota maintain normal intestinal peristalsis. The use of antibiotics or opioid anesthetics, or both, during surgical procedures can lead to dysbiosis and affect intestinal motility; however, the underlying mechanisms are not fully known. This review aims to discuss the effect of gut microbiota and their metabolites on postoperative intestinal motility, focusing on regulating the enteric nervous system, 5-hydroxytryptamine neurotransmitter, and aryl hydrocarbon receptor.


Assuntos
Microbioma Gastrointestinal , Humanos , Intestinos/fisiologia , Motilidade Gastrointestinal , Disbiose
12.
J Anim Physiol Anim Nutr (Berl) ; 107(5): 1198-1205, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37203256

RESUMO

Blidingia sp. is a prominent fouling green macroalga and we previously found that extracts from Blidingia sp. alleviated intestinal inflammation in mice challenged with lipopolysaccharides. However, whether these extracts are effective in weanling piglets remains unknown. In the present study, Blidingia sp. extracts were supplemented in the diet and their effects on growth performance, incidence of diarrhoea and intestinal function in weanling piglets were explored. The results showed that diets supplemented with 0.1% or 0.5% Blidingia sp. extract significantly increased average daily body weight gain and feed intake in weanling piglets. Meanwhile, piglets supplemented with 0.5% Blidingia sp. extract showed decreased incidence of diarrhoea as well as reduced fecal water and Na+ content. Furthermore, the diet supplemented with 0.5% Blidingia sp. extracts improved intestinal morphology, as indicated by the results of hematoxylin and eosin staining. Diet supplemented with 0.5% Blidingia sp. extracts also improved tight junction function, as indicated by increased expression of Occludin, Claudin-1 and Zonula occludens-1, and alleviated the inflammatory response, as indicated by decreased tumor necrosis factor-α and interleukin-6 (IL6) contents and increased IL10 levels. Taken together, our results showed that Blidingia sp. extracts had beneficial effects in weanling piglets and we suggest that Blidingia sp. extracts could be potentially used as an additive for piglets.


Assuntos
Diarreia , Intestinos , Suínos , Animais , Camundongos , Intestinos/fisiologia , Diarreia/prevenção & controle , Diarreia/veterinária , Suplementos Nutricionais , Dieta/veterinária , Ocludina , Aumento de Peso , Ração Animal/análise
13.
Food Chem ; 420: 136050, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37098305

RESUMO

The aim of the present study was to comparatively investigate the relative phytochemical profiles (phenolic content, organic and amino acids, free sugars, and other metabolites using metabolomics approach), and bioactive potentials of young (YS) and mature soybean (MS) upon in vitro simulated gastrointestinal digestion (SGID). Cumulatively, a total of 198 metabolites were identified in MS and YS, 119 metabolites in undigested YS, and a total of 136 metabolites in undigested MS, which further increased to 156 and 152 in YS and MS upon SGID, respectively. Gastric digesta of both YS and MS exhibited higher inhibitory properties towards α-amylase and DPP-IV enzymes than their intestinal digesta. Furthermore, the intestinal digesta of MS showed higher antioxidant and anti-inflammatory activities compared to the YS intestinal digesta. Overall, the results suggested that the gastrointestinal digestion of YS and MS displayed distinctive metabolic profiles together with varied bioactive potentials.


Assuntos
Metabolômica , Antioxidantes/química , Antioxidantes/metabolismo , Digestão , Intestinos/fisiologia , alfa-Amilases/química , alfa-Amilases/metabolismo
14.
Neurogastroenterol Motil ; 35(6): e14577, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37010874

RESUMO

BACKGROUND: There is no term for bloating in Spanish and distension is a very technical word. "Inflammation"/"swelling" are the most frequently used expressions for bloating/distension in Mexico, and pictograms are more effective than verbal descriptors (VDs) for bloating/distension in general GI and Rome III-IBS patients. However, their effectiveness in the general population and in subjects with Rome IV-DGBI is unknown. We analyzed the use of pictograms for assessing bloating/distension in the general population in Mexico. METHODS: The Rome Foundation Global Epidemiology Study (RFGES) in Mexico (n = 2001) included questions about the presence of VDs "inflammation"/"swelling" and abdominal distension, their comprehension, and pictograms (normal, bloating, distension, both). We compared the pictograms with the Rome IV question about the frequency of experiencing bloating/distension, and with the VDs. KEY RESULTS: "Inflammation"/"swelling" was reported by 51.5% and distension by 23.8% of the entire study population; while 1.2% and 25.3% did not comprehend "Inflammation"/"swelling" or distension, respectively. Subjects without (31.8%) or not comprehending "inflammation"/"swelling"/distension (68.4%) reported bloating/distension by pictograms. Bloating and/or distension by the pictograms were much more frequent in those with DGBI: 38.3% (95%CI: 31.7-44.9) vs. without: 14.5% (12.0-17.0); and in subjects with distension by VDs: 29.4% (25.4-33.3) vs. without: 17.2% (14.9-19.5). Among subjects with bowel disorders, those with IBS reported bloating/distension by pictograms the most (93.8%) and those with functional diarrhea the least (71.4%). CONCLUSIONS & INFERENCES: Pictograms are more effective than VDs for assessing the presence of bloating/distension in Spanish Mexico. Therefore, they should be used to study these symptoms in epidemiological research.


Assuntos
Síndrome do Intestino Irritável , Obras Pictóricas como Assunto , Humanos , Gases , Intestinos/fisiologia , Intestinos/fisiopatologia , México/epidemiologia , Cidade de Roma , Inquéritos e Questionários
15.
Am J Physiol Cell Physiol ; 324(5): C1158-C1170, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37067458

RESUMO

In Caenorhabditis elegans, rhythmic posterior body wall muscle contractions mediate the highly regular defecation cycle. These contractions are regulated by inositol-1,4,5-trisphosphate (InsP3) receptor-dependent Ca2+ oscillations in intestinal epithelial cells. Here, we find that mutations in dec-7, which encodes the nematode ortholog of the human Sushi domain-containing 2 protein (SUSD2), lead to an increase in InsP3 receptor-dependent rhythmic posterior body wall muscle contractions. DEC-7 is highly expressed in the intestinal epithelia and localizes to the cell-cell junction. The increase in rhythmic activity caused by the loss of dec-7 is dependent on the innexin gap junction protein INX-16. Moreover, DEC-7 is required for the clustering of INX-16 to the cell-cell junction of the intestinal epithelia. We hypothesize that DEC-7/SUSD2 regulates INX-16 activity to mediate the rhythmic frequency of the defecation motor program. Thus, our data indicate a critical role of a phylogenetically conserved cell-cell junction protein in mediating an ultradian rhythm in the intestinal epithelia of C. elegans.NEW & NOTEWORTHY The conserved complement group protein DEC-7/SUSD2 acts at the apical cell-cell junction of C. elegans intestinal epithelia to mediate gap junction protein organization and function to facilitate a Ca2+ wave-regulated ultradian behavior.


Assuntos
Proteínas de Caenorhabditis elegans , Ritmo Ultradiano , Animais , Humanos , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Intestinos/fisiologia , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Conexinas/metabolismo , Glicoproteínas de Membrana/metabolismo
16.
Front Immunol ; 14: 1139821, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36911704

RESUMO

Gut microbiota represents a hidden treasure vault encompassing trillions of microorganisms that inhabit the intestinal epithelial barrier of the host. In the past decade, numerous in-vitro, animal and clinical studies have revealed the profound roles of gut microbiota in maintaining the homeostasis of various physiological functions, especially immune modulation, and remarkable differences in the configuration of microbial communities between cancers and healthy individuals. In addition, although considerable efforts have been devoted to cancer treatments, there remain many patients succumb to their disease with the incremental cancer burden worldwide. Nevertheless, compared with the stability of human genome, the plasticity of gut microbiota renders it a promising opportunity for individualized treatment. Meanwhile, burgeoning findings indicate that gut microbiota is involved in close interactions with the outcomes of diverse cancer immunotherapy protocols, including immune checkpoint blockade therapy, allogeneic hematopoietic stem cell transplantation, and chimeric antigen receptor T cell therapy. Here, we reviewed the evidence for the capacity of gut microflora to modulate cancer immunotherapies, and highlighted the opportunities of microbiota-based prognostic prediction, as well as microbiotherapy by targeting the microflora to potentiate anticancer efficacy while attenuating toxicity, which will be pivotal to the development of personalized cancer treatment strategies.


Assuntos
Microbioma Gastrointestinal , Microbiota , Neoplasias , Animais , Humanos , Imunoterapia/métodos , Microbiota/fisiologia , Intestinos/fisiologia
17.
Front Immunol ; 14: 1110696, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36936939

RESUMO

Introduction: In an effort to minimize the usage of fishmeal in aquaculture, novel protein diets, including Tenebrio molitor, cottonseed protein concentrate, Clostridium autoethanogenum, and Chlorella vulgaris were evaluated for their potential to replace fishmeal. Nevertheless, comprehensive examinations on the gut health of aquatic animals under an alternate feeding strategy when fed novel protein diets are vacant. Methods: Five isonitrogenous and isolipidic diets containing various proteins were manufactured, with a diet consisting of whole fishmeal serving as the control and diets containing novel proteins serving as the experimental diets. Largemouth bass (Micropterus salmoides) with an initial body weight of 4.73 ± 0.04g employed as an experimental animal and given these five diets for the first 29 days followed by a fishmeal diet for the next 29 days. Results: The results of this study demonstrated that the growth performance of novel protein diets in the second stage was better than in the first stage, even though only the C. vulgaris diet increased antioxidant capacity and the cottonseed protein concentrate diet decreased it. Concerning the intestinal barriers, the C. autoethanogenum diet lowered intestinal permeability and plasma IL-1ß/TNF-α. In addition, the contents of intestinal immunological factors, namely LYS and sIgA-like, were greater in C. vulgaris than in fishmeal. From the data analysis of microbiome and metabolome, the levels of short chain fatty acids (SCFAs), anaerobic bacteria, Lactococcus, and Firmicutes were significantly higher in the C. autoethanogenum diet than in the whole fishmeal diet, while the abundance of Pseudomonas, aerobic bacteria, Streptococcus, and Proteobacteria was lowest. However, no extremely large differences in microbiota or short chain fatty acids were observed between the other novel protein diets and the whole fishmeal diet. In addition, the microbiota were strongly connected with intestinal SCFAs, lipase activity, and tight junctions, as shown by the Mantel test and Pearson's correlation. Discussion: Taken together, according to Z-score, the ranking of advantageous functions among these protein diets was C. autoethanogenum diet > C. vulgaris diet > whole fishmeal diet > cottonseed protein concentrate > T. molitor diet. This study provides comprehensive data illustrating a mixed blessing effect of novel protein diets on the gut health of juvenile largemouth bass under an alternate feeding strategy.


Assuntos
Ração Animal , Bass , Dieta , Intestinos , Bass/crescimento & desenvolvimento , Bass/imunologia , Bass/fisiologia , Multiômica , Intestinos/química , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Intestinos/fisiologia , Proteínas de Peixes , Animais , Ração Animal/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Dieta/efeitos adversos , Dieta/métodos , Dieta/veterinária , Ácidos Graxos/análise , Óleo de Sementes de Algodão , Proteínas de Plantas , Chlorella vulgaris , Tenebrio , Insetos Comestíveis
18.
Curr Top Dev Biol ; 153: 281-326, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36967198

RESUMO

The intestinal epithelium plays a key role in digestion and protection against external pathogens. This tissue presents a high cellular turnover with the epithelium being completely renewed every 5days, driven by intestinal stem cells (ISCs) residing in the crypt bases. To sustain this dynamic renewal of the intestinal epithelium, the maintenance, proliferation, and differentiation of ISCs must be precisely controlled. One of the central pathways supporting ISC maintenance and dynamics is the Wnt pathway. In this chapter, we examine the role of Wnt signaling in intestinal epithelial homeostasis and tissue regeneration, including mechanisms regulating ISC identity and fine-tuning of Wnt pathway activation. We extensively discuss the contribution of the stem cell niche in maintaining Wnt signaling in the intestinal crypts that support ISC functions. The integration of these findings highlights the complex interplay of multiple niche signals and cellular components sustaining ISC behavior and maintenance, which together supports the immense plasticity of the intestinal epithelium.


Assuntos
Mucosa Intestinal , Via de Sinalização Wnt , Via de Sinalização Wnt/fisiologia , Proliferação de Células , Mucosa Intestinal/metabolismo , Diferenciação Celular/fisiologia , Células-Tronco , Intestinos/fisiologia
19.
MMW Fortschr Med ; 165(5): 11, 2023 03.
Artigo em Alemão | MEDLINE | ID: mdl-36894835
20.
J Anim Sci ; 1012023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36961867

RESUMO

An experiment was conducted to test the hypothesis that inclusion of a conventional torula yeast or a torula yeast produced from forestry byproducts (i.e., woody torula yeast) in diets for weanling pigs instead of fish meal and plasma protein improves growth performance and intestinal health of pigs. A total of 120 weanling pigs (6.53 ± 0.78 kg) were allotted to three treatments with ten replicate pens per diet. Pigs were fed one of three diets from days 1 to 14 post-weaning (phase 1), whereas all pigs were fed a common diet in phase 2 (days 15 to 28). The three treatments in phase 1 included a control diet with 5% fish meal, 3.5% plasma protein, and no torula yeast. The second diet contained 1.5% fish meal, 14% woody torula yeast, and no plasma protein, whereas the third diet contained 1.5% fish meal, 14% conventional torula yeast, and no plasma protein. Fecal scores were assessed every other day. On day 7, one pig per pen was euthanized to collect ileal tissue and mucosa for determination of morphology and for ribonucleic acid (RNA) sequencing analysis. At the end of phases 1 and 2, blood samples were collected and concentrations of cytokines, plasma urea nitrogen (PUN), peptide YY, immunoglobulin G, total protein, and albumin were analyzed. Results indicated that both torula yeast sources could replace fish meal and plasma protein without affecting growth performance, intestinal morphology, or blood characteristics of pigs. Pigs fed a diet containing torula yeast had improved (P < 0.05) fecal scores during phase 1. Pigs fed the conventional torula yeast diet had greater (P < 0.05) concentration of interleukin-2 compared with pigs fed the control diet. On day 14, greater (P < 0.05) concentrations of interleukin-4 and interleukin-10 were observed in pigs fed the diet containing the woody torula yeast or conventional torula yeast compared with pigs fed the control diet. Results from the RNA sequencing indicated that 19 of 24 analyzed genes involved in digestion and absorption of protein and vitamins were downregulated in pigs fed the diet containing woody torula yeast compared with pigs fed the control diet. However, only two genes (i.e., ANKS4B and FAM54A) were downregulated in pigs fed the woody torula yeast diet compared with the conventional torula yeast diet. In conclusion, using woody or conventional torula yeast instead of fish meal and plasma protein in the phase 1 diet for weanling pigs may improve intestinal health without influencing growth performance of pigs.


A torula yeast produced using forestry byproducts (i.e., woody torula yeast) had been demonstrated to have greater concentrations of digestible amino acids and phosphorus than fish meal, which indicates that the woody torula yeast can be used as a protein source for weanling pigs. However, information about effects of the woody torula yeast and conventional torula yeast on intestinal health and immune response are limited. Therefore, an experiment was conducted to test the hypothesis that the woody torula yeast improves intestinal health of pigs to a greater extent than conventional torula yeast. Results demonstrated that both woody torula yeast and conventional torula yeast could replace fish meal and plasma protein without negatively affecting growth performance, intestinal morphology, or blood characteristics of pigs. Regardless of source, torula yeast also improved fecal scores during the first 2 wk post-weaning and increased concentrations of anti-inflammatory cytokines in plasma of pigs. Therefore, dietary inclusion of torula yeast in diets for weanling pigs may represent a strategy to improve intestinal health of weanling pigs, but no differences between woody torula yeast and conventional torula yeast were observed.


Assuntos
Candida , Dieta , Suplementos Nutricionais , Intestinos , Sus scrofa , Sus scrofa/crescimento & desenvolvimento , Sus scrofa/fisiologia , Masculino , Feminino , Desmame , Distribuição Aleatória , Intestinos/fisiologia , Dieta/veterinária , Fezes/microbiologia , Animais
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