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1.
Commun Biol ; 7(1): 787, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951550

RESUMO

Adipose tissue development begins in the fetal period, and continues to expand after birth. Dysregulation of adipose tissue during weaning may predispose individuals to lifelong metabolic disorders. However, the developmental remodeling of adipose tissue during weaning remains largely unexplored. Here we comprehensively compare the changes in mouse subcutaneous white adipose tissue from 7 days after birth to 7 days after weaning using single-cell RNA sequencing along with other molecular and histologic assays. We characterize the developmental trajectory of preadipocytes and indicate the commitment of preadipocytes with beige potential during weaning. Meanwhile, we find immune cells unique to weaning period, whose expression of extracellular matrix proteins implies potential regulation on preadipocyte. Finally, the strongest cell-cell interaction during weaning determined by the TGFß ligand-receptor pairs is between preadipocytes and endotheliocytes. Our results provide a detailed and unbiased cellular landscape and offer insights into the potential regulation of adipose tissue remodeling during weaning.


Assuntos
Tecido Adiposo Branco , Análise de Célula Única , Gordura Subcutânea , Desmame , Animais , Camundongos , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/citologia , Gordura Subcutânea/metabolismo , Gordura Subcutânea/citologia , Camundongos Endogâmicos C57BL , Adipócitos/metabolismo , Adipócitos/citologia , Masculino , Feminino
2.
Sci Rep ; 14(1): 15466, 2024 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-38965336

RESUMO

This study aimed to evaluate the efficacy of Lactiplantibacillus argentoratensis AGMB00912 (LA) in reducing Salmonella Typhimurium infection in weaned piglets. The investigation focused on the influence of LA on the gut microbiota composition, growth performance, and Salmonella fecal shedding. The results indicated that LA supplementation significantly improved average daily gain and reduced the prevalence and severity of diarrhea. Fecal analysis revealed reduced Salmonella shedding in the LA-supplemented group. Furthermore, LA notably altered the composition of the gut microbiota, increasing the levels of beneficial Bacillus and decreasing those of harmful Proteobacteria and Spirochaetes. Histopathological examination showed less intestinal damage in LA-treated piglets than in the controls. The study also observed that LA affected metabolic functions related to carbohydrate, amino acid, and fatty acid metabolism, thereby enhancing gut health and resilience against infection. Short-chain fatty acid concentrations in the feces were higher in the LA group, suggesting improved gut microbial activity. LA supplementation enriched the population of beneficial bacteria, including Streptococcus, Clostridium, and Bifidobacterium, while reducing the number of harmful bacteria, such as Escherichia and Campylobacter. These findings indicate the potential of LA as a probiotic alternative for swine nutrition, offering protective effects to the gut microbiota against Salmonella infection.


Assuntos
Fezes , Microbioma Gastrointestinal , Probióticos , Desmame , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Suínos , Projetos Piloto , Probióticos/administração & dosagem , Fezes/microbiologia , Salmonelose Animal/microbiologia , Doenças dos Suínos/microbiologia , Doenças dos Suínos/prevenção & controle , Lactobacillaceae , Salmonella typhimurium/efeitos dos fármacos
4.
Microbiome ; 12(1): 131, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030599

RESUMO

BACKGROUND: The average daily gain (ADG) of preweaning calves significantly influences their adult productivity and reproductive performance. Gastrointestinal microbes are known to exert an impact on host phenotypes, including ADG. The aim of this study was to investigate the mechanisms by which gastrointestinal microbiome regulate ADG in preweaning calves and to further validate them by isolating ADG-associated rumen microbes in vitro. RESULTS: Sixteen Holstein heifer calves were selected from a cohort with 106 calves and divided into higher ADG (HADG; n = 8) and lower ADG (LADG; n = 8) groups. On the day of weaning, samples of rumen contents, hindgut contents, and plasma were collected for rumen metagenomics, rumen metabolomics, hindgut metagenomics, hindgut metabolomics, and plasma metabolomics analyses. Subsequently, rumen contents of preweaning Holstein heifer calves from the same dairy farm were collected to isolate ADG-associated rumen microbes. The results showed that the rumen microbes, including Pyramidobacter sp. C12-8, Pyramidobacter sp. CG50-2, Pyramidobacter porci, unclassified_g_Pyramidobacter, Pyramidobacter piscolens, and Acidaminococcus fermentans, were enriched in the rumen of HADG calves (LDA > 2, P < 0.05). Enrichment of these microbes in HADG calves' rumen promoted carbohydrate degradation and volatile fatty acid production, increasing proportion of butyrate in the rumen and ultimately contributing to higher preweaning ADG in calves (P < 0.05). The presence of active carbohydrate degradation in the rumen was further suggested by the negative correlation of the rumen microbes P. piscolens, P. sp. C12-8 and unclassified_g_Pyramidobacter with the rumen metabolites D-fructose (R < - 0.50, P < 0.05). Widespread positive correlations were observed between rumen microbes (such as P. piscolens, P. porci, and A. fermentans) and beneficial plasma metabolites (such as 1-pyrroline-5-carboxylic acid and 4-fluoro-L-phenylalanine), which were subsequently positively associated with the growth rate of HADG calves (R > 0.50, P < 0.05). We succeeded in isolating a strain of A. fermentans from the rumen contents of preweaning calves and named it Acidaminococcus fermentans P41. The in vitro cultivation revealed its capability to produce butyrate. In vitro fermentation experiments demonstrated that the addition of A. fermentans P41 significantly increased the proportion of butyrate in the rumen fluid (P < 0.05). These results further validated our findings. The relative abundance of Bifidobacterium pseudolongum in the hindgut of HADG calves was negatively correlated with hindgut 4-hydroxyglucobrassicin levels, which were positively correlated with plasma 4-hydroxyglucobrassicin levels, and plasma 4-hydroxyglucobrassicin levels were positively correlated with ADG (P < 0.05). CONCLUSIONS: This study's findings unveil that rumen and hindgut microbes play distinctive roles in regulating the preweaning ADG of Holstein heifer calves. Additionally, the successful isolation of A. fermentans P41 not only validated our findings but also provided a valuable strain resource for modulating rumen microbes in preweaning calves. Video Abstract.


Assuntos
Microbioma Gastrointestinal , Rúmen , Desmame , Animais , Bovinos , Rúmen/microbiologia , Rúmen/metabolismo , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , Bactérias/genética , Feminino , Fermentação , Metagenômica/métodos , Metabolômica , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/análise , Aumento de Peso , Butiratos/metabolismo
5.
Nutrients ; 16(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38999800

RESUMO

In this study, we investigated the effect of monobutyrin (MB) on the gut microbiota and intestinal health of weaned mice. MB was administered via gavage to 21-day-old weaned mice. Samples of small intestinal and ileal contents were collected on day 1, day 7, and day 21 post-administration. Seven days of MB administration enhanced the mucin layer and morphological structure of the intestine and the integrity of the intestinal brush border. Both MB and sodium butyrate (SB) accelerated tight junction development. Compared to SB, MB modulated intestinal T cells in a distinct manner. MB increased the ratio of Treg cells in the small intestine upon the cessation of weaning. After 21 days of MB administration, enhancement of the villus structure of the ileum was observed. MB increased the proportion of Th17 cells in the ileum. MB facilitated the transition of the small intestinal microbiota toward an adult microbial community structure and enhanced the complexity of the microbial community structure. An increase in Th17 cells enhanced intestinal barrier function. The regulatory effect of MB on Th17 cells may occur through the intestinal microbiota. Therefore, MB can potentially be used to promote intestinal barrier function, especially for weaning animals, with promising application prospects.


Assuntos
Microbioma Gastrointestinal , Mucosa Intestinal , Células Th17 , Desmame , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Masculino , Camundongos Endogâmicos C57BL , Íleo/microbiologia , Intestino Delgado/microbiologia , Intestino Delgado/efeitos dos fármacos , Ácido Butírico/farmacologia , Ácido Butírico/metabolismo , Junções Íntimas/metabolismo , Junções Íntimas/efeitos dos fármacos , Linfócitos T Reguladores , Função da Barreira Intestinal
6.
Nutrients ; 16(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38999826

RESUMO

The aim of this study was to investigate whether age at introduction of solid foods in preterm infants influences growth in the first year of life. This was a prospective observational study in very low birth weight infants stratified to an early (<17 weeks corrected age) or a late (≥17 weeks corrected age) feeding group according to the individual timing of weaning. In total, 115 infants were assigned to the early group, and 82 were assigned to the late group. Mean birth weight and gestational age were comparable between groups (early: 926 g, 26 + 6 weeks; late: 881 g, 26 + 5 weeks). Mean age at weaning was 13.2 weeks corrected age in the early group and 20.4 weeks corrected age in the late group. At 12 months corrected age, anthropometric parameters showed no significant differences between groups (early vs. late, mean length 75.0 vs. 74.1 cm, weight 9.2 vs. 8.9 kg, head circumference 45.5 vs. 45.0 cm). A machine learning model showed no effect of age at weaning on length and length z-scores at 12 months corrected age. Infants with comorbidities had significantly lower anthropometric z-scores compared to infants without comorbidities. Therefore, regardless of growth considerations, we recommend weaning preterm infants according to their neurological abilities.


Assuntos
Desenvolvimento Infantil , Alimentos Infantis , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Desmame , Humanos , Estudos Prospectivos , Recém-Nascido Prematuro/crescimento & desenvolvimento , Recém-Nascido , Feminino , Masculino , Lactente , Desenvolvimento Infantil/fisiologia , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Idade Gestacional , Antropometria
7.
Nutrients ; 16(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38999893

RESUMO

A multicenter cross-sectional study was conducted among 245 experienced Spanish paediatricians, who completed an online survey based on clinically relevant topics in nutrition during the first two years of life and their recommendations to parents in daily clinical practice. Most participants advise about the choking risk associated with baby-led weaning (BLW) and more than 60% consider that infants can receive an insufficient variety and quantity of nutrients with this practice. The general opinion is that there is a lack of evidence for delaying the introduction of gluten and other allergenic foods in the complementary feeding of healthy infants. Most participants agree/strongly agree that two servings of dairy products are the adequate daily amount in a diversified diet and 93.4% disagree/strongly disagree with the use of vegetal beverages under 1 year of life. There is a general agreement to avoid added salt and sugar before 12 months of life, the consideration that organic foods do not have a better nutritional profile than non-organic ones, and the limitations of vegetarian diets especially for adequate provision of micronutrients. Overall, there is an adequate knowledge of the new trends by paediatricians and younger ones seemed more in favor of them and interested in receiving more information on most topics.


Assuntos
Fenômenos Fisiológicos da Nutrição do Lactente , Pediatras , Humanos , Lactente , Espanha , Estudos Transversais , Feminino , Masculino , Pediatras/estatística & dados numéricos , Inquéritos e Questionários , Atenção Primária à Saúde , Adulto , Recém-Nascido , Desmame , Pré-Escolar , Estado Nutricional
8.
Sci Rep ; 14(1): 15783, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982122

RESUMO

Peyer's patches (PPs), which contain an abundance of B and T cells, play a key role in inducing pivotal immune responses in the intestinal tract. PPs are defined as aggregated lymph follicles, which consist of multiple lymph follicles (LFs) that may interact with each other in a synergistic manner. LFs are thought to be spherical in shape; however, the characteristics of their structure are not fully understood. To elucidate changes in the structure of PPs as individuals grow, we generated serial 2D sections from entire PPs harvested from mice at 2, 4, and 10 weeks of age and performed a 3D analysis using a software, Amira. Although the number of LFs in PPs was not changed throughout the experiment, the volume and surface area of LFs increased significantly, indicating that LFs in PPs develop continuously by recruiting immune cells, even after weaning. In response to the dramatic changes in the intestinal environment after weaning, the development of germinal centers (GCs) in LFs was observed at 4 and 10 weeks (but not 2 weeks) of age. In addition, GCs gradually began to form away from the center of LFs and close to the muscle layer where export lymphatic vessels develop. Importantly, each LF was joined to the adjacent LF; this feature was observed even in preweaning nonactivated PPs. These results suggest that PPs may have a unique organization and structure that enhance immune functions, allowing cells in LFs to have free access to adjacent LFs and egress smoothly from PPs to the periphery upon stimulation after weaning.


Assuntos
Nódulos Linfáticos Agregados , Desmame , Animais , Nódulos Linfáticos Agregados/imunologia , Camundongos , Centro Germinativo/imunologia , Linfócitos B/imunologia , Junções Intercelulares
9.
Distúrbios Comun. (Online) ; 36(1): e64339, 17/06/2024.
Artigo em Inglês, Português | LILACS | ID: biblio-1556340

RESUMO

Introdução: A alimentação aparece em todas as explicações sobre os processos e ações humanas, o que confirma o fato de não ser uma conduta natural, mas efeito da interação entre indivíduos, inaugurada na relação mãe-bebê. Objetivo: Identificar apagamentos, lapsos e resistência nas memórias de mães de crianças, adolescentes e jovens adultos primogênitos, sobre o processo de alimentação de seus filhos. Método: descritivo, exploratório realizado com mães de crianças, adolescentes e adultos com desenvolvimento típico que responderam a um questionário sobre a alimentação. Resultados: As perguntas relativas à amamentação e ao desmame foram respondidas de forma assertiva, mostrando que estes são fatos simbólicos, que marcam a lembrança materna. Conclusão: As lembranças maternas sobre as cenas alimentares com seus filhos mostram os movimentos de união e separação entre o par interacional. É possível apontar que apenas para as perguntas relativas à amamentação e ao desmame as respostas são totalmente assertivas, indiciando que são fatos simbólicos que marcam a memória materna. (AU)


Introduction: Feeding appears in all explanations about human processes and actions, which confirms the fact that it is not a natural behavior, but an effect of the interaction between individuals, initiated in the mother-baby relationship. Objective: To identify erasures, lapses and resistance in the memories of mothers of first-born children, adolescents and young adults, about the process of feeding their children. Method: descriptive, exploratory carried out with mothers of children, adolescents and adults with typical development who responded to a questionnaire about nutrition. Results: Questions regarding breastfeeding and weaning were answered assertively, showing that these are symbolic facts, which mark maternal memories. Conclusion: Maternal memories of eating scenes with their children show the movements of union and separation between the interactional pair. It is possible to point out that only for the questions related to breastfeeding and weaning the answers are completely assertive, indicating that they are symbolic facts that mark maternal memory. (AU)


Introducción: La alimentación aparece en todas las explicaciones sobre los procesos y acciones humanas, lo que confirma que no es un comportamiento natural, sino un efecto de la interacción entre individuos, iniciada en la relación madre-bebé. Objetivo: Identificar borramientos, lapsos y resistencias en los recuerdos de madres de primogénitos, adolescentes y adultos jóvenes, sobre el proceso de alimentación de sus hijos. Método: descriptivo, exploratorio realizado con madres de niños, adolescentes y adultos con desarrollo típico que respondieron un cuestionario sobre nutrición. Resultados: Las preguntas sobre lactancia materna y destete fueron respondidas de manera asertiva, demostrando que se trata de hechos simbólicos, que marcan los recuerdos maternos. Conclusión: Los recuerdos maternos de escenas de comida con sus hijos muestran los movimientos de unión y separación entre la pareja interaccional. Es posible señalar que sólo para las preguntas relacionadas con la lactancia materna y el destete las respuestas son completamente asertivas, indicando que son hechos simbólicos que marcan la memoria materna. (AU)


Assuntos
Humanos , Feminino , Rememoração Mental , Comportamento Alimentar , Mães/psicologia , Desmame , Aleitamento Materno , Desenvolvimento Infantil , Inquéritos e Questionários , Nutrição da Criança , Nutrição do Adolescente , Relações Mãe-Filho/psicologia
10.
Sci Rep ; 14(1): 13728, 2024 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877087

RESUMO

When weaning offspring, female mammals limit nursing opportunities. This study aimed to investigate whether imposing a gradual reduction in daily contact time, by separating cows from their calves as an attempt to stimulate weaning, reduced dairy cows' motivation to nurse their calves. For seven weeks, 84 Holstein-Friesian cow-calf pairs were housed with either full-time (23 h contact/d), part-time (10 h contact/d), or no contact. In the following two weeks, half of full- and part-time pairs were subjected to reduced contact (50% of initial contact in week 8, 25% of initial contact in week 9), while the other half continued with unchanged contact. In weeks 8 and 9, cows' motivation to obtain full contact to and opportunity to nurse their calves was measured using weighted push gates using a novel maximum price paid method providing an alternative choice to the cows to reduce frustration. Cows with reduced calf contact were more motivated than cows with unchanged contact; however, cows used the alternative choice less than expected. The results show that cows' motivation for full calf contact and opportunity to nurse increases when daily calf contact is reduced, illustrating that dairy cows are motivated to continue nursing their 9- to 10-week-old calves.


Assuntos
Motivação , Animais , Bovinos , Feminino , Indústria de Laticínios , Desmame , Comportamento Animal/fisiologia
11.
Anim Sci J ; 95(1): e13972, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38923622

RESUMO

High grain feeding or weaning, which could compromise the rumen epithelium by increasing ruminal short-chain fatty acid (SCFA) concentrations with pH reduction, is associated with high levels of ruminal toll-like receptor 5 (TLR5). This study aimed to determine the role of TLR5 in the rumen epithelium. Immunohistochemistry revealed that TLR5 was localized in cells on the basal side (i.e., basal and spinous layers) rather than in the granular layer in the rumen epithelium, where tight junctions are most potent, in pre- and post-weaning calves (n = 9). Primary bovine rumen epithelial cells (BRECs) obtained from Holstein cows (n = 3) were cultured to investigate the factors that upregulate TLR5; however, SCFA, low pH (pH 5.6), BHBA, L-lactate, D-lactate, and LPS did not upregulate TLR5 gene expression in BREC. Primary BREC treated with flagellin (TLR5 ligand) had higher expression of interleukin-1ß (IL-1ß) (P < 0.05) than BREC treated with vehicle. In addition, BREC treated with IL-1ß had higher expression of antimicrobial peptides and C-X-C motif chemokine ligand 8 than BREC treated with vehicle (P < 0.05). These results suggest that ruminal TLR5 may recognize epithelial disruption via flagellin and mediate the immune response via IL-1ß during high-grain feeding or weaning.


Assuntos
Células Epiteliais , Expressão Gênica , Interleucina-1beta , Interleucina-8 , Rúmen , Receptor 5 Toll-Like , Animais , Receptor 5 Toll-Like/genética , Receptor 5 Toll-Like/metabolismo , Rúmen/metabolismo , Bovinos/metabolismo , Células Epiteliais/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Células Cultivadas , Interleucina-8/metabolismo , Interleucina-8/genética , Desmame , Peptídeos Antimicrobianos/genética , Peptídeos Antimicrobianos/metabolismo , Flagelina/farmacologia , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/farmacologia , Ligantes , Regulação para Cima
12.
Microsc Microanal ; 30(3): 552-563, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833344

RESUMO

Grainyhead-like 2 (Grhl2) is a transcription factor that regulates cell adhesion genes in mammary ductal development and serves as a repressor of the epithelial-mesenchymal transition. Conversely, Ovo-like2 (Ovol2) is a target gene of Grhl2 but functions as a substitute in Grhl2-deficient mice, facilitating successful epithelial barrier formation and lumen expansion in kidney-collecting ductal epithelial cells. Our objective was to examine the expression patterns of Grhl2, Ovol2, and their associated genes during the intricate phases of mouse mammary gland development. The mRNA expression of Grhl2 and Ovol2 increased after pregnancy. We observed Grhl2 protein presence in the epithelial cell's region, coinciding with acini formation, and its signal significantly correlated with E-cadherin (Cdh1) expression. However, Ovol2 was present in the epithelial region without a correlation with Cdh1. Similarly, Zeb1, a mesenchymal transcription factor, showed Cdh1-independent expression. Subsequently, we explored the interaction between Rab25, a small G protein, and Grhl2/Ovol2. The expressions of Grhl2 and Ovol2 exhibited a strong correlation with Rab25 and claudin-4, a tight junction protein. These findings suggest that Grhl2 and Ovol2 may collaborate to regulate genes associated with cell adhesion and are crucial for maintaining epithelial integrity during the different phases of mammary gland development.


Assuntos
Lactação , Glândulas Mamárias Animais , Fatores de Transcrição , Desmame , Animais , Feminino , Camundongos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Glândulas Mamárias Animais/crescimento & desenvolvimento , Glândulas Mamárias Animais/metabolismo , Gravidez , Lactação/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Células Epiteliais/metabolismo , Claudina-4/genética , Claudina-4/metabolismo , Caderinas
13.
Anim Biotechnol ; 35(1): 2362640, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38860902

RESUMO

In this study, we investigated the effects of supplemental Glycyrrhiza polysaccharide (GCP) on growth performance and intestinal health of weaned piglets. Ninety piglets weaned at 28 days of age were randomly allocated to three groups with five replicates per treatment. Piglets were fed the following diets for 28 days: (1) CON (control group), basal diet; (2) G500, CON + 500 mg/kg GCP; (3) G1000, CON + 1000 mg/kg GCP. The results showed that supplementation with 1000 mg/kg GCP increased the average daily gain (ADG) and decreased the feed-to-gain ratio (F/G) (P < 0.05). Serum diamine oxidase (DAO) and D-lactic acid (DL-A) levels were lower in the G1000 group (P < 0.05). Dietary GCP 1000 mg/kg improved mucosal trypsin activity in the duodenum, jejunum and ileum and increased lipase and amylase activity in the jejunum (P < 0.05). Moreover, in the G1000 group, ZO-1, claudin 1 and occludin levels were increased in the jejunum mucosa, whereas interleukin-1ß (IL-1ß) and IL-6 levels were decreased (P < 0.05). The 16S rRNA gene analysis indicated that dietary 1000 mg/kg GCP altered the jejunal microbial community, with increased relative abundances of beneficial bacteria. In conclusion, dietary GCP 1000 mg/kg can improve growth performance, digestive enzyme activity, intestinal immunity, barrier function and microbial community in weaned piglets.


Assuntos
Ração Animal , Suplementos Nutricionais , Glycyrrhiza , Polissacarídeos , Desmame , Animais , Polissacarídeos/farmacologia , Polissacarídeos/administração & dosagem , Suínos/crescimento & desenvolvimento , Ração Animal/análise , Glycyrrhiza/química , Intestinos/efeitos dos fármacos , Dieta/veterinária , Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino
14.
Life Sci ; 350: 122765, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38830506

RESUMO

BACKGROUND: Malnutrition is a common problem in developing countries, and the impact of severe malnutrition on optimal treatment outcomes of chemotherapy in pediatric cancer patients is well documented. However, despite being a more prevalent and distinct entity, moderate malnutrition is until now unexplored for its effects on treatment outcomes. AIMS: In this study we aimed to investigate the molecular basis of altered pharmacokinetics and cardiotoxicity of doxorubicin observed in early-life chronic moderate protein deficiency malnutrition. MATERIALS AND METHODS: We developed an animal model of early-life moderate protein-deficiency malnutrition and validated it using clinical samples. This model was used to study pharmacokinetic and toxicity changes and was further utilized to study the molecular changes in liver and heart to get mechanistic insights. KEY FINDINGS: Here we show that moderate protein-deficiency malnutrition in weanling rats causes changes in drug disposition in the liver by modification of hepatic ABCC3 and MRP2 transporters through the TNFα signalling axis. Furthermore, malnourished rats in repeat-dose doxorubicin toxicity study showed higher toxicity and mortality. A higher accumulation of doxorubicin in the heart was observed which was associated with alterations in cardiac metabolic pathways and increased cardiotoxicity. SIGNIFICANCE: Our findings indicate that moderate malnutrition causes increased susceptibility towards toxic side effects of chemotherapy. These results may necessitate further investigations and new guidelines on the dosing of chemotherapy in moderately malnourished pediatric cancer patients.


Assuntos
Cardiotoxicidade , Doxorrubicina , Animais , Doxorrubicina/farmacocinética , Doxorrubicina/efeitos adversos , Ratos , Cardiotoxicidade/etiologia , Masculino , Desmame , Fígado/metabolismo , Desnutrição Proteico-Calórica/metabolismo , Humanos , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/toxicidade , Feminino , Modelos Animais de Doenças , Ratos Wistar
15.
Vet Microbiol ; 295: 110162, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38941767

RESUMO

Postweaning diarrhea (PWD) is a multifactorial disease caused by different aetiological agents, like viruses or bacteria and where the role of the microbiota remains unclear. The aim of this study was to assess differences between healthy and diarrheic weaned pigs concerning the prevalence of pathogens and changes in the intestinal microbiota. Eighteen farms with PWD were selected and 277 fecal samples were collected (152 diarrheic vs 125 healthy). Presence of Rotavirus A (RVA), B (RVB), C (RVC) and Porcine Epidemic Diarrhea Virus (PEDV), virulence factors of Escherichia coli and Clostridioides difficile were analyzed by PCR. Finally, the microbiota composition was also study by 16 S rRNA sequencing on 148 samples (102 diarrheic vs 46 healthy). RVA (53.95 % vs 36 %, p=0.04) and RVB (49.67 % vs 28.8 %, p<0.001) were more frequent in diarrheic animals. Furthermore, RVA viral load was higher in diseased animals. VT2 toxin was significantly associated with diarrhea, whereas other virulence factors were not. Presence of C. difficile and PEDV was almost negligible. Regarding microbiota changes, Fusobacteriota phylum was more frequent in diarrheic samples and Ruminococcaceae family in healthy penmates. During the first week postweaning, Enterobacteriace and Campylobacteria were enriched in animals presenting diarrhea. Furthermore, Lactobacillus was detected in those individuals with no RVA infection. In conclusion, RVA seems to play a primary role in PWD. Classic E. coli virulence factors were not associated with diarrhea, indicating the need for revising their implication in disease. Moreover, Lactobacillus was found frequently in animals negative for RVA, suggesting some protective effect.


Assuntos
Diarreia , Fezes , Microbioma Gastrointestinal , Doenças dos Suínos , Desmame , Animais , Suínos , Diarreia/veterinária , Diarreia/microbiologia , Diarreia/virologia , Doenças dos Suínos/microbiologia , Doenças dos Suínos/virologia , Fezes/microbiologia , Fezes/virologia , Rotavirus/isolamento & purificação , Vírus da Diarreia Epidêmica Suína/isolamento & purificação , Vírus da Diarreia Epidêmica Suína/genética , Clostridioides difficile/isolamento & purificação , Clostridioides difficile/genética , Fatores de Virulência/genética , RNA Ribossômico 16S/genética , Escherichia coli/isolamento & purificação , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética
16.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38863369

RESUMO

This study was conducted to evaluate the effects of dietary organic acid blend on growth performance, antioxidant capacity, intestinal barrier function, and fecal microbiota in weaned piglets compared with antibiotic growth promoters (AGPs). A total of 90 weaned crossbred barrows (24 ±â€…1 d of age) with an initial body weight of 7.40 kg were allocated into three experimental treatments. Each treatment consisted of six replicate pens, with five piglets housed in each pen. The dietary treatments included the basal diet (NC), the basal diet supplemented with antibiotics (PC), and the basal diet supplemented with organic acid blend (OA). On day 42, one piglet per pen was randomly selected for plasma and small intestinal sample collection. The results showed that dietary AGP significantly improved growth performance and reduced diarrhea incidence compared to the NC group (P < 0.05). Dietary OA tended to increase body weight on day 42 (P = 0.07) and average daily gain from days 0 to 42 (P = 0.06) and reduce diarrhea incidence (P = 0.05). Dietary OA significantly increased plasma catalase (CAT) activity and decreased the plasma concentration of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin (IL)-8, and IL-6, which were accompanied by upregulated the relative mRNA abundance of superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1), and nuclear factor erythroid 2-related factor 2 (NRF2) in comparison to that in the NC group (P < 0.05). Moreover, pigs fed the OA diet significantly increased the ratio of villus height to crypt depth and upregulated the relative expression of zonula occludens-1 (ZO-1) and Claudin1 gene in the jejunum compared to the NC group (P < 0.05). Interestingly, dietary AGP or OA did not affect the fecal microbiota structure or volatile fatty acid content (P > 0.05). In conclusion, our results suggested that dietary OA supplementation could improve growth performance and antioxidant capacity and protect the intestinal barrier of weaned piglets, therefore, it has the potential to be considered as an alternative to AGP in the pig industry.


In the era of antibiotics prohibition, there is an urgent need to develop green and efficient alternatives to antibiotics in the current pig industry to mitigate the economic losses associated with antibiotic bans. Organic acids (OA) are a class of substances that have long been used as feed additives due to their bacteriostatic properties, the ability of reducing feed pH, increasing the activity of digestive enzymes, and other beneficial effects. This study was conducted to evaluate the effects of dietary OA on growth performance, antioxidant capacity, intestinal barrier function, and fecal microbiota structure in weaned piglets. The results showed that OA supplementation can effectively improve the growth performance and intestinal health of weaned piglets. This study provides a reference for the application of OA as an alternative to antibiotics in weaned piglets.


Assuntos
Ração Animal , Antibacterianos , Antioxidantes , Dieta , Fezes , Microbioma Gastrointestinal , Animais , Ração Animal/análise , Antioxidantes/metabolismo , Dieta/veterinária , Suínos , Masculino , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Fezes/microbiologia , Suplementos Nutricionais/análise , Desmame , Doenças dos Suínos/microbiologia , Doenças dos Suínos/prevenção & controle , Função da Barreira Intestinal
17.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38864526

RESUMO

Mastitis is an important disease with economic and welfare implications in both clinical and subclinical states. The aim of this research was to sequence the hypervariable V4 region of the 16S rRNA gene to describe the microbial diversity and taxonomy of milk from clinically healthy ewes (Rambouillet, WF = 9; Hampshire, BF = 5). Experimental ewes represented a subset of a larger study assessing the impacts of divergent dietary zinc (Zn) concentrations [1 × National Academics of Sciences, Engineering, and Medicine (NASEM) recommendations = CON or 3 × NASEM recommendations = ZnTRT] throughout late gestation and lactation. Milk was collected at four periods during early lactation (18 to 24 h, 7 d, 14 d, and 21 d postpartum) and at weaning (84 ±â€…14 d postpartum). Somatic cell counts (SCC) were quantified, averaged, and classed (low: < 500 × 103; medium: 500 × 103 - 100 × 104; high: > 100 × 104 cells/mL). Milk samples (n = 67) were sequenced to identify bacteria and archaea; the most abundant phyla were Actinobacteria, Bacteroidetes, Cyanobacteria, Euryarchaeota, Firmicutes, Fusobacteria, Lentisphaerae, Proteobacteria, Spirochaetes, Tenericutes, Saccharibacteria TM7, and Verrucomicrobia. Mastitis pathogens were among the most relatively abundant genera, including Staphylococcus, Mannheimia, Corynebacterium, and Pseudomonas. Effects of breed, dietary Zn concentration, SCC class, and their two-way interactions on milk microbiome diversity and taxonomy were assessed within early lactation (using a repeated measures model) and weaning samples. Alpha-diversity metrics included Pielou's evenness, Faith's phylogenetic diversity, and Shannon's entropy indices. The main and interactive effects between Zn treatment, breed, SCC class, and period were variable in early lactation and not evident in weaning samples. Milk from BF ewes had increased Faith's phylogenetic diversity and Shannon's entropy, and differed in unweighted UniFrac composition (P ≤ 0.10). Milk from CON ewes had a reduced rate of composition change through early lactation (P = 0.02) indicating greater microbiome stability than ZnTRT ewe milk. These results support that milk is not sterile, and breed, dietary Zn concentration, and SCC class variably affect the milk microbiome. Findings from the current study provide important foundational insights into the effects of increased dietary Zn supplementation on longitudinal changes in the milk microbiome and associations with mammary gland health and mastitis.


Mastitis is an important disease with economic and welfare implications in both clinical and subclinical states. This research described the microbial diversity and taxonomy of milk collected from clinically healthy Rambouillet (WF; n = 9) and Hampshire (BF; n = 5) primiparous ewes in a longitudinal study involving differing dietary zinc concentrations [1 × National Academics of Sciences, Engineering, and Medicine (NASEM) recommendations, CON; 3 × NASEM recommendations, ZnTRT]. Milk was collected weekly during the first 3 wk of lactation and at weaning, and somatic cell counts (SCC) were classed (low, medium, high). Mastitis pathogens were among the most relatively abundant via amplicon sequencing, including Staphylococcus, Mannheimia, Corynebacterium, and Pseudomonas. Breed, zinc treatment, and SCC class effects on milk microbiome α-diversity and ß-diversity changes and taxonomy were assessed. These effects and their two-way interactions were limited but variable in early lactation samples and not evident in weaning samples. Notably, BF ewe milk samples had increased Faith's phylogenetic diversity and increased Shannon's entropy during early lactation, and CON ewe milk samples had a reduced rate of compositional change than ZnTRT samples. These results support the existence of a milk microbiome that is variably affected by breed, increased dietary zinc concentrations, and SCC class.


Assuntos
Dieta , Suplementos Nutricionais , Lactação , Microbiota , Leite , Desmame , Zinco , Animais , Feminino , Zinco/farmacologia , Zinco/administração & dosagem , Ovinos , Leite/química , Leite/microbiologia , Microbiota/efeitos dos fármacos , Suplementos Nutricionais/análise , Dieta/veterinária , RNA Ribossômico 16S/análise , RNA Ribossômico 16S/genética , Período Pós-Parto , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Ração Animal/análise
18.
Nutrients ; 16(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38892577

RESUMO

The gut microbiota plays a crucial role in postnatal growth, particularly in modulating the development of animals during their growth phase. In this study, we investigated the effects of antibiotic-induced dysbiosis of the gut microbiota on the growth of weaning rats by administering a non-absorbable antibiotic cocktail (ABX) in water for 4 weeks. ABX treatment significantly reduced body weight and feed intake in rats. Concurrently, ABX treatment decreased microbial abundance and diversity in rat ceca, predominantly suppressing microbes associated with bile salt hydrolase (BSH) activity. Furthermore, decreased appetite may be attributed to elevated levels of glucagon-like peptide-1 (GLP-1) in the serum, along with reduced neuropeptide Y (NPY) and increased cocaine and amphetamine-regulated transcript (CART) in the hypothalamus at the mRNA level. Importantly, concentrations of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2) were decreased in the serum and liver of antibiotic-treated rats. These alterations were associated with significant down-regulation of IGF-2 mRNA in the liver and significantly decreased farnesoid X receptor (FXR) protein expression and binding to the IGF-2 promoter. These results indicate that antibiotic-induced gut microbial dysbiosis not only impacts bile acid metabolism but also diminishes rat growth through the FXR-mediated IGF-2 pathway.


Assuntos
Antibacterianos , Disbiose , Microbioma Gastrointestinal , Fator de Crescimento Insulin-Like II , Fígado , Receptores Citoplasmáticos e Nucleares , Desmame , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Antibacterianos/farmacologia , Ratos , Masculino , Fator de Crescimento Insulin-Like II/metabolismo , Ratos Sprague-Dawley , Peso Corporal/efeitos dos fármacos
19.
Codas ; 36(3): e20230108, 2024.
Artigo em Português, Inglês | MEDLINE | ID: mdl-38922259

RESUMO

PURPOSE: To analyze the influence of ankyloglossia on the prevalence and duration of exclusive breastfeeding of full-term infants up to the sixth month of life. METHODS: Prospective cohort study, carried out with 225 mother-infant dyads who were followed up in the first six months of life in a center specialized in breastfeeding in a tertiary hospital. Full-term infants with asymptomatic ankyloglossia (no need for surgery) were compared with infants without change at monthly follow-up. Ankyloglossia was diagnosed using the Bristol Tongue Assessment Tool, with a positive diagnosis being considered for those with a score less than or equal to 5 considering functional and anatomical aspects. Statistical analyzes were performed using descriptive statistics, logistic regression (weaning determinants), relative risk, and survival curves (to analyze breastfeeding duration between groups with and without ankyloglossia). RESULTS: Ankyloglossia was associated with weaning (considered even partial) before the sixth month of life. After adjusted analysis, a higher risk of weaning was detected in infants with this alteration, with a risk present from the second month of life. In the survival analysis, the duration of breastfeeding in infants with ankyloglossia was shorter when compared to children without alterations. CONCLUSION: Compared to infants with normal lingual frenulum, babies with ankyloglossia had shorter exclusive breastfeeding time, but well above the average observed in the general population. The risk of weaning for this group was also higher.


OBJETIVO: Analisar a influência da anquiloglossia na prevalência e no tempo de exclusividade do aleitamento materno de lactentes a termo até o sexto mês de vida. MÉTODOS: Estudo de coorte prospectivo, realizado com 225 díades mãe-bebê que foram acompanhadas nos seis primeiros meses de vida em centro especializado em amamentação em um hospital terciário. Lactentes a termo com anquiloglossia do tipo assintomática (sem necessidade de cirurgia) foram comparados com lactentes sem alteração em um acompanhamento mensal. O diagnóstico de anquiloglossia foi realizado através do Bristol Tongue Assessment Tool, sendo considerados com diagnóstico positivo aqueles com escore menores ou iguais a 5 considerando os aspectos funcionais e anatômicos. As análises estatísticas foram realizadas através de estatística descritiva, regressão logística (determinantes do desmame), risco relativo e curvas de sobrevivência (para analisar o tempo de aleitamento entre os grupos com e sem anquiloglossia). RESULTADOS: A anquiloglossia esteve associada com o desmame (considerado ainda que parcial) antes do sexto mês de vida. Após análise ajustada, foi detectado maior risco de desmame nos lactentes com a alteração presente, com risco presente a partir do segundo mês de vida. Na análise de sobrevida, o tempo de aleitamento nos lactentes com anquiloglossia foi menor quando comparadas às crianças sem alteração. CONCLUSÃO: Em comparação com lactentes com freio lingual normal, os bebês com anquiloglossia apresentaram tempo menor de aleitamento exclusivo, porém bem acima da média observada na população geral. O risco de desmame para este grupo também foi maior.


Assuntos
Anquiloglossia , Aleitamento Materno , Humanos , Estudos Prospectivos , Recém-Nascido , Feminino , Masculino , Lactente , Fatores de Tempo , Estudos de Coortes , Adulto , Freio Lingual/anormalidades , Desmame , Prevalência , Brasil , Fatores de Risco
20.
Animal ; 18(6): 101189, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38850575

RESUMO

Laminaria digitata is a brown seaweed rich in prebiotic polysaccharides, mainly laminarin, but its alginate-rich cell wall could compromise nutrient access. Carbohydrase supplementation, such as individual alginate lyase and carbohydrases mixture (Rovabio® Excel AP), could enhance nutrient digestibility and prebiotic potential. This study aimed to evaluate the effect of these enzymes on nutrient digestibility and gut health of weaned piglets fed with 10% L. digitata. Diets did not affect growth performance (P > 0.05). The majority of the feed fractions had similar digestibility across all diets, but the supplementation of alginate lyase increased hemicellulose digestibility by 3.3% compared to the control group (P = 0.047). Additionally, we observed that algal zinc was more readily available compared to the control group, even without enzymatic supplementation (P < 0.001). However, the increased digestibility of some minerals, such as potassium, raises concerns about potential mineral imbalance. Seaweed groups had a higher abundance of beneficial bacteria in colon contents, such as Prevotella, Oscillospira and Catenisphaera. Furthermore, the addition of alginate lyase led to a lower pH in the colon (P < 0.001) and caecum (P < 0.001) of piglets, which is possibly a result of released fermentable laminarin, and is consistent with the higher proportion of butyric acid found in these intestinal compartments. L. digitata is a putative supplement to enhance piglet gut health due to its prebiotic polysaccharides. Alginate lyase supplementation further improves nutrient digestibility and prebiotic potential. These results suggest the potential use of L. digitata and these enzymatic supplements in commercial piglet-feeding practices.


Assuntos
Ração Animal , Suplementos Nutricionais , Digestão , Glicosídeo Hidrolases , Polissacarídeo-Liases , Animais , Masculino , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Dieta/veterinária , Suplementos Nutricionais/análise , Digestão/efeitos dos fármacos , Algas Comestíveis , Microbioma Gastrointestinal/efeitos dos fármacos , Glicosídeo Hidrolases/metabolismo , Laminaria/química , Nutrientes/metabolismo , Polissacarídeo-Liases/metabolismo , Prebióticos , Suínos , Desmame
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