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BACKGROUND: Colorectal cancer screening uptake in the United States overall has increased, but racial/ethnic disparities persist and data on colonoscopy uptake by racial/ethnic subgroups are lacking. We sought to better characterize these trends and to identify predictors of colonoscopy uptake, particularly among Asian and Hispanic subgroups. STUDY: We used data from the New York City Community Health Survey to generate estimates of up-to-date colonoscopy use in Asian and Hispanic subgroups across 6 time periods spanning 2003-2016. For each subgroup, we calculated the percent change in colonoscopy uptake over the study period and the difference in uptake compared to non-Hispanic Whites in 2015-2016. We also used multivariable logistic regression to identify predictors of colonoscopy uptake. RESULTS: All racial and ethnic subgroups with reliable estimates saw a net increase in colonoscopy uptake between 2003 and 2016. In 2015-2016, compared with non-Hispanic Whites, Puerto Ricans, Dominicans, and Central/South Americans had higher colonoscopy uptake, whereas Chinese, Asian Indians, and Mexicans had lower uptake. On multivariable analysis, age, marital status, insurance status, primary care provider, receipt of flu vaccine, frequency of exercise, and smoking status were the most consistent predictors of colonoscopy uptake (≥4 time periods). CONCLUSIONS: We found significant variation in colonoscopy uptake among Asian and Hispanic subgroups. We also identified numerous demographic, socioeconomic, and health-related predictors of colonoscopy uptake. These findings highlight the importance of examining health disparities through the lens of disaggregated racial/ethnic subgroups and have the potential to inform future public health interventions.
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Asiático , Colonoscopia , Neoplasias Colorretais , Hispânico ou Latino , Grupos Populacionais dos Estados Unidos da América , Humanos , População do Caribe/estatística & dados numéricos , Colonoscopia/estatística & dados numéricos , Colonoscopia/tendências , Hispânico ou Latino/etnologia , Hispânico ou Latino/estatística & dados numéricos , Cidade de Nova Iorque/epidemiologia , População Norte-Americana/estatística & dados numéricos , Estados Unidos/epidemiologia , Asiático/estatística & dados numéricos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etnologia , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/estatística & dados numéricos , Detecção Precoce de Câncer/tendências , Brancos , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Grupos Populacionais dos Estados Unidos da América/etnologia , Grupos Populacionais dos Estados Unidos da América/estatística & dados numéricosRESUMO
BACKGROUND: Asian Americans have the lowest colorectal cancer screening uptake of any racial and ethnic group in the United States. Asian Indians are among the most under-screened Asian American subgroups, but there is limited data for this population. We sought to characterize predictors of colonoscopy use among Asian Indians in New York City. METHODS: Using 2003 to 2016 data from the New York City Community Health Survey, we identified all Asian Indian participants aged 50 years or older. We examined the association between sociodemographic and medical factors and up-to-date colonoscopy use (defined as colonoscopy within the last 10 y) using logistic regression over 4 time periods: 2003 to 2008, 2009 to 2012, 2013 to 2014, 2015 to 2016. RESULTS: On multivariable analysis, language, age, income, recent exercise, body mass index, and influenza vaccination were associated with colonoscopy uptake in 1 time period. Compared with participants who preferred English, those who preferred an Indian language were less likely to have been up-to-date in 2013 to 2014 (odds ratio 0.12, 95% CI 0.02-0.66). Individuals older than 65 years were more likely than those aged 50 to 64 years to have received a colonoscopy in 2009 to 2012 (odds ratio 3.91, 95% CI 1.49-10.24), although the risk estimates were also consistently positive in the other 3 time periods. CONCLUSIONS: Among Asian Indians living in New York City, several demographic, socioeconomic, and health-related characteristics predict colonoscopy use. These findings highlight the importance of examining determinants of colonoscopy uptake in this understudied population to inform future public health interventions.
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BACKGROUND: Colorectal cancer is the second leading cause of cancer death among Hispanic Americans. Puerto Ricans are the second largest Hispanic subgroup in the USA and the largest in New York City, but little is known about predictors of colorectal cancer screening uptake in this population. AIMS: We used the New York City Community Health Survey, a population-based telephone survey, to investigate predictors of up-to-date colonoscopy use over time among Puerto Ricans aged ≥ 50 years in NYC. METHODS: We assessed the association between sociodemographic and medical factors and up-to-date colonoscopy use (defined as colonoscopy within the last 10 years) using univariable and multivariable logistic regression over six time periods: 2003-2005, 2006-2008, 2009-2010, 2011-2012, 2013-2014, and 2015-2016. RESULTS: On multivariable analysis, age ≥ 65 years (OR 1.64-1.93 over three periods) and influenza vaccination (OR 1.86-2.17 over five periods) were the two factors most consistently associated with up-to-date colonoscopy use. Individuals without a primary care provider (OR 0.38-0.50 over three periods) and who did not exercise (OR 0.49-0.52 over two periods) were significantly less likely to have an up-to-date colonoscopy. CONCLUSIONS: Older age, influenza vaccination, having a primary care provider, and exercise are independent predictors of up-to-date colonoscopy use among Puerto Ricans in NYC. Interventions to improve screening colonoscopy uptake among Puerto Ricans should be targeted to those aged 50-64 years and who do not have a primary care provider.
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Colonoscopia , Neoplasias Colorretais , Detecção Precoce de Câncer , Hispânico ou Latino/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde , Causalidade , Colonoscopia/métodos , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/etnologia , Planejamento em Saúde Comunitária/estatística & dados numéricos , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/estatística & dados numéricos , Exercício Físico , Feminino , Inquéritos Epidemiológicos , Humanos , Vacinas contra Influenza/uso terapêutico , Masculino , Saúde das Minorias , Cidade de Nova Iorque/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Médicos de Atenção Primária/estatística & dados numéricosRESUMO
BACKGROUND: The adenoma detection rate (ADR) is a widely accepted quality benchmark for screening colonoscopy but can be burdensome to calculate. Previous studies have shown good correlation between polyp detection rate (PDR) and ADR, but this has not been validated in trainees. Additionally, the correlation between PDR and detection rates for sessile serrated polyps (SSPDR) and advanced neoplasia (ANDR) is not well studied. AIMS: We investigated the relationship between PDR and ADR, SSPDR, and ANDR in trainees. METHODS: We examined 1600 outpatient colonoscopies performed by 24 trainees at a VA hospital from 2014 to 2017. Variables collected included patient demographics, year of fellowship, colonoscopy indication, and endoscopic and histologic findings. We calculated the overall ratios of PDR to ADR, SSPDR, and ANDR to assess the correlation between measured and calculated ADR, SSPDR, and ANDR, which is equivalent to the correlation between PDR and measured ADR, SSPDR, and ANDR. RESULTS: The overall PDR, ADR, SSPDR, and ANDR were 72%, 52%, 2%, and 14%. PDR (48%) was highest in the left colon, while ADR (32%) and ANDR (7%) were highest in the right colon (p < 0.001 for all). The overall ADR/PDR, SSPDR/PDR, and ANDR/PDR ratios were 0.73, 0.03, and 0.20. Correlation between PDR and ADR was highly positive overall (r = 0.87, p < 0.0001) and stronger in the right (r = 0.91) and transverse (r = 0.94) colon than the left colon (r = 0.80). Correlation between PDR and overall SSPDR and ANDR were not statistically significant. CONCLUSIONS: PDR can serve as a surrogate measure of ADR to monitor colonoscopy quality in gastroenterology fellowship.
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Adenoma/diagnóstico , Competência Clínica/estatística & dados numéricos , Neoplasias do Colo/diagnóstico , Pólipos do Colo/diagnóstico , Colonoscopia/estatística & dados numéricos , Gastroenterologistas/estatística & dados numéricos , Idoso , Feminino , Gastroenterologia/educação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Health care services are typically consumed out of necessity, typically to recover from illness. While the consumption of health care services can be emotional given that consumers experience fear, hope, relief, and joy, surprisingly, there is little research on the role of consumer affect in health care consumption. We propose that consumer affect is a heuristic cue that drives evaluation of health care services. Drawing from cognitive appraisal theory and affect-as-information theory, this article tests a research model (N = 492) that investigates consumer affect resulting from service performance on subsequent service outcomes.
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Afeto , Serviços de Saúde , Satisfação do Paciente , Adolescente , Adulto , Comportamento do Consumidor , Emoções , Feminino , Humanos , Teoria da Informação , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Gender disparity poses a prominent obstacle to achieving effective mental health outcomes in digital healthcare. Despite women being more inclined to use mental health apps and seeking designs tailored to their specific needs, there is limited research on the factors influencing female users' engagement with these apps. The COVID-19 pandemic has further exacerbated its disproportionate impact on women's mental health. This study investigates female users' posts (n = 5538) about mental health apps during the pandemic, using data collected via a Python web crawler from Xiaohongshu, a popular female-centric social media platform in China. A mixed-methods approach used qualitative thematic analysis and quantitative descriptive statistics. Among these posts, therapeutic functionality emerged as the highest priority, followed by credibility and user experience, with specific design elements highlighted as particularly significant. These findings provide valuable insights for mental health researchers and developers, including you, aiming to create gender-tailored mobile solutions to address the mental health challenges faced by women, especially during future pandemics.
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INTRODUCTION: Youth experience significant mental health (MH) needs, and gender- and racially/ethnically-diverse youth are less likely than peers to receive care. School-based health centers (SBHCs) are a healthcare delivery model that may decrease disparities. This study examined the role of SBHCs in reducing disparities in MH care receipt among SBHC clients. METHODS: Data from electronic health records of 5,396 youth ages 12 to 21 years who visited 14 SBHCs in one California county from 2021 to 2023 were analyzed in 2023-2024 using multiple logistic regression to assess disparities in MH care receipt and depression screenings. RESULTS: Receipt of MH care from SBHCs varied significantly by gender but not age, sexual orientation, or race/ethnicity. Compared to female clients, males had reduced odds (AOR: 0.50) and gender-diverse clients had higher odds (AOR: 2.70) of receiving MH care. For receipt of depression screenings, male clients had reduced odds (AOR: 0.86); Latino clients had higher odds than white clients (AOR: 1.80); and older adolescents and young adults had higher odds than younger adolescents (AORs: 1.44 and 1.45, respectively). Receipt of follow-up MH care after a positive depression result varied only by gender, with male clients having reduced odds (AOR: 0.63). DISCUSSION: SBHCs may reach youth who are traditionally less likely to seek care in other settings, including racially/ethnically- and gender-diverse youth. As in other settings, engaging males in healthcare is an area for improvement. These findings help to demonstrate the potential of SBHCs for decreasing disparities in mental health care.
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The streak camera is one of the fastest photodetection systems, while its capability of multiplexing is particularly attractive to many applications requiring parallel data acquisition. The degree of multiplexing in a streak camera is limited by the crosstalk between input channels. We developed a technique that introducing a fixed time delay between adjacent fiber channels in a customized two-dimensional to one-dimensional fiber array to significantly reduce crosstalk both at the sample plane and at the input of a streak camera. A prototype system has been developed that supports 100 input channels, and its performance in fluorescence microscopy is demonstrated.
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Fibras Ópticas , Fenômenos Ópticos , Convallaria/citologia , Desenho de Equipamento , Processamento de Imagem Assistida por ComputadorRESUMO
BACKGROUND: School-based health centers (SBHCs) provide health care to vulnerable youth. The purpose of the study was to identify characteristics of youth who use SBHCs with the highest frequency to understand their health needs and receipt of health services. METHODS: This study examined cross-sectional survey data from adolescents in 3 urban school districts (n = 2641) to identify the characteristics of youth who use SBHCs with high frequency (10+ visits). Analyses included calculations of simple frequencies and percentages, chi-square tests of significance and multivariate regression. RESULTS: High-frequency SBHC users were more likely to have seriously considered attempting suicide (adjusted odds ratio [AOR]: 3.2), be sexually active (AOR: 6.8), and have been victimized at school (AOR: 2.2) compared to their peers who did not use the SBHC. High-frequency SBHC users were also significantly more likely than their peers to report "always" getting mental health (AOR: 7.0) and sexual health (AOR: 6.6) care when needed, and having talked with a health care provider about their moods/feelings (AOR: 3.1) and how school is going (AOR: 3.2) in the past year. CONCLUSIONS: These findings hold important relevance to demonstrating the value of SBHCs in increasing vulnerable youth's access to health care, particularly in urban settings.
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Serviços de Saúde Escolar , Serviços de Enfermagem Escolar , Adolescente , Estudos Transversais , Humanos , Fatores de Proteção , Instituições AcadêmicasRESUMO
Caloric restriction (CR) is the leading non-pharmacological intervention to delay induced and spontaneous tumors in pre-clinical models. These effects of CR are largely attributed to canonical inhibition of pro-growth pathways. However, our recent data suggest that CR impairs primary tumor growth and cancer progression in the murine 4T1 model of triple negative breast cancer (TNBC), at least in part, through reduced frequency of the myeloid-derived suppressor cells (MDSC). In the present study, we sought to determine whether injection of excess MDSCs could block regression in 4T1 tumor growth and metastatic spread in BALB/cJ female mice undergoing daily CR. Our findings show that MDSC injection impeded CR-mediated protection against tumor growth without increasing lung metastatic burden. Overall, these results reveal that CR can slow cancer progression by affecting immune suppressive cells.Impact statement: Inoculation of MDSCs from donor mice effectively impedes the ability of calorie restriction to protect against primary tumor growth without impacting lung metastatic burden in recipient animals.
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Células Supressoras Mieloides , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Camundongos , Animais , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Restrição Calórica , Modelos Animais de Doenças , Linhagem Celular TumoralRESUMO
The structure of pili from the archaeon Methanococcus maripaludis is unlike that of any bacterial pili. However, genetic analysis of the genes involved in the formation of these pili has been lacking until this study. Pili were isolated from a nonflagellated (ΔflaK) mutant and shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to consist primarily of subunits with an apparent molecular mass of 17 kDa. In-frame deletions were created in three genes, MMP0233, MMP0236, and MMP0237, which encode proteins with bacterial type IV pilin-like signal peptides previously identified by in silico methodology as likely candidates for pilus structural proteins. Deletion of MMP0236 or MMP0237 resulted in mutant cells completely devoid of pili on the cell surface, while deletion of the third pilin-like gene, MMP0233, resulted in cells greatly reduced in the number of pili on the surface. Complementation with the deleted gene in each case returned the cells to a piliated state. Surprisingly, mass spectrometry analysis of purified pili identified the major structural pilin as another type IV pilin-like protein, MMP1685, whose gene is located outside the first pilus locus. This protein was found to be glycosylated with an N-linked branched pentasaccharide glycan. Deletion and complementation analysis confirmed that MMP1685 is required for piliation.
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Proteínas Arqueais/genética , Proteínas de Fímbrias/genética , Fímbrias Bacterianas/genética , Mathanococcus/química , Mathanococcus/genética , Sequência de Aminoácidos , Proteínas Arqueais/análise , Proteínas Arqueais/metabolismo , Proteínas de Fímbrias/análise , Proteínas de Fímbrias/metabolismo , Fímbrias Bacterianas/química , Fímbrias Bacterianas/metabolismo , Espectrometria de Massas , Mathanococcus/metabolismo , Dados de Sequência MolecularRESUMO
Cancer incidence increases with age and is a leading cause of death. Caloric restriction (CR) confers benefits on health and survival and delays cancer. However, due to CR's stringency, dietary alternatives offering the same cancer protection have become increasingly attractive. Short cycles of a plant-based diet designed to mimic fasting (FMD) are protective against tumorigenesis without the chronic restriction of calories. Yet, it is unclear whether the fasting time, level of dietary restriction, or nutrient composition is the primary driver behind cancer protection. Using a breast cancer model in mice, we compare the potency of daily CR to that of periodic caloric cycling on FMD or an isocaloric standard laboratory chow against primary tumor growth and metastatic burden. Here, we report that daily CR provides greater protection against tumor growth and metastasis to the lung, which may be in part due to the unique immune signature observed with daily CR.
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Restrição Calórica/métodos , Neoplasias Pulmonares/prevenção & controle , Neoplasias Mamárias Experimentais/dietoterapia , Animais , Linhagem Celular Tumoral , Jejum , Feminino , Neoplasias Pulmonares/secundário , Neoplasias Mamárias Experimentais/imunologia , Neoplasias Mamárias Experimentais/patologia , Camundongos , Carga Tumoral , Microambiente Tumoral/imunologiaRESUMO
Bowel preparation with low-residue diet (LRD) has resulted in higher patient satisfaction and similar polyp detection rates compared to conventional clear liquid diet. However, there is limited experience with LRD in veterans, in whom conditions associated with poor bowel preparation are more prevalent than the general population. To examine risk factors associated with inadequate bowel preparation, we conducted a chart review of outpatient colonoscopies at the Manhattan VA Medical Center from February 2017 to April 2018. To examine patient satisfaction and compliance, we administered an anonymous questionnaire to patients undergoing outpatient colonoscopy from March to August 2018. Patients assessed by chart review (n = 660) were 92% male with a mean age of 64 years. An adequate Boston Bowel Preparation Scale score ≥2 in each colonic segment was achieved in 94% of procedures. Higher BMI, diabetes, prior inadequate bowel preparation, bowel preparation duration of two days, and opioid use were associated with inadequate bowel preparation on univariable analysis. On multiple logistic regression, only higher BMI remained a predictor, with every one-unit increase associated with a 6% increased odds of poor bowel preparation. Questionnaire responses showed 84% of patients were willing to repeat LRD bowel preparation, 85% found the process easy or acceptable, and 78% reported full adherence to LRD. These findings demonstrate that bowel preparation quality, patient satisfaction, and compliance were all high among veterans using LRD.
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Colonoscopia/métodos , Dieta , Cooperação do Paciente , Satisfação do Paciente , Idoso , Assistência Ambulatorial , Catárticos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Fatores de Risco , Inquéritos e Questionários , Estados Unidos , United States Department of Veterans Affairs , VeteranosRESUMO
Citrobacter freundii AMC0703 was isolated from the intestinal mucosa of an 11-year-old organ donor. Genome analysis revealed the presence of multiple factors potentially aiding in pathogenicity, including fimbriae, flagella, and genes encoding resistance to fluoroquinolones, cephamycin, fosfomycin, and aminocoumarin.
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Eubacterium callanderi AMC0717 was isolated from the mucosa of the transverse colon of an 11-year-old organ donor. This strain contains genes putatively encoding short-chain fatty acids (SCFAs), exopolysaccharide (EPS), and several B vitamins.
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In Archaea, the preflagellin peptidase (a type IV prepilin-like peptidase designated FlaK in Methanococcus voltae and Methanococcus maripaludis) is the enzyme that cleaves the N-terminal signal peptide from preflagellins. In methanogens and several other archaeal species, the typical flagellin signal peptide length is 11 to 12 amino acids, while in other archaea preflagellins possess extremely short signal peptides. A systematic approach to address the signal peptide length requirement for preflagellin processing is presented in this study. M. voltae preflagellin FlaB2 proteins with signal peptides 3 to 12 amino acids in length were generated and used as a substrate in an in vitro assay utilizing M. voltae membranes as an enzyme source. Processing by FlaK was observed in FlaB2 proteins containing signal peptides shortened to 5 amino acids; signal peptides 4 or 3 amino acids in length were unprocessed. In the case of Sulfolobus solfataricus, where the preflagellin peptidase PibD has broader substrate specificity, some predicted substrates have predicted signal peptides as short as 3 amino acids. Interestingly, the shorter signal peptides of the various mutant FlaB2 proteins not processed by FlaK were processed by PibD, suggesting that some archaeal preflagellin peptidases are likely adapted toward cleaving shorter signal peptides. The functional complementation of signal peptidase activity by FlaK and PibD in an M. maripaludis DeltaflaK mutant indicated that processing of preflagellins was detected by complementation with either FlaK or PibD, yet only FlaK-complemented cells were flagellated. This suggested that a block in an assembly step subsequent to signal peptide removal occurred in the PibD complementation.
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Proteínas Arqueais/metabolismo , Regulação da Expressão Gênica em Archaea/fisiologia , Mathanococcus/metabolismo , Peptídeo Hidrolases/metabolismo , Sequência de Aminoácidos , Proteínas Arqueais/química , Proteínas Arqueais/genética , Regulação da Expressão Gênica/fisiologia , Mathanococcus/genética , Mutagênese Sítio-Dirigida , Mutação , Peptídeo Hidrolases/genética , Sinais Direcionadores de ProteínasRESUMO
Glycosylation is a posttranslational modification utilized in all three domains of life. Compared to eukaryotic and bacterial systems, knowledge of the archaeal processes involved in glycosylation is limited. Recently, Methanococcus voltae flagellin proteins were found to have an N-linked trisaccharide necessary for proper flagellum assembly. Current analysis by mass spectrometry of Methanococcus maripaludis flagellin proteins also indicated the attachment of an N-glycan containing acetylated sugars. To identify genes involved in sugar biosynthesis in M. maripaludis, a putative acetyltransferase was targeted for in-frame deletion. Deletion of this gene (MMP0350) resulted in a flagellin molecular mass shift to a size comparable to that expected for underglycosylated or completely nonglycoslyated flagellins, as determined by immunoblotting. Assembled flagellar filaments were not observed by electron microscopy. Interestingly, the deletion also resulted in defective pilus anchoring. Mutant cells with a deletion of MMP0350 had very few, if any, pili attached to the cell surface compared to a nonflagellated but piliated strain. However, pili were obtained from culture supernatants of this strain, indicating that the defect was not in pilus assembly but in stable attachment to the cell surface. Complementation of MMP0350 on a plasmid restored pilus attachment, but it was unable to restore flagellation, likely because the mutant ceased to make detectable flagellin. These findings represent the first report of a biosynthetic gene involved in flagellin glycosylation in archaea. Also, it is the first gene to be associated with pili, linking flagellum and pilus structure and assembly through posttranslational modifications.
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Acetiltransferases/metabolismo , Flagelos/metabolismo , Genes Arqueais , Mathanococcus/enzimologia , Acetiltransferases/genética , Flagelos/ultraestrutura , Flagelina/química , Flagelina/isolamento & purificação , Deleção de Genes , Teste de Complementação Genética , Immunoblotting , Microscopia Eletrônica de Transmissão , Microscopia Imunoeletrônica , Peso MolecularRESUMO
The early-life intestinal microbiota plays a key role in shaping host immune system development. We found that a single early-life antibiotic course (1PAT) accelerated type 1 diabetes (T1D) development in male NOD mice. The single course had deep and persistent effects on the intestinal microbiome, leading to altered cecal, hepatic, and serum metabolites. The exposure elicited sex-specific effects on chromatin states in the ileum and liver and perturbed ileal gene expression, altering normal maturational patterns. The global signature changes included specific genes controlling both innate and adaptive immunity. Microbiome analysis revealed four taxa each that potentially protect against or accelerate T1D onset, that were linked in a network model to specific differences in ileal gene expression. This simplified animal model reveals multiple potential pathways to understand pathogenesis by which early-life gut microbiome perturbations alter a global suite of intestinal responses, contributing to the accelerated and enhanced T1D development.
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Antibacterianos/efeitos adversos , Diabetes Mellitus Tipo 1/imunologia , Microbioma Gastrointestinal/imunologia , Imunidade Inata/efeitos dos fármacos , Imunidade Adaptativa/efeitos dos fármacos , Animais , Antibacterianos/imunologia , Diabetes Mellitus Tipo 1/microbiologia , Diabetes Mellitus Tipo 1/patologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Íleo/imunologia , Íleo/microbiologia , Imunidade Inata/imunologia , Intestinos/microbiologia , Camundongos , Camundongos Endogâmicos NOD , Microbiota/efeitos dos fármacos , Microbiota/imunologiaRESUMO
The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease. Using non-obese diabetic mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures. We found that in mice receiving PAT, T1D incidence was significantly higher, and microbial community composition and structure differed compared with controls. In pre-diabetic male PAT mice, the intestinal lamina propria had lower Th17 and Treg proportions and intestinal SAA expression than in controls, suggesting key roles in transducing the altered microbiota signals. PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic mice.