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1.
Cell ; 187(17): 4554-4570.e18, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-38981480

RESUMO

Diet impacts human health, influencing body adiposity and the risk of developing cardiometabolic diseases. The gut microbiome is a key player in the diet-health axis, but while its bacterial fraction is widely studied, the role of micro-eukaryotes, including Blastocystis, is underexplored. We performed a global-scale analysis on 56,989 metagenomes and showed that human Blastocystis exhibits distinct prevalence patterns linked to geography, lifestyle, and dietary habits. Blastocystis presence defined a specific bacterial signature and was positively associated with more favorable cardiometabolic profiles and negatively with obesity (p < 1e-16) and disorders linked to altered gut ecology (p < 1e-8). In a diet intervention study involving 1,124 individuals, improvements in dietary quality were linked to weight loss and increases in Blastocystis prevalence (p = 0.003) and abundance (p < 1e-7). Our findings suggest a potentially beneficial role for Blastocystis, which may help explain personalized host responses to diet and downstream disease etiopathogenesis.


Assuntos
Blastocystis , Dieta , Microbioma Gastrointestinal , Obesidade , Humanos , Blastocystis/metabolismo , Masculino , Feminino , Infecções por Blastocystis , Adulto , Pessoa de Meia-Idade , Intestinos/parasitologia , Intestinos/microbiologia , Doenças Cardiovasculares/prevenção & controle , Metagenoma
2.
Nat Rev Genet ; 24(2): 109-124, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36198908

RESUMO

Studies of the human microbiome share both technical and conceptual similarities with genome-wide association studies and genetic epidemiology. However, the microbiome has many features that differ from genomes, such as its temporal and spatial variability, highly distinct genetic architecture and person-to-person variation. Moreover, there are various potential mechanisms by which distinct aspects of the human microbiome can relate to health outcomes. Recent advances, including next-generation sequencing and the proliferation of multi-omic data types, have enabled the exploration of the mechanisms that connect microbial communities to human health. Here, we review the ways in which features of the microbiome at various body sites can influence health outcomes, and we describe emerging opportunities and future directions for advanced microbiome epidemiology.


Assuntos
Estudo de Associação Genômica Ampla , Microbiota , Humanos , Microbiota/genética , Sequenciamento de Nucleotídeos em Larga Escala
3.
Gastroenterology ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39117122

RESUMO

BACKGROUND & AIMS: Epidemiologic evidence for dietary influence on colorectal cancer (CRC) risk through the gut microbiome remains limited. METHODS: Leveraging 307 men and 212 women with stool metagenomes and dietary data, we characterized and validated a sex-specific dietary pattern associated with the CRC-related gut microbial signature (CRC Microbial Dietary Score [CMDS]). We evaluated the associations of CMDS with CRC risk according to Fusobacterium nucleatum, pks+Escherichia coli, and enterotoxigenic Bacteroides fragilis status in tumor tissue using Cox proportional hazards regression in the Health Professionals Follow-Up Study (1986-2018), Nurses' Health Study (1984-2020), and Nurses' Health Study II (1991-2019). RESULTS: The CMDS was characterized by high industrially processed food and low unprocessed fiber-rich food intakes. In 259,200 participants, we documented 3854 incident CRC cases over 6,467,378 person-years of follow-up. CMDS was associated with a higher risk of CRC (Ptrend < .001), with a multivariable hazard ratio (HRQ5 vs Q1) of 1.25 (95% CI, 1.13-1.39). The association remained after adjusting for previously established dietary patterns, for example, the Western and prudent diets. Notably, the association was stronger for tumoral F nucleatum-positive (HRQ5 vs Q1, 2.51; 95% CI, 1.68-3.75; Ptrend < .001; Pheterogeneity = .03, positivity vs negativity), pks+E coli-positive (HRQ5 vs Q1, 1.68; 95% CI, 0.84-3.38; Ptrend = .005; Pheterogeneity = .01, positivity vs negativity), and enterotoxigenic Bacteroides fragilis-positive CRC (HRQ5 vs Q1, 2.06; 95% CI, 1.10-3.88; Ptrend = .016; Pheterogeneity = .06, positivity vs negativity), compared with their negative counterparts. CONCLUSIONS: CMDS was associated with increased CRC risk, especially for tumors with detectable F nucleatum, pks+E coli, and enterotoxigenic Bacteroides fragilis in tissue. Our findings support a potential role of the gut microbiome underlying the dietary effects on CRC.

4.
Am J Gastroenterol ; 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39364876

RESUMO

INTRODUCTION: Gallstone diseases affect intestinal inflammation, bile flow, and gut microbiota, which in turn may increase the risk of inflammatory bowel disease (IBD). However, epidemiological studies exploring the associations between gallstone diseases and subsequent IBD risk have been limited. METHODS: This is a combined analysis of 3 prospective cohort studies (Nurses' Health Study, Nurses' Health Study II, and UK Biobank) and replicated in a case-control study (Chinese IBD Etiology Study). We evaluated the hazard ratios (HRs)/odds ratios (ORs) between gallstone diseases with IBD risk by Cox logistic regression or conditional logistic regression, adjusting for demographic characteristics, lifestyles, comorbidities, and medication usage. RESULTS: We identified 3,480 cases of IBD over 2,127,471 person-years of follow-up in the 3 cohort studies. The participants with gallstone disease had a 38% increase in the risk of IBD (HR 1.38, 95% confidence intervals [CI] 1.21-1.59), 68% increase in Crohn's disease (HR 1.68, 95% CI 1.38-2.06), and 24% increase in ulcerative colitis (HR 1.24, 95% CI 1.03-1.49). In Chinese IBD Etiology Study, we found even larger magnitude of effects between gallstone diseases and IBD risk (IBD: OR 3.03, 95% CI 2.32-3.97; Crohn's disease: OR 5.31; 95% CI 3.71-7.60; ulcerative colitis: OR 1.49; 95% CI 1.07-2.06). There were no major differences in the estimated associations between the presence of unremoved gallstones and prior cholecystectomy with IBD risk. DISCUSSION: Gallstone disease was linked to an increased risk of IBD and its subtypes, independent of traditional risk factors. Further research is needed to confirm these associations and clarify the underlying biological mechanisms.

5.
Opt Express ; 32(8): 13467-13477, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859316

RESUMO

We present an advanced online digital signal processing (DSP) method for correcting the phase and amplitude distortions caused by the phase modulation of the pump source and its interaction with the dispersive fibre channel in transmission systems using cascaded fibre-optical parametric amplifiers. The proposed algorithm is numerically demonstrated to achieve significant (up to 3.7 dB for a four-tone pump-phase modulation scheme) Q2-factor performance improvement over conventional DSP in 16 quadrature-amplitude modulation signal transmission.

6.
Gastroenterology ; 163(4): 852-861.e2, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35788344

RESUMO

BACKGROUND & AIMS: The use of proton pump inhibitors (PPIs) has increased rapidly in the past 2 decades. Concerns about the regular use of PPIs contributing to mortality have been raised. METHODS: We conducted a prospective cohort study using data collected from the Nurses' Health Study (2004-2018) and the Health Professionals Follow-up Study (2004-2018). Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for mortality according to PPI use. We used a modified lag-time approach to minimize reverse causation (ie, protopathic bias). RESULTS: Among 50,156 women and 21,731 men followed for 831,407 person-years and a median of 13.8 years, we documented 22,125 deaths, including 4592 deaths from cancer, 5404 from cardiovascular diseases, and 12,129 deaths from other causes. Compared with nonusers of PPIs, PPI users had significantly higher risks of all-cause mortality (HR, 1.19; 95% CI, 1.13-1.24) and mortality due to cancer (HR, 1.30; 95% CI, 1.17-1.44), cardiovascular diseases (HR, 1.13; 95% CI, 1.02-1.26), respiratory diseases (HR, 1.32; 95% CI, 1.12-1.56), and digestive diseases (HR, 1.50; 95% CI, 1.10-2.05). Upon applying lag times of up to 6 years, the associations were attenuated and no longer statistically significant (all-cause: HR, 1.04; 95% CI, 0.97-1.11; cancer: HR, 1.07; 95% CI, 0.89-1.28; cardiovascular diseases: HR, 0.94; 95% CI, 0.81-1.10; respiratory diseases: HR, 1.20; 95% CI, 0.95-1.50; digestive diseases: HR, 1.38; 95% CI, 0.88-2.18). Longer duration of PPI use did not confer higher risks for all-cause and cause-specific mortality. CONCLUSIONS: After accounting for protopathic bias, PPI use was not associated with higher risks of all-cause mortality and mortality due to major causes.


Assuntos
Doenças Cardiovasculares , Inibidores da Bomba de Prótons , Causas de Morte , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Fatores de Risco
7.
Expert Syst Appl ; 213: 119212, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36407848

RESUMO

COVID-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This deadly virus has spread worldwide, leading to a global pandemic since March 2020. A recent variant of SARS-CoV-2 named Delta is intractably contagious and responsible for more than four million deaths globally. Therefore, developing an efficient self-testing service for SARS-CoV-2 at home is vital. In this study, a two-stage vision-based framework, namely Fruit-CoV, is introduced for detecting SARS-CoV-2 infections through recorded cough sounds. Specifically, audio signals are converted into Log-Mel spectrograms, and the EfficientNet-V2 network is used to extract their visual features in the first stage. In the second stage, 14 convolutional layers extracted from the large-scale Pretrained Audio Neural Networks for audio pattern recognition (PANNs) and the Wavegram-Log-Mel-CNN are employed to aggregate feature representations of the Log-Mel spectrograms and the waveform. Finally, the combined features are used to train a binary classifier. In this study, a dataset provided by the AICovidVN 115M Challenge is employed for evaluation. It includes 7,371 recorded cough sounds collected throughout Vietnam, India, and Switzerland. Experimental results indicate that the proposed model achieves an Area Under the Receiver Operating Characteristic Curve (AUC) score of 92.8% and ranks first on the final leaderboard of the AICovidVN 115M Challenge. Our code is publicly available.

8.
Gastroenterology ; 161(6): 1842-1852.e10, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34389338

RESUMO

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) have a major impact on gut microbiome and immune function, which in turn, may increase the risk of inflammatory bowel disease (IBD). Our aim in this study was to evaluate PPI use and subsequent risk of IBD and subtypes (ie, Crohn's disease and ulcerative colitis). METHODS: This was a pooled analysis of the Nurses' Health Study (NHS, n = 82,869), NHS II (n = 95,141), and UK Biobank (n = 469,397). We included participants with information on personal use of PPIs and free of IBD or cancer at baseline. We evaluated hazard ratios and 95% confidence intervals (CIs) with Cox regression adjusting for lifestyle factors, PPI indications, comorbidities, and other medications. RESULTS: We documented 271 cases of IBD (median follow-up, 12 years) in the pooled NHS cohorts and 1419 cases (median follow-up, 8.1 years) in the UK Biobank. For both pooled NHS cohorts and UK Biobank, regular use of PPIs consistently showed a significantly positive association with IBD, Crohn's disease, and ulcerative colitis risk. Combined analyses of 3 cohorts showed that regular PPI users had an increased risk of IBD as compared with nonusers (hazard ratio, 1.42; 95% CI, 1.22-1.65; number needed to harm, 3770; 95% CI, 3668-4369). Direct comparison with H2 receptor antagonist, a less potent acid suppressor, showed that PPI use was also associated with higher IBD risk (hazard ratio, 1.38; 95% CI, 1.16-1.65). CONCLUSIONS: Regular use of PPIs was associated with an increased risk of IBD and its subtypes. The findings should be interpreted with caution because the absolute risk was low and the clinical benefits of PPIs are substantial.


Assuntos
Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Adulto , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Colite Ulcerativa/microbiologia , Doença de Crohn/diagnóstico , Doença de Crohn/imunologia , Doença de Crohn/microbiologia , Disbiose , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Reino Unido/epidemiologia , Estados Unidos/epidemiologia
9.
Clin Gastroenterol Hepatol ; 20(2): 325-333.e5, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33418133

RESUMO

OBJECTIVE: The etiology of diverticulitis is poorly understood. The long-held belief that constipation and low-fiber diet are risk factors for diverticulosis has recently been challenged by studies that suggest that more frequent bowel movements predispose to diverticulosis. We aim to prospectively explore the association between bowel movement frequency and incident diverticulitis. DESIGN: We studied participants of the Nurses' Health Study (NHS) and Health Professional Follow-up Study (HPFS). Participants' medical history, lifestyle factors and diet were used in Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios(HRs) and 95% confidence intervals(CI). RESULTS: In the NHS during over 24 years of follow-up encompassing 1,299,922 person-years, we documented 5,214 incident cases of diverticulitis, and in the HPFS over 14 years encompassing 368,661 person-years of follow-up, we documented 390 incident cases of diverticulitis. We observed an inverse association between the frequency of bowel movements and risk of diverticulitis. In the NHS, compared with women who had daily bowel movements, those with more than once daily bowel movements had a HR of 1.30 (95% CI, 1.19, 1.42) and those with less frequent bowel movements had a HR of 0.89 (95% CI, 0.82, 0.95; p-trend < 0.0001). In the HPFS, the corresponding HRs were 1.29 (95% CI, 1.04, 1.59) and 0.61 (95% CI, 0.36, 1.03; p-trend = 0.003). The association between bowel movements and diverticulitis was not modified by categories of age, BMI, physical activity, laxative use or fiber intake. CONCLUSION: More frequent bowel movements appear to be a risk factor for subsequent diverticulitis both in men and women. Further studies are needed to understand the potential mechanisms that may underlie this association.


Assuntos
Defecação , Diverticulite , Constipação Intestinal/epidemiologia , Constipação Intestinal/etiologia , Diverticulite/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco
10.
Gastroenterology ; 161(5): 1423-1432.e4, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34273347

RESUMO

BACKGROUND & AIMS: Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (H2S), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking. METHODS: We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses' Health Study II (1991-2015), a prospective cohort study with dietary assessment every 4 years through validated food frequency questionnaires and an assessment of dietary intake during adolescence in 1998. The sulfur microbial diet was characterized by intake high in processed meats, foods previously linked to CRC development, and low in mixed vegetables and legumes. Multivariable logistic regression for clustered data was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We documented 2911 cases of early-onset adenoma. After adjusting for established risk factors, higher sulfur microbial diet scores were associated with increased risk for early-onset adenomas (ORquartile [Q]4 vs Q1, 1.31; 95% CI, 1.10-1.56, Ptrend = .02), but not serrated lesions. Compared with the lowest, women in the highest quartile of sulfur microbial diet scores had significantly increased risk of early-onset adenomas with greater malignant potential (ORQ4 vs Q1, 1.65 for villous/tubulovillous histology; 95% CI, 1.12-2.43; Ptrend = .04). Similar trends for early-onset adenoma were observed based on diet consumed during adolescence. In contrast, no clear association for adenomas was identified after age 50. CONCLUSIONS: Our findings in a cohort of young women support a role for dietary interactions with gut sulfur-metabolizing bacteria in early-onset colorectal carcinogenesis, possibly beginning in adolescence.


Assuntos
Pólipos Adenomatosos/epidemiologia , Bactérias/metabolismo , Pólipos do Colo/epidemiologia , Neoplasias Colorretais/epidemiologia , Dieta/efeitos adversos , Microbioma Gastrointestinal , Lesões Pré-Cancerosas/epidemiologia , Compostos de Enxofre/efeitos adversos , Pólipos Adenomatosos/diagnóstico , Adulto , Idade de Início , Pólipos do Colo/diagnóstico , Neoplasias Colorretais/diagnóstico , Feminino , Humanos , Sulfeto de Hidrogênio/efeitos adversos , Sulfeto de Hidrogênio/metabolismo , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/diagnóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Compostos de Enxofre/administração & dosagem , Compostos de Enxofre/metabolismo , Fatores de Tempo , Estados Unidos/epidemiologia
11.
PLoS Comput Biol ; 17(11): e1009442, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34784344

RESUMO

It is challenging to associate features such as human health outcomes, diet, environmental conditions, or other metadata to microbial community measurements, due in part to their quantitative properties. Microbiome multi-omics are typically noisy, sparse (zero-inflated), high-dimensional, extremely non-normal, and often in the form of count or compositional measurements. Here we introduce an optimized combination of novel and established methodology to assess multivariable association of microbial community features with complex metadata in population-scale observational studies. Our approach, MaAsLin 2 (Microbiome Multivariable Associations with Linear Models), uses generalized linear and mixed models to accommodate a wide variety of modern epidemiological studies, including cross-sectional and longitudinal designs, as well as a variety of data types (e.g., counts and relative abundances) with or without covariates and repeated measurements. To construct this method, we conducted a large-scale evaluation of a broad range of scenarios under which straightforward identification of meta-omics associations can be challenging. These simulation studies reveal that MaAsLin 2's linear model preserves statistical power in the presence of repeated measures and multiple covariates, while accounting for the nuances of meta-omics features and controlling false discovery. We also applied MaAsLin 2 to a microbial multi-omics dataset from the Integrative Human Microbiome (HMP2) project which, in addition to reproducing established results, revealed a unique, integrated landscape of inflammatory bowel diseases (IBD) across multiple time points and omics profiles.


Assuntos
Biologia Computacional , Microbioma Gastrointestinal , Análise Multivariada , Simulação por Computador , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia
12.
Gut ; 70(6): 1070-1077, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32989021

RESUMO

OBJECTIVE: The association between the regular use of proton pump inhibitors (PPIs) and the risk of type 2 diabetes remains unclear, although a recent randomised controlled trial showed a trend towards increased risk. This study was undertaken to evaluate the regular use of PPIs and risk of type 2 diabetes. METHOD: This is a prospective analysis of 204 689 participants free of diabetes in the Nurses' Health Study (NHS), NHS II and Health Professionals Follow-up Study (HPFS). Type 2 diabetes was confirmed using American Diabetes Association (ADA) diagnostic criteria. We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, the presence of comorbidities, use of other medications and clinical indications. RESULTS: We documented 10 105 incident cases of diabetes over 2 127 471 person-years of follow-up. Regular PPI users had a 24% higher risk of diabetes than non-users (HR 1.24, 95% CI 1.17 to 1.31). The risk of diabetes increased with duration of PPI use. Fully adjusted HRs were 1.05 (95% CI 0.93 to 1.19) for participants who used PPIs for >0-2 years and 1.26 (95% CI 1.18 to 1.35) for participants who used PPIs for >2 years compared with non-users. CONCLUSIONS: Regular use of PPIs was associated with a higher risk of type 2 diabetes and the risk increased with longer duration of use. Physicians should therefore exercise caution when prescribing PPIs, particularly for long-term use.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Inquéritos Epidemiológicos , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
13.
Gut ; 70(11): 2096-2104, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34489306

RESUMO

OBJECTIVE: Poor metabolic health and unhealthy lifestyle factors have been associated with risk and severity of COVID-19, but data for diet are lacking. We aimed to investigate the association of diet quality with risk and severity of COVID-19 and its interaction with socioeconomic deprivation. DESIGN: We used data from 592 571 participants of the smartphone-based COVID-19 Symptom Study. Diet information was collected for the prepandemic period using a short food frequency questionnaire, and diet quality was assessed using a healthful Plant-Based Diet Score, which emphasises healthy plant foods such as fruits or vegetables. Multivariable Cox models were fitted to calculate HRs and 95% CIs for COVID-19 risk and severity defined using a validated symptom-based algorithm or hospitalisation with oxygen support, respectively. RESULTS: Over 3 886 274 person-months of follow-up, 31 815 COVID-19 cases were documented. Compared with individuals in the lowest quartile of the diet score, high diet quality was associated with lower risk of COVID-19 (HR 0.91; 95% CI 0.88 to 0.94) and severe COVID-19 (HR 0.59; 95% CI 0.47 to 0.74). The joint association of low diet quality and increased deprivation on COVID-19 risk was higher than the sum of the risk associated with each factor alone (Pinteraction=0.005). The corresponding absolute excess rate per 10 000 person/months for lowest vs highest quartile of diet score was 22.5 (95% CI 18.8 to 26.3) among persons living in areas with low deprivation and 40.8 (95% CI 31.7 to 49.8) among persons living in areas with high deprivation. CONCLUSIONS: A diet characterised by healthy plant-based foods was associated with lower risk and severity of COVID-19. This association may be particularly evident among individuals living in areas with higher socioeconomic deprivation.


Assuntos
COVID-19/etiologia , Dieta/efeitos adversos , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Inquéritos sobre Dietas , Dieta Saudável , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto Jovem
14.
Oncologist ; 26(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32845538

RESUMO

Individuals with cancer may be at high risk for coronavirus disease 2019 (COVID-19) and adverse outcomes. However, evidence from large population-based studies examining whether cancer and cancer-related therapy exacerbates the risk of COVID-19 infection is still limited. Data were collected from the COVID Symptom Study smartphone application since March 29 through May 8, 2020. Among 23,266 participants with cancer and 1,784,293 without cancer, we documented 10,404 reports of a positive COVID-19 test. Compared with participants without cancer, those living with cancer had a 60% increased risk of a positive COVID-19 test. Among patients with cancer, current treatment with chemotherapy or immunotherapy was associated with a 2.2-fold increased risk of a positive test. The association between cancer and COVID-19 infection was stronger among participants >65 years and males. Future studies are needed to identify subgroups by tumor types and treatment regimens who are particularly at risk for COVID-19 infection and adverse outcomes.


Assuntos
Antineoplásicos/efeitos adversos , Teste para COVID-19/estatística & dados numéricos , COVID-19/epidemiologia , Neoplasias/epidemiologia , SARS-CoV-2/isolamento & purificação , Adulto , Fatores Etários , Idoso , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/imunologia , Fatores Sexuais , Inquéritos e Questionários/estatística & dados numéricos , Adulto Jovem
15.
Gastroenterology ; 158(2): 291-302, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31622622

RESUMO

Colorectal cancer is a heterogeneous disease that develops via stepwise accumulation of well-characterized genetic and epigenetic alterations. We review the genetic changes associated with the development of precancerous colorectal adenomas and their progression to tumors, as well as the effects of defective DNA repair, chromosome instability, microsatellite instability, and alterations in the serrated pathway and DNA methylation. We provide insights into the different molecular subgroups of colorectal tumors that develop via each of these different mechanisms and their associations with patient outcomes.


Assuntos
Adenoma/genética , Carcinogênese/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Adenoma/mortalidade , Adenoma/patologia , Carcinogênese/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Metilação de DNA , Progressão da Doença , Epigênese Genética , Humanos , Instabilidade de Microssatélites , Mutação
16.
Clin Gastroenterol Hepatol ; 19(7): 1426-1435.e6, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32454258

RESUMO

BACKGROUND & AIMS: Use of antibiotics affects the composition of the microbiome and might affect development of colorectal polyps, which are precursors to colorectal cancer. METHODS: We performed a nested case-control study in Sweden of 45,744 patients with a colorectal polyp (cases) in the nationwide gastrointestinal ESPRESSO histopathology cohort, using unaffected full siblings as controls (n = 93,307). Polyps were classified by morphology SnoMed codes into conventional adenomas and serrated polyps. Through linkage to the Prescribed Drug Register, we assessed use and cumulative dispensations of antibiotic until 1 year prior to polyp diagnosis for cases and their sibling controls. RESULTS: During a median study period of 6.9 years, compared with non-users, users of antibiotics (including 28,884 cases [63.1%] and 53,222 sibling controls [57.0%]) had a higher risk of colorectal polyps (odds ratio [OR], 1.08; 95% CI, 1.04-1.13). Risk increased with higher number of dispensations (OR for ≥ 6 dispensations, 1.33; 95% CI, 1.25-1.43) (Ptrend < .0001). We observed a stronger association with polyps for broad-spectrum antibiotics (OR comparing users to non-users, 1.23; 95% CI, 1.18-1.29) than for narrow-spectrum antibiotics (OR, 1.05; 95% CI, 1.01-1.10), and for tetracyclines and quinolones (OR, 1.21) than penicillin and other classes (ORs ranged from 1.04 to 1.16). The findings remained robust with several sensitivity analyses, including use of a 2-year lead-in period for antibiotic assessment and correction for misclassification in controls. Use of broad-spectrum antibiotics was more strongly associated with risk of serrated polyps (OR, 1.29; 95% CI, 1.21-1.38) compared with risk of conventional adenomas (OR, 1.17; 95% CI, 1.11-1.24). We found no differences in risk of colon vs rectal polyps with antibiotic use (Pheterogeneity > .10). We found stronger associations for younger (<50 years) vs older adults (≥50 years) for users of quinolones, sulfonamides, trimethoprim, and cephalosporins (Pinteraction < .001). CONCLUSIONS: In a nationwide case-control study in Sweden, after accounting for hereditary and early life environmental factors, antibiotic use was associated with increased risk of colorectal polyps. Our findings indicate a role for intestinal dysbiosis in early stages of colorectal carcinogenesis.


Assuntos
Adenoma , Pólipos do Colo , Neoplasias Colorretais , Idoso , Antibacterianos/efeitos adversos , Estudos de Casos e Controles , Pólipos do Colo/epidemiologia , Colonoscopia , Neoplasias Colorretais/epidemiologia , Humanos , Fatores de Risco
17.
Gastroenterology ; 158(5): 1313-1325, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31972239

RESUMO

BACKGROUND & AIMS: Sulfur-metabolizing microbes, which convert dietary sources of sulfur into genotoxic hydrogen sulfide (H2S), have been associated with development of colorectal cancer (CRC). We identified a dietary pattern associated with sulfur-metabolizing bacteria in stool and then investigated its association with risk of incident CRC using data from a large prospective study of men. METHODS: We collected data from 51,529 men enrolled in the Health Professionals Follow-up Study since 1986 to determine the association between sulfur-metabolizing bacteria in stool and risk of CRC over 26 years of follow-up. First, in a subcohort of 307 healthy men, we profiled serial stool metagenomes and metatranscriptomes and assessed diet using semiquantitative food frequency questionnaires to identify food groups associated with 43 bacterial species involved in sulfur metabolism. We used these data to develop a sulfur microbial dietary score. We then used Cox proportional hazards modeling to evaluate adherence to this pattern among eligible individuals (n = 48,246) from 1986 through 2012 with risk for incident CRC. RESULTS: Foods associated with higher sulfur microbial diet scores included increased consumption of processed meats and low-calorie drinks and lower consumption of vegetables and legumes. Increased sulfur microbial diet scores were associated with risk of distal colon and rectal cancers, after adjusting for other risk factors (multivariable relative risk, highest vs lowest quartile, 1.43; 95% confidence interval 1.14-1.81; P-trend = .002). In contrast, sulfur microbial diet scores were not associated with risk of proximal colon cancer (multivariable relative risk 0.86; 95% CI 0.65-1.14; P-trend = .31). CONCLUSIONS: In an analysis of participants in the Health Professionals Follow-up Study, we found that long-term adherence to a dietary pattern associated with sulfur-metabolizing bacteria in stool was associated with an increased risk of distal CRC. Further studies are needed to determine how sulfur-metabolizing bacteria might contribute to CRC pathogenesis.


Assuntos
Bactérias/metabolismo , Neoplasias Colorretais/epidemiologia , Fezes/microbiologia , Comportamento Alimentar/fisiologia , Microbioma Gastrointestinal/fisiologia , Idoso , Bactérias/isolamento & purificação , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/prevenção & controle , Inquéritos sobre Dietas/estatística & dados numéricos , Seguimentos , Pessoal de Saúde/estatística & dados numéricos , Humanos , Incidência , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Enxofre/metabolismo
18.
J Neurol Neurosurg Psychiatry ; 92(12): 1254-1258, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34583944

RESUMO

BACKGROUND: Mental health issues have been reported after SARS-CoV-2 infection. However, comparison to prevalence in uninfected individuals and contribution from common risk factors (eg, obesity and comorbidities) have not been examined. We identified how COVID-19 relates to mental health in the large community-based COVID Symptom Study. METHODS: We assessed anxiety and depression symptoms using two validated questionnaires in 413148 individuals between February and April 2021; 26998 had tested positive for SARS-CoV-2. We adjusted for physical and mental prepandemic comorbidities, body mass index (BMI), age and sex. FINDINGS: Overall, 26.4% of participants met screening criteria for general anxiety and depression. Anxiety and depression were slightly more prevalent in previously SARS-CoV-2-positive (30.4%) vs SARS-CoV-2-negative (26.1%) individuals. This association was small compared with the effect of an unhealthy BMI and the presence of other comorbidities, and not evident in younger participants (≤40 years). Findings were robust to multiple sensitivity analyses. Association between SARS-CoV-2 infection and anxiety and depression was stronger in individuals with recent (<30 days) versus more distant (>120 days) infection, suggesting a short-term effect. INTERPRETATION: A small association was identified between SARS-CoV-2 infection and anxiety and depression symptoms. The proportion meeting criteria for self-reported anxiety and depression disorders is only slightly higher than prepandemic.


Assuntos
Ansiedade/epidemiologia , COVID-19/psicologia , Depressão/epidemiologia , Aplicativos Móveis , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Prevalência , SARS-CoV-2 , Autorrelato , Adulto Jovem
19.
Gastroenterology ; 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39307254
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