RESUMO
The incidence of pediatric inflammatory bowel disease (IBD), which includes Crohn disease and ulcerative colitis, has risen alarmingly in the Western and developing world in recent decades. Epidemiologic (including monozygotic twin and migrant) studies highlight the substantial role of environment and nutrition in IBD etiology. Here we review the literature supporting the developmental and environmental origins hypothesis of IBD. We also provide a detailed exploration of how the human microbiome and epigenome (primarily through DNA methylation) may be important elements in the developmental origins of IBD in both children and adults.
Assuntos
Bactérias , Dieta , Meio Ambiente , Epigênese Genética , Genoma , Doenças Inflamatórias Intestinais/etiologia , Microbiota , Metilação de DNA , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/microbiologiaRESUMO
BACKGROUND: Advance care planning (ACP), a process of sharing one's values and preferences for future medical treatments, can improve quality of life, reduce loved ones' anxiety, and decrease unwanted medical utilization and costs. Despite benefits to patients and health care systems, ACP uptake often remains low, due partially to lack of knowledge and difficulty initiating discussions. Digital tools may help reduce these barriers to entry. METHODS: We retrospectively examined data from pilot deployment of Koda Health patient-facing ACP among Houston Methodist Coordinated Care patients, for quality improvement (QI) purposes. Patients referred by nurse navigators could access Koda's digital platform, complete ACP, and share the legal documentation generated. Analyzed measures include usage rates and ACP-related decisions within the platform. RESULTS: Of eligible patients (n = 203), 52.7% voluntarily completed their plan. Engagement and completion rates were similar across demographics. Patients indicated majority preference (66.4%) toward spending the last days of life at home. Most patients indicated wanting no life-support intervention if quality of life became unacceptable (51 to 71% across 4 treatments). Life-support decisions were similar between demographic categories, excepting CPR and dialysis, wherein a greater portion of Black patients than White patients preferred at least trial intervention, rather than none. CONCLUSIONS: As an observational QI analysis, limitations include bounded geographical reach and lack of data on ACP impacts to subsequent health care utilization, which future studies will address. Findings suggest that digital health tools like Koda can effectively facilitate equitable ACP access and may help support health systems and providers in offering comprehensive ACP.
Assuntos
Organizações de Assistência Responsáveis , Planejamento Antecipado de Cuidados , Humanos , Estudos Retrospectivos , Qualidade de VidaRESUMO
Mechanistic investigation of host-microbe interactions in the human gut are hindered by difficulty of co-culturing microbes with intestinal epithelial cells. On one hand the gut bacteria are a mix of facultative, aerotolerant or obligate anaerobes, while the intestinal epithelium requires oxygen for growth and function. Thus, a coculture system that can recreate these contrasting oxygen requirements is critical step towards our understanding microbial-host interactions in the human gut. Here, we demonstrate Intestinal Organoid Physoxic Coculture (IOPC) system, a simple and cost-effective method for coculturing anaerobic intestinal bacteria with human intestinal organoids (HIOs). Using commensal anaerobes with varying degrees of oxygen tolerance, such as nano-aerobe Bacteroides thetaiotaomicron and strict anaerobe Blautia sp., we demonstrate that IOPC can successfully support 24-48 hours HIO-microbe coculture. The IOPC recapitulates the contrasting oxygen conditions across the intestinal epithelium seen in vivo. The IOPC cultured HIOs showed increased barrier integrity, and induced expression of immunomodulatory genes. A transcriptomic analysis suggests that HIOs from different donors show differences in the magnitude of their response to coculture with anaerobic bacteria. Thus, the IOPC system provides a robust coculture setup for investigating host-microbe interactions in complex, patient-derived intestinal tissues, that can facilitate the study of mechanisms underlying the role of the microbiome in health and disease.
Assuntos
Técnicas de Cocultura , Mucosa Intestinal , Organoides , Oxigênio , Humanos , Organoides/microbiologia , Organoides/metabolismo , Oxigênio/metabolismo , Técnicas de Cocultura/métodos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/citologia , Microbioma Gastrointestinal , Interações entre Hospedeiro e Microrganismos , Bactérias Anaeróbias/crescimento & desenvolvimento , Bactérias Anaeróbias/metabolismo , Intestinos/microbiologia , Intestinos/citologia , Bacteroides thetaiotaomicron/metabolismoRESUMO
Background: Advance care planning (ACP) is a process that involves patients expressing their personal goals, values, and future medical care preferences. Digital applications may help facilitate this process, though their use in older adults has not been adequately studied. Objective: This pilot study aimed to evaluate the reach, adoption, and usability of Koda Health, a web-based patient-facing ACP platform, among older adults. Methods: Older adults (aged 50 years and older) who had an active Epic MyChart account at an academic health care system in North Carolina were recruited to participate. A total of 2850 electronic invitations were sent through MyChart accounts with an embedded hyperlink to the Koda platform. Participants who agreed to participate were asked to complete pre- and posttest surveys before and after navigating through the Koda Health platform. Primary outcomes were reach, adoption, and System Usability Scale (SUS) scores. Exploratory outcomes included ACP knowledge and readiness. Results: A total of 161 participants enrolled in the study and created an account on the platform (age: mean 63, SD 9.3 years), with 80% (129/161) of these participants going on to complete all steps of the intervention, thereby generating an advance directive. Participants reported minimal difficulty in using the Koda platform, with an overall SUS score of 76.2. Additionally, knowledge of ACP (eg, mean increase from 3.2 to 4.2 on 5-point scale; P<.001) and readiness (eg, mean increase from 2.6 to 3.2 on readiness to discuss ACP with health care provider; P<.001) significantly increased from before to after the intervention. Conclusions: This study demonstrated that the Koda Health platform is feasible, had above-average usability, and improved ACP documentation of preferences in older adults. Our findings indicate that web-based health tools like Koda may help older individuals learn about and feel more comfortable with ACP while potentially facilitating greater engagement in care planning.
Assuntos
Planejamento Antecipado de Cuidados , Estudos de Viabilidade , Humanos , Projetos Piloto , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , North Carolina , Intervenção Baseada em Internet , Internet , Inquéritos e QuestionáriosRESUMO
Background and aims: Bacteriotherapy aimed at addressing dysbiosis may be therapeutic for Inflammatory Bowel Diseases (IBDs). We sought to determine if defined Bacteroides-based bacteriotherapy could be an effective and consistent alternative to fecal microbiota transplantation (FMT) in a murine model of IBD. Methods: We induced experimental colitis in 8- 12-week-old C57BL/6 mice using 2-3% dextran sodium sulfate. Mice were simultaneously treated by oral gavage with a triple-Bacteroides cocktail, individual Bacteroides strains, FMT using stool from healthy donor mice, or their own stool as a control. Survival, weight loss and markers of inflammation (histology, serum amyloid A, cytokine production) were correlated to 16S rRNA gene profiling of fecal and mucosal microbiomes. Results: Triple-Bacteroides combination therapy was more protective against weight loss and mortality than traditional FMT therapy. B. ovatus ATCC8483 was more effective than any individual strain, or a combination of strains, in preventing weight loss, decreasing histological damage, dampening inflammatory response, and stimulating epithelial recovery. Irrespective of the treatment group, overall Bacteroides abundance associated with treatment success and decreased cytokine production while the presence of Akkermansia correlated with treatment failure. However, the therapeutic benefit associated with high Bacteroides abundance was negated in the presence of Streptococcus. Conclusions: Bacteroides ovatus monotherapy was more consistent and effective than traditional FMT at ameliorating colitis and stimulating epithelial recovery in a murine model of IBD. Given the tolerability of Bacteroides ovatus ATCC 8483 in an active, on-going human study, this therapy may be repurposed for the management of IBD in a clinically expedient timeline.
Assuntos
Bacteroides/fisiologia , Colite/terapia , Transplante de Microbiota Fecal , Animais , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Bacteroides/classificação , Bacteroides/crescimento & desenvolvimento , Colite/induzido quimicamente , Colite/patologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Fezes/microbiologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/patologia , Inflamação/prevenção & controle , Masculino , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S/genética , Análise de Sobrevida , Resultado do TratamentoRESUMO
A wide diversity of fungi have been detected in the human gastrointestinal (GI) tract with the potential to provide or influence important functions. However, many of the fungi most commonly detected in stool samples are also present in food or the oral cavity. Therefore, to recognize which gut fungi are likely to have a sustained influence on human health, there is a need to separate transient members of the GI tract from true colonizers. To identify colonizing fungi, the eukaryotic rRNA operon's second internal transcribed spacer (ITS2) was sequenced from the stool, saliva, and food of healthy adults following consumption of different controlled diets. Unlike most bacterial 16S rRNA genes, the only fungal ITS2 operational taxonomic units (OTUs) detected in stool DNA across multiple diets were also present in saliva and/or food. Additional analyses, including culture-based approaches and sequencing of the 18S rRNA gene, ITS2 cDNA, and DNA extracted using alternative methods, failed to detect additional fungi. Two abundant fungi, Saccharomyces cerevisiae and Candida albicans, were examined further in healthy volunteers. Saccharomyces became undetectable in stool when a S. cerevisiae-free diet was consumed, and the levels of C. albicans in stool were dramatically reduced by more frequent cleaning of teeth. Extremely low fungal abundance, the inability of fungi to grow under conditions mimicking the distal gut, and evidence from analysis of other public datasets further support the hypothesis that fungi do not routinely colonize the GI tracts of healthy adults. IMPORTANCE We sought to identify the fungi that colonize healthy GI tracts and that have a sustained influence on the diverse functions of the gut microbiome. Instead, we found that all fungi in the stool of healthy volunteers could be explained by their presence in oral and dietary sources and that our results, together with those from other analyses, support the model that there is little or no gastrointestinal colonization by fungi. This may be due to Westernization, primate evolution, fungal ecology, and/or the strong defenses of a healthy immune system. Importantly, fungal colonization of the GI tract may often be indicative of disease. As fungi can cause serious infections in immunocompromised individuals and are found at increased abundance in multiple disorders of the GI tract, understanding normal fungal colonization is essential for proper treatment and prevention of fungal pathogenesis.
Assuntos
Fungos/classificação , Trato Gastrointestinal/microbiologia , Micobioma/fisiologia , Adulto , Candida albicans/genética , Candida albicans/isolamento & purificação , DNA Espaçador Ribossômico/genética , Dieta , Fezes/microbiologia , Microbiologia de Alimentos , Fungos/isolamento & purificação , Trato Gastrointestinal/fisiologia , Voluntários Saudáveis , Humanos , Boca/microbiologia , RNA Ribossômico 18S/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/isolamento & purificação , Saliva/microbiologia , Análise de Sequência de DNARESUMO
The short and long-term impact of birth mode on the developing gut microbiome in neonates has potential implications for the health of infants. In term infants, the microbiome immediately following birth across multiple body sites corresponds to birth mode, with increased Bacteroides in vaginally delivered infants. We aimed to determine the impact of birth mode of the preterm gut microbiome over the first 100 days of life and following neonatal intensive care unit (NICU) discharge. In total, 867 stool samples from 46 preterm infants (21 cesarean and 25 vaginal), median gestational age 27 weeks, were sequenced (V4 region 16S rRNA gene, Illumina MiSeq). Of these, 776 samples passed quality filtering and were included in the analysis. The overall longitudinal alpha-diversity and within infant beta-diversity was comparable between cesarean and vaginally delivered infants. Vaginally delivered infants kept significantly more OTUs from 2 months of life and following NICU discharge, but OTUs lost, gained, and regained were not different based on birth mode. Furthermore, the temporal progression of dominant genera was comparable between birth modes and no significant difference was found for any genera following adjustment for covariates. Lastly, preterm gut community types (PGCTs) showed some moderate differences in very early life, but progressed toward a comparable pattern by week 5. No PGCT was significantly associated with cesarean or vaginal birth. Unlike term infants, birth mode was not significantly associated with changes in microbial diversity, composition, specific taxa, or overall microbial development in preterm infants. This may result from the dominating effects of NICU exposures including the universal use of antibiotics immediately following birth and/or the lack of Bacteroides colonizing preterm infants.