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1.
Artículo en Inglés | MEDLINE | ID: mdl-38642272

RESUMEN

PURPOSE OF REVIEW: Growing evidence supports the contribution of age in the composition and function of the gut microbiome, with specific findings associated with health in old age and longevity. RECENT FINDINGS: Current studies have associated certain microbiota, such as Butyricimonas, Akkermansia, and Odoribacter, with healthy aging and the ability to survive into extreme old age. Furthermore, emerging clinical and pre-clinical research have shown promising mechanisms for restoring a healthy microbiome in elderly populations through various interventions such as fecal microbiota transplant (FMT), dietary interventions, and exercise programs. Despite several conceptually exciting interventional studies, the field of microbiome research in the elderly remains limited. Specifically, large longitudinal studies are needed to better understand causative relationships between the microbiome and healthy aging. Additionally, individualized approaches to microbiome interventions based on patients' co-morbidities and the underlying functional capacity of their microbiomes are needed to achieve optimal results.

2.
Ann Rheum Dis ; 82(10): 1315-1327, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37365013

RESUMEN

OBJECTIVE: Whereas genetic susceptibility for systemic lupus erythematosus (SLE) has been well explored, the triggers for clinical disease flares remain elusive. To investigate relationships between microbiota community resilience and disease activity, we performed the first longitudinal analyses of lupus gut-microbiota communities. METHODS: In an observational study, taxononomic analyses, including multivariate analysis of ß-diversity, assessed time-dependent alterations in faecal communities from patients and healthy controls. From gut blooms, strains were isolated, with genomes and associated glycans analysed. RESULTS: Multivariate analyses documented that, unlike healthy controls, significant temporal community-wide ecological microbiota instability was common in SLE patients, and transient intestinal growth spikes of several pathogenic species were documented. Expansions of only the anaerobic commensal, Ruminococcus (blautia) gnavus (RG) occurred at times of high-disease activity, and were detected in almost half of patients during lupus nephritis (LN) disease flares. Whole genome sequence analysis of RG strains isolated during these flares documented 34 genes postulated to aid adaptation and expansion within a host with an inflammatory condition. Yet, the most specific feature of strains found during lupus flares was the common expression of a novel type of cell membrane-associated lipoglycan. These lipoglycans share conserved structural features documented by mass spectroscopy, and highly immunogenic repetitive antigenic-determinants, recognised by high-level serum IgG2 antibodies, that spontaneously arose, concurrent with RG blooms and lupus flares. CONCLUSIONS: Our findings rationalise how blooms of the RG pathobiont may be common drivers of clinical flares of often remitting-relapsing lupus disease, and highlight the potential pathogenic properties of specific strains isolated from active LN patients.


Asunto(s)
Microbioma Gastrointestinal , Lupus Eritematoso Sistémico , Nefritis Lúpica , Microbiota , Humanos , Microbioma Gastrointestinal/genética , Brote de los Síntomas , Heces , Nefritis Lúpica/genética
3.
J Clin Gastroenterol ; 57(10): 1024-1030, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36227005

RESUMEN

PURPOSE: Fecal microbiota transplant (FMT) is increasingly performed for Clostridioides difficile infection (CDI), although long-term efficacy and safety data are limited and are focused on results from academic medical centers rather than private settings where most patients receive care. METHODS: Medical records of 165 patients who received FMTs for CDI were reviewed from an academic medical center and an adjacent, unaffiliated private practice. Of these patients, 68 also completed a survey regarding their long-term disease course and interval health. RESULTS: CDI resolution occurred in 81.3% (100/123) at the academic center and 95.2% (40/42) in the private setting. Private practice patients were more likely to present with recurrent, rather than refractory, CDI (92.9% vs. 66.7% P <0.001). Those from the academic center were more likely to have comorbid IBD, recent hospitalization, recent proton pump inhibitor use, ongoing immunosuppression, and inpatient FMT (all P values <0.05).Among surveyed patients, 29.4% developed interval comorbidities or changes to pre-existing conditions after a median follow-up of 33.7 months (IQR 13.2 to 44.3 mo). Of 30 patients requiring subsequent antibiotics, 13.3% suffered CDI relapse. All subjects who had initially responded to FMT but had a subsequent CDI (17.9%, 10/56) responded to another FMT. CONCLUSIONS: In a real-world setting, patients who underwent FMT at academic centers differed significantly in clinical characteristics from those treated at a private practice. In both settings, FMT is an effective treatment for CDI not responding to standard therapies, even after subsequent antibiotic use. New diagnoses following FMT, however, are common and merit further exploration.

4.
Clin Auton Res ; 33(2): 87-92, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36735101

RESUMEN

OBJECTIVE: Familial dysautonomia (FD) is a rare inherited autosomal recessive disorder with abnormal somatosensory, enteric, and afferent autonomic neurons. We aimed to define the incidence of gastrointestinal bleeding and its associated risk factors in patients with FD. METHODS: In this retrospective case-control study, we identified all episodes of gastrointestinal bleeding in patients with FD, occurring over four decades (January 1980-December 2017), using the New York University FD registry. RESULTS: We identified 104 episodes of gastrointestinal bleeding occurring in 60 patients with FD. The estimated incidence rate of gastrointestinal bleeds in the FD population rate was 4.20 episodes per 1000 person-years. We compared the 60 cases with 94 age-matched controls. Bleeding in the upper gastrointestinal tract from gastric and duodenal ulcers occurred most frequently (64 bleeds, 75.6%). Patients were more likely to have a gastrostomy (G)-tube and a Nissen fundoplication [odds ratio (OR) 3.73, 95% confidence interval (CI) 1.303-13.565] than controls. The mean time from G-tube placement to first gastrointestinal bleed was 7.01 years. The mean time from Nissen fundoplication to bleed was 7.01 years. Cases and controls had similar frequency of intake of nonsteroidal antiinflammatory drugs (NSAID) and selective serotonin reuptake inhibitors (SSRI). CONCLUSION: The incidence of gastrointestinal bleeding in the pediatric FD population was estimated to be 4.20 per 1000 person-years, 21 times higher than in the general pediatric population (0.2 per 1000 person-years). Patients with FD with a G-tube and a Nissen fundoplication had a higher risk of a subsequent gastrointestinal bleeding.


Asunto(s)
Disautonomía Familiar , Humanos , Niño , Disautonomía Familiar/complicaciones , Disautonomía Familiar/epidemiología , Estudios de Casos y Controles , Estudios Retrospectivos , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/complicaciones , Inhibidores Selectivos de la Recaptación de Serotonina
5.
Gastroenterology ; 160(1): 183-192.e3, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33011173

RESUMEN

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is used commonly for treatment of Clostridioides difficile infections (CDIs), although prospective safety data are limited and real-world FMT practice and outcomes are not well described. The FMT National Registry was designed to assess FMT methods and both safety and effectiveness outcomes from North American FMT providers. METHODS: Patients undergoing FMT in clinical practices across North America were eligible. Participating investigators enter de-identified data into an online platform, including FMT protocol, baseline patient characteristics, CDI cure and recurrence, and short and long-term safety outcomes. RESULTS: Of the first 259 participants enrolled at 20 sites, 222 had completed short-term follow-up at 1 month and 123 had follow-up to 6 months; 171 (66%) were female. All FMTs were done for CDI and 249 (96%) used an unknown donor (eg, stool bank). One-month cure occurred in 200 patients (90%); of these, 197 (98%) received only 1 FMT. Among 112 patients with initial cure who were followed to 6 months, 4 (4%) had CDI recurrence. Severe symptoms reported within 1-month of FMT included diarrhea (n = 5 [2%]) and abdominal pain (n = 4 [2%]); 3 patients (1%) had hospitalizations possibly related to FMT. At 6 months, new diagnoses of irritable bowel syndrome were made in 2 patients (1%) and inflammatory bowel disease in 2 patients (1%). CONCLUSIONS: This prospective real-world study demonstrated high effectiveness of FMT for CDI with a good safety profile. Assessment of new conditions at long-term follow-up is planned as this registry grows and will be important for determining the full safety profile of FMT.


Asunto(s)
Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal , Enfermedades Inflamatorias del Intestino/terapia , Síndrome del Colon Irritable/terapia , Sistema de Registros , Adolescente , Adulto , Clostridioides difficile , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Estados Unidos , Adulto Joven
6.
Dig Dis Sci ; 66(8): 2732-2743, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-32816215

RESUMEN

BACKGROUND: Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Creatine kinase (CK) levels and CK-related adverse events (AEs) in tofacitinib-treated patients with UC were evaluated. METHODS: Data were analyzed for three UC cohorts: Induction (phase 2 and 3 induction studies); Maintenance (phase 3 maintenance study); Overall [patients who received tofacitinib 5 or 10 mg twice daily (b.d.) in phase 2, phase 3, or open-label, long-term extension studies; data at November 2017]. Clinical trial data for tofacitinib-treated patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis are presented for contextualization. RESULTS: Week 8 mean change from baseline CK with tofacitinib 10 mg b.d. induction therapy was 91.1 U/L (95% CI, 48.1-134.1) versus 19.2 U/L (8.5-29.9) with placebo. Among patients completing induction with 10 mg b.d. and re-randomized to 52 weeks of maintenance therapy, mean increases from induction baseline to the end of maintenance were 35.9 (8.1-63.7), 90.3 (51.9-128.7), and 115.6 U/L (91.6-139.7), with placebo, 5 and 10 mg b.d., respectively. The incidence rate (unique patients with events per 100 patient-years) for AEs of CK elevation in the tofacitinib-treated UC Overall cohort was 6.6 versus 2.2, 6.5, and 3.7 for tofacitinib-treated patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis, respectively. No serious AEs of CK elevation or AEs of myopathy occurred in UC studies. CONCLUSIONS: In patients with UC, CK elevations with tofacitinib appeared reversible and not associated with clinically significant AEs. UC findings were consistent with tofacitinib use in other inflammatory diseases. TRIAL REGISTRATION: NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612; NCT01262118; NCT01484561; NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01059864; NCT01164579; NCT00976599; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT00413699; NCT00661661; NCT01710046; NCT00678210; NCT01276639; NCT01309737; NCT01241591; NCT01186744; NCT01163253; NCT01877668; NCT01882439; NCT01976364.


Asunto(s)
Colitis Ulcerosa/tratamiento farmacológico , Creatina Quinasa/sangre , Piperidinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Adulto , Artritis Psoriásica/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piperidinas/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Psoriasis/tratamiento farmacológico , Pirimidinas/administración & dosificación , Factores de Riesgo
7.
Clin Auton Res ; 31(1): 109-116, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33025279

RESUMEN

PURPOSE: Familial dysautonomia (FD) is a rare hereditary sensory and autonomic neuropathy (HSAN-3) that is clinically characterized by impaired pain and temperature perception and abnormal autonomic function. Patients with FD have gastrointestinal dysmotility and report a range of gastrointestinal symptoms that have yet to be systematically evaluated. The aim of this study was to establish the frequency and severity of gastrointestinal symptoms in patients with FD. METHODS: The validated National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) survey questionnaire, together with additional FD-specific questions, were distributed to 202 living patients with genetically confirmed FD who had been identified from the New York University FD Patient Registry or, when relevant, to their respective caretaker. As a comparison group, we used a general US adult population for whom PROMIS scores were available (N = 71,812). RESULTS: Of the 202 questionnaires distributed, 77 (38%) were returned, of which 53% were completed by the patient. Median age of the respondents was 25 years, and 44% were male. Gastrostomy tube was the sole nutrition route for 25% of the patients, while 53% were reliant on the gastrostomy tube only for liquid intake. The prevalence of gastrointestinal symptoms was significantly higher in each of the eight domains of PROMIS in patients with FD than in the controls. Gastrointestinal symptoms as measured by raw scores on the PROMIS scale were significantly less severe in the FD patient group than in the control population in all domains with the exception of the abdominal pain domain. The surveys completed by caregivers reported the same burden of symptoms as those completed only by patients. CONCLUSION: Gastrointestinal symptoms affect nearly all patients with FD. Gastrointestinal symptoms are more prevalent in adult patients with FD than in the average US adult population but are less severe in the former.


Asunto(s)
Disautonomía Familiar , Enfermedades Gastrointestinales , Neuropatías Hereditarias Sensoriales y Autónomas , Adulto , Disautonomía Familiar/complicaciones , Disautonomía Familiar/epidemiología , Enfermedades Gastrointestinales/epidemiología , Humanos , Masculino , Prevalencia , Encuestas y Cuestionarios
8.
J Pediatr Gastroenterol Nutr ; 68(4): 502-508, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30540709

RESUMEN

OBJECTIVES: The gut microbiome is believed to play a role in the susceptibility to and treatment of Clostridium difficile infections (CDIs). It is, however, unknown whether the gut microbiome is also affected by asymptomatic C difficile colonization. Our study aimed to evaluate the fecal microbiome of children based on C difficile colonization, and CDI risk factors, including antibiotic use and comorbid inflammatory bowel disease (IBD). METHODS: Subjects with IBD and non-IBD controls were prospectively enrolled from pediatric clinics for a biobanking project (n = 113). A fecal sample was collected from each subject for research purposes only and was evaluated for asymptomatic toxigenic C difficile colonization. Fecal microbiome composition was determined by 16S rRNA sequencing. RESULTS: We found reduced bacterial diversity and altered microbiome composition in subjects with C difficile colonization, concurrent antibiotic use, and/or concomitant IBD (all P < 0.05). Accounting for antibiotic use and IBD status, children colonized with C difficile had significant enrichment in taxa from the genera Ruminococcus, Eggerthella, and Clostridium. Children without C difficile had increased relative abundances of Faecalibacterium and Rikenellaceae. Imputed metagenomic functions of those colonized were enriched for genes in oxidative phosphorylation and beta-lactam resistance, whereas in the subjects without C difficile, several functions in translation and metabolism were over-represented. CONCLUSIONS: In children, C difficile colonization, or factors that predispose to colonization such as antibiotic use and IBD status were associated with decreased gut bacterial diversity and altered microbiome composition. Averting such microbiome alterations may be a method to prevent or treat CDI.


Asunto(s)
Clostridioides difficile , Infecciones por Clostridium/microbiología , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino/complicaciones , Adolescente , Alabama , Baltimore , Niño , Preescolar , Heces/microbiología , Femenino , Humanos , Masculino , Estudios Prospectivos , Adulto Joven
9.
Qual Life Res ; 27(2): 273-290, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28849311

RESUMEN

PURPOSE: To conduct a systematic literature review of the reliability, construct validity, and responsiveness of the SF-36® Health Survey (SF-36) in patients with ulcerative colitis (UC). METHODS: We performed a systematic search of electronic medical databases to identify published peer-reviewed studies which reported scores from the eight scales and/or two summary measures of the SF-36 collected from adult patients with UC. Study findings relevant to reliability, construct validity, and responsiveness were reviewed. RESULTS: Data were extracted and summarized from 43 articles meeting inclusion criteria. Convergent validity was supported by findings that 83% (197/236) of correlations between SF-36 scales and measures of disease symptoms, disease activity, and functioning exceeded the prespecified threshold (r ≥ |0.40|). Known-groups validity was supported by findings of clinically meaningful differences in SF-36 scores between subgroups of patients when classified by disease activity (i.e., active versus inactive), symptom status, and comorbidity status. Responsiveness was supported by findings of clinically meaningful changes in SF-36 scores following treatment in non-comparative trials, and by meaningfully larger improvements in SF-36 scores in treatment arms relative to controls in randomized controlled trials. The sole study of SF-36 reliability found evidence supporting internal consistency (Cronbach's α ≥ 0.70) for all SF-36 scales and test-retest reliability (intraclass correlation coefficient ≥0.70) for six of eight scales. CONCLUSIONS: Evidence from this systematic literature review indicates that the SF-36 is reliable, valid, and responsive when used with UC patients, supporting the inclusion of the SF-36 as an endpoint in clinical trials for this patient population.


Asunto(s)
Colitis Ulcerosa/epidemiología , Encuestas Epidemiológicas/métodos , Psicometría/métodos , Calidad de Vida/psicología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados
11.
bioRxiv ; 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38370680

RESUMEN

Changes in the gut microbiome have been associated with several human diseases, but the molecular and functional details underlying these associations remain largely unknown. Here, we performed a multi-cohort analysis of small molecule biosynthetic gene clusters (BGCs) in 5,306 metagenomic samples of the gut microbiome from 2,033 Inflammatory Bowel Disease (IBD) patients and 833 matched healthy subjects and identified a group of Clostridia-derived BGCs that are significantly associated with IBD. Using synthetic biology, we discovered and solved the structures of six fatty acid amides as the products of the IBD-enriched BGCs. Using two mouse models of colitis, we show that the discovered small molecules disrupt gut permeability and exacerbate inflammation in chemically and genetically susceptible mice. These findings suggest that microbiome-derived small molecules may play a role in the etiology of IBD and represent a generalizable approach for discovering molecular mediators of microbiome-host interactions in the context of microbiome-associated diseases.

12.
Gastro Hep Adv ; 3(3): 326-332, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38765199

RESUMEN

BACKGROUND AND AIMS: The prevalence of inflammatory bowel disease (IBD) is increasing globally. In this context, identifying risk factors for severe disease is important. We examined how race/ethnicity and immigration status influence IBD manifestations, treatments, and outcomes in a diverse, tertiary-care safety-net hospital. METHODS: We conducted a single-center retrospective review of all IBD inpatients and outpatients treated from 1997-2017. Using logistic regression modeling, we compared disease onset, treatment, and outcomes by race (White, Black, Hispanic, or Asian) and immigration status (US-born vs foreign-born). RESULTS: A total of 577 patients were identified, of which 29.8% were White, 27.4% were Hispanic, 21.7% were Black, and 13.0% were Asian. Compared to Whites, Asians were more likely to be male (odds ratio [OR] 2.63, 95% confidence interval [CI]: 1.45, 5.00), whereas Blacks were more likely to be diagnosed with Crohn's disease (OR 1.75, 95% CI: 1.10, 2.77) and more likely to undergo IBD-related intestinal resection (OR 2.49, 95% CI: 1.40, 4.50). Compared to US-born patients, foreign-born patients were more likely to be diagnosed with ulcerative colitis (OR 1.77, 95% CI: 1.04, 3.02). They were also less likely to be diagnosed before 16 years of age (OR 0.19, 95% CI: 0.08, 0.41), to have undergone intestinal resections (OR 0.39, 95% CI: 0.19, 0.83), to have received biologics (OR 0.43, 95% CI: 0.25, 0.76), or to have had dermatologic manifestations (OR 0.12, 95% CI: 0.03, 0.41). CONCLUSION: IBD phenotype varies by race, although foreign-born patients of all races show evidence of later-onset and milder disease. These findings may aid in disease prognostication and clinical management and, furthermore, may provide insight into intrinsic and environmental influences on IBD pathogenesis.

13.
Ann Gastroenterol ; 37(2): 192-198, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38481776

RESUMEN

Background: Patients with inflammatory bowel disease (IBD) are at increased risk of anxiety and mood disorders. This study examines the temporal trends and clinical impact of anxiety and mood disorder diagnoses in hospitalized IBD patients in the United States during a 10-year period. Methods: Using the National Inpatient Sample from 2009-2018, all IBD-related discharges in adults were analyzed. Primary outcomes were the prevalence and temporal trends of mood disorder and anxiety diagnoses for IBD-related admissions. The impact of the psychiatric comorbidities on clinical outcomes was also evaluated. Results: A total of 1,718,736 IBD-related discharged were identified. A diagnosis of anxiety or a mood disorder was found to have a prevalence of 16.44% and 18.97%, respectively, amongst IBD-related admissions. The prevalence of anxiety disorders amongst hospitalized IBD patients increased significantly (from 12.13% to 20.26%), whereas the prevalence of mood disorders did not (17.46% and 18.9%). IBD admissions with psychiatric comorbidities had lower rates of IBD-related complications or mortality during hospitalization compared to IBD admissions without comorbid psychiatric diagnoses. This population, however, was more likely to experience certain comorbidities such as Clostridioides difficile, pneumonia, and venous thromboembolism, as well as a longer hospitalization. Conclusions: The prevalence of comorbid anxiety among hospitalized IBD patients in the United States matches or exceeds the prevalence of anxiety in the general hospitalized population. Given its association with more in-hospital complications and a longer hospital stay, it is important to further understand how psychological screening and mental health services can improve the management of hospitalized IBD patients.

14.
Inflamm Bowel Dis ; 30(Supplement_2): S39-S54, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38778628

RESUMEN

Precision medicine is part of 5 focus areas of the Challenges in IBD Research 2024 research document, which also includes preclinical human IBD mechanisms, environmental triggers, novel technologies, and pragmatic clinical research. Building on Challenges in IBD Research 2019, the current Challenges aims to provide a comprehensive overview of current gaps in inflammatory bowel diseases (IBDs) research and deliver actionable approaches to address them with a focus on how these gaps can lead to advancements in interception, remission, and restoration for these diseases. The document is the result of multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient-centric research prioritization. In particular, the precision medicine section is focused on the main research gaps in elucidating how to bring the best care to the individual patient in IBD. Research gaps were identified in biomarker discovery and validation for predicting disease progression and choosing the most appropriate treatment for each patient. Other gaps were identified in making the best use of existing patient biosamples and clinical data, developing new technologies to analyze large datasets, and overcoming regulatory and payer hurdles to enable clinical use of biomarkers. To address these gaps, the Workgroup suggests focusing on thoroughly validating existing candidate biomarkers, using best-in-class data generation and analysis tools, and establishing cross-disciplinary teams to tackle regulatory hurdles as early as possible. Altogether, the precision medicine group recognizes the importance of bringing basic scientific biomarker discovery and translating it into the clinic to help improve the lives of IBD patients.


Precision medicine is the practice of getting the most suitable drug or treatment option to each individual patient at the right time. In Crohn's disease and ulcerative colitis, we need to learn more about the diversity of patients to deliver precision medicine.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Medicina de Precisión , Humanos , Medicina de Precisión/métodos , Enfermedades Inflamatorias del Intestino/terapia , Biomarcadores/análisis , Investigación Biomédica
15.
Nat Rev Gastroenterol Hepatol ; 20(2): 81-100, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36258032

RESUMEN

Antibiotic use is increasing worldwide. However, the use of antibiotics is clearly associated with changes in gut microbiome composition and function, and perturbations have been identified as potential environmental risk factors for chronic inflammatory disorders of the gastrointestinal tract. In this Review, we examine the association between the use of antibiotics and the onset and development of both type 1 and type 2 diabetes, inflammatory bowel disease, including ulcerative colitis and Crohn's disease, as well as coeliac disease and eosinophilic oesophagitis. We discuss the key findings of epidemiological studies, provide mechanistic insights into the pathways by which the gut microbiota might contribute to these diseases, and assess clinical trials investigating the effects of antibiotics. Such studies indicate that antibiotic exposures, varying in type, timing and dosage, could explain differences in disease risk. There seems to be a critical window in early life in which perturbation of the microbiome has a substantial effect on disease development. Identifying the antibiotic-perturbed gut microbiota as a factor that contributes to the pathophysiology of these inflammatory disorders might stimulate new approaches to prevention, diagnosis and treatment.


Asunto(s)
Enfermedad de Crohn , Diabetes Mellitus Tipo 2 , Enfermedades Inflamatorias del Intestino , Humanos , Antibacterianos/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/etiología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico
16.
J Crohns Colitis ; 17(8): 1364-1368, 2023 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-36988432

RESUMEN

BACKGROUND AND AIMS: Faecal microbiota transplant [FMT] is effective in treating recurrent Clostridioides difficile infection [CDI] and restores gut microbiota composition. This is unlikely to account for its entire mechanism of efficacy, as studies have shown that factors such as bile acids influence the risk of infection by affecting Clostridioides difficile germination. We therefore aimed to investigate longitudinal changes in the gut bile acid composition after FMT performed for recurrent CDI, in children with and without inflammatory bowel disease [IBD]. METHODS: Eight children received FMT; five had underlying IBD. Primary and secondary faecal bile acids were measured by liquid chromatography-mass spectrometry in recipients [pre-FMT and longitudinally post-FMT for up to 6 months] and donors. RESULTS: Pre-FMT, recipients had higher primary and lower secondary bile acid proportions compared with donors. Post-FMT, there was a gradual increase of secondary and decrease of primary bile acids. Whereas gut bacterial diversity had been shown to be restored in all children shortly after FMT, normalisation of bile acids to donor levels occurred only by 6 months. In children with IBD, although microbiota diversity returned to pre-FMT levels within 6 months, secondary bile acids remained at donor levels. CONCLUSIONS: The differences in bile acid profiles compared with gut bacterial diversity post-FMT suggests that interactions between the two may be more complex than previously appreciated and may contribute to FMT efficacy in different ways. This initial finding demonstrates the need to further investigate gut metabolites in larger cohorts, with longitudinal sampling to understand the mechanisms of FMT effectiveness.


Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Enfermedades Inflamatorias del Intestino , Humanos , Niño , Trasplante de Microbiota Fecal/métodos , Ácidos y Sales Biliares , Recurrencia , Infecciones por Clostridium/terapia , Infecciones por Clostridium/microbiología , Enfermedades Inflamatorias del Intestino/complicaciones , Bacterias , Resultado del Tratamiento
18.
Aliment Pharmacol Ther ; 55(10): 1244-1264, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35355306

RESUMEN

INTRODUCTION: There are concerns regarding the effectiveness and safety of SARS-CoV-2 vaccine in inflammatory Bowel Disease (IBD) patients. This systematic review and meta-analysis comprehensively summarises the available literature regarding the safety and effectiveness of SARS-CoV-2 vaccine in IBD. METHODS: Three independent reviewers performed a comprehensive review of all original articles describing the response of SARS-CoV-2 vaccines in patients with IBD. Primary outcomes were (1) pooled seroconversion rate SARS-CoV-2 vaccination in IBD patients (2) comparison of breakthrough COVID-19 infection rate SARS-CoV-2 vaccination in IBD patients with control cohort and (3) pooled adverse event rate of SARS-CoV-2 vaccine. All outcomes were evaluated for one and two doses of SARS-CoV-2 vaccine. Meta-regression was performed. Probability of publication bias was assessed using funnel plots and with Egger's test. RESULTS: Twenty-one studies yielded a pooled seroconversion rate of 73.7% and 96.8% in IBD patients after one and two doses of SARS-CoV-2 vaccine respectively. Sub-group analysis revealed non-statistically significant differences between different immunosuppressive regimens for seroconversion. Meta-regression revealed that the vaccine type and study location independently influenced seroconversion rates. There was no statistically significant difference in breakthrough infection in IBD patients as compared to control after vaccination. CONCLUSION: In summary, the systematic review and meta-analysis suggest that SARS-CoV-2 vaccine is safe and effective in IBD patients.


Asunto(s)
COVID-19 , Enfermedades Inflamatorias del Intestino , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , SARS-CoV-2 , Vacunación
19.
Gastro Hep Adv ; 1(6): 909-915, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35874930

RESUMEN

Background and Aims: Gastrointestinal (GI) symptoms occur among patients diagnosed with coronavirus disease 2019 (COVID-19), and there is clear evidence that SARS-CoV-2, the causative pathogen, infects the GI tract. In this large, multicenter cohort study, we evaluated variations in gastrointestinal and hepatic manifestations of COVID-19 throughout the United States (US). Methods: Patients hospitalized with a positive COVID-19 test prior to October 2020 were identified at 7 US academic centers. Demographics, presenting symptoms, laboratory data, and hospitalization outcomes were abstracted. Descriptive and regression analyses were used to evaluate GI manifestations and their potential predictors. Results: Among 2031 hospitalized patients with COVID-19, GI symptoms were present in 18.9%; diarrhea was the most common (15.2%), followed by nausea and/or vomiting (12.6%) and abdominal pain (6.0%). GI symptoms were less common in the Western cohort (16.0%) than the Northeastern (25.6%) and Midwestern (26.7%) cohorts. Compared to nonintensive care unit (ICU) patients, ICU patients had a higher prevalence of abnormal aspartate aminotransferase (58.1% vs 37.3%; P < .01), alanine aminotransferase (37.5% vs 29.3%; P = .01), and total bilirubin (12.7% vs 9.0%; P < .01). ICU patients also had a higher mortality rate (22.7% vs 4.7%; P < .01). Chronic liver disease was associated with the development of GI symptoms. Abnormal aspartate aminotransferase or alanine aminotransferase was associated with an increased risk of ICU admission. Conclusion: We present the largest multicenter cohort of patients with COVID-19 across the United States. GI manifestations were common among patients hospitalized with COVID-19, although there was significant variability in prevalence and predictors across the United States.

20.
J Clin Gastroenterol ; 44(1): 9-11, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19713865

RESUMEN

GOALS: The purpose of this study is to determine the weight given to each of 3 pain dimensions by physicians who assess patients' pain experiences. BACKGROUND: Pain is a subjective experience that has profound impact on the quality of life. The 101-Multidimensional Affect and Pain Survey (101-MAPS) is currently the only available instrument that takes into account all 3 validated dimensions of pain by classifying 101 items into "superclusters" of sensory pain, suffering, and well-being. STUDY: Fourteen gastroenterologists, 11 internists, and 11 medicine residents from 2 teaching hospitals rated the items on the 101-MAPS based on their perception of the items' relevance to pain in gastrointestinal diseases, on a scale of 0 (least relevant) to 5 (most relevant). RESULTS: Of the 101 items in the MAPS rated by gastroenterologists, 25 items received a median rating of 4 or above. Of these, 23 were selected from the 57 items in the sensory pain supercluster (40%) and only 1 item each from the 26 in the suffering (3.8%), and the 18 in the well-being (5.5%) dimensions. These proportions were significantly lower for the suffering (P<0.01) and well-being (P<0.05) superclusters than for the sensory pain dimension. CONCLUSIONS: These findings suggest a bias among physicians toward sensory and against affective qualities when eliciting patients' pain experiences. The results also suggest that this bias is found as early as residency training and persists among specialists.


Asunto(s)
Actitud del Personal de Salud , Dimensión del Dolor/métodos , Dolor/diagnóstico , Médicos/psicología , Adulto , Anciano , Análisis por Conglomerados , Femenino , Enfermedades Gastrointestinales/fisiopatología , Encuestas Epidemiológicas , Hospitales de Enseñanza , Humanos , Internado y Residencia , Masculino , Persona de Mediana Edad , Dolor/etiología , Dolor/fisiopatología , Percepción , Calidad de Vida , Encuestas y Cuestionarios
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