RESUMEN
Inflammatory bowel disease (IBD) is an emerging global disease characterised by chronic inflammation of the gastrointestinal tract. However, IBD is also manifested by several extraintestinal symptoms which, along with the intestinal symptoms, impact on the mental and emotional well-being of patients. Despite therapeutic advancements, only one-third of the diagnosed patients receiving approved medical treatments achieve short-term to medium-term remission. Consequently, patients who do not get successfully treated might resort to using complementary and alternative approaches to manage their symptoms, with or without consulting their treating clinician. Despite their possible potential, such approaches have various risks stemming from unknown adverse reactions and possible interference with medically approved therapies. In this study, we present the results of a well-performed literature review where we included randomised clinical trials which have assessed the efficacy of complementary approaches and dietary therapy on at least one of the following four outcomes: clinical remission, endoscopic remission, modulation of molecular biomarkers or quality of life metrics. By pointing out intraoutcome and interoutcome concordance, we identified possible candidates for clinical adoption and further study in larger randomised clinical trials covering the broad spectrum of IBD heterogeneity. We finally proposed a patient-centric clinical care model and a series of recommendations for stakeholders, with special attention to complementary approaches and dietary strategies, aimed at achieving holistic remission.
Asunto(s)
Enfermedades Inflamatorias del Intestino , Calidad de Vida , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Dieta , Atención a la Salud , Atención Dirigida al Paciente , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
While differential antibody responses SARS-CoV-2 in patients with inflammatory bowel disease (IBD) receiving infliximab and vedolizumab are well-characterized, the immune pathways underlying these differences remain unknown. Prior to COVID-19 vaccine development, we screened 235 patients with IBD receiving biological therapy for antibodies to SARS-CoV-2 and measured serum cytokines. In seropositive patients, we prospectively collected clinical data. We found a cytokine signature in patients receiving vedolizumab who are seropositive compared with seronegative for SARS-CoV-2 antibodies that may be linked to repeated SARS-CoV-2 infections. However, there were no differences between seropositive and seronegative patients receiving infliximab. In this single-center cohort of patients with IBD with anti-SARS-CoV-2 antibodies at the onset of the COVID-19 pandemic, and therefore without influence of vaccination, there is a cytokine signature in patients receiving vedolizumab but not infliximab. These findings lay the groundwork for further studies on immune consequences of viral infection in patients with IBD, which is postulated to evolve from aberrant host-microbe responses.
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COVID-19 , Enfermedades Inflamatorias del Intestino , Humanos , SARS-CoV-2 , Vacunas contra la COVID-19 , Infliximab/uso terapéutico , Pandemias , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Antivirales , Citocinas , Enfermedades Inflamatorias del Intestino/tratamiento farmacológicoRESUMEN
This work aims to investigate how smoking exerts effect on the development of inflammatory bowel disease (IBD). A prospective cohort study and a Mendelian randomization study are first conducted to evaluate the association between smoking behaviors, smoking-related DNA methylation and the risks of Crohn's disease (CD) and ulcerative colitis (UC). We then perform both genome-wide methylation analysis and co-localization analysis to validate the observed associations. Compared to never smoking, current and previous smoking habits are associated with increased CD (P = 7.09 × 10-10) and UC (P < 2 × 10-16) risk, respectively. DNA methylation alteration at cg17742416 [DNMT3A] is linked to both CD (P = 7.30 × 10-8) and UC (P = 1.04 × 10-4) risk, while cg03599224 [LTA/TNF] is associated with CD risk (P = 1.91 × 10-6), and cg14647125 [AHRR] and cg23916896 [AHRR] are linked to UC risk (P = 0.001 and 0.002, respectively). Our study identifies biological mechanisms and pathways involved in the effects of smoking on the pathogenesis of IBD.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Fumar/efectos adversos , Fumar/genética , Metilación de ADN , Estudios Prospectivos , Enfermedades Inflamatorias del Intestino/genética , Enfermedad de Crohn/genética , Colitis Ulcerosa/genética , Proteínas Represoras/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genéticaRESUMEN
BACKGROUND & AIMS: Ultra-processed food (UPF) intake has increased sharply over the last few decades and has been consistently asserted to be implicated in the development of non-communicable diseases. We aimed to evaluate and update the existing observational evidence for associations between ultra-processed food (UPF) consumption and human health. METHODS: We searched Medline and Embase from inception to March 2023 to identify and update meta-analyses of observational studies examining the associations between UPF consumption, as defined by the NOVA classification, and a wide spectrum of health outcomes. For each health outcome, we estimated the summary effect size, 95% confidence interval (CI), between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. These metrics were used to evaluate evidence credibility of the identified associations. RESULTS: This umbrella review identified 39 meta-analyses on the associations between UPF consumption and health outcomes. We updated all meta-analyses by including 122 individual articles on 49 unique health outcomes. The majority of the included studies divided UPF consumption into quartiles, with the lowest quartile being the reference group. We identified 25 health outcomes associated with UPF consumption. For observational studies, 2 health outcomes, including renal function decline (OR: 1.25; 95% CI: 1.18, 1.33) and wheezing in children and adolescents (OR: 1.42; 95% CI: 1.34, 1.49), showed convincing evidence (Class I); and five outcomes were reported with highly suggestive evidence (Class II), including diabetes mellitus, overweight, obesity, depression, and common mental disorders. CONCLUSIONS: High UPF consumption is associated with an increased risk of a variety of chronic diseases and mental health disorders. At present, not a single study reported an association between UPF intake and a beneficial health outcome. These findings suggest that dietary patterns with low consumption of UPFs may render broad public health benefits.
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Comida Rápida , Estudios Observacionales como Asunto , Humanos , Comida Rápida/estadística & datos numéricos , Comida Rápida/efectos adversos , Manipulación de Alimentos , Dieta/estadística & datos numéricos , Metaanálisis como Asunto , Femenino , Alimentos ProcesadosRESUMEN
Inflammatory bowel diseases (IBD) are chronic and incurable conditions of the gastro-intestinal tract with an increasing incidence and prevalence worldwide. Common symptoms are abdominal pain, diarrhea, and weight loss. Despite recent advances in medical management, many patients fail to achieve clinical remission and healing of the mucosa of the bowel. The cause is thought to involve an inappropriate reaction of the immune system, the microbiome and the environment in genetically susceptible individuals, leading to chronic bowel inflammation. Evidence is emerging that diet is a key environmental factor that might influence disease onset and course, and therefore may become a therapeutic strategy to mitigate inflammation and symptoms. Since IBD is a heterogeneous disease on a clinical and a molecular level, personalizing dietary advice could be the crucial factor to achieve long-lasting changes in dietary behaviors that could not only improve nutritional status but also tackle gut inflammation and abdominal symptoms on an individual level. In this review, we first discuss different aspects of personalized nutrition, namely the level, focus, and scope of personalized dietary regimens. Then, we provide a framework for the different goals of nutritional therapy in IBD and current evidence for personalized dietary approaches. Lastly, we discuss the need for adequate trial designs, access to the right data types and the bioinformatic tools that are necessary to develop algorithms that will allow us to move from general "healthy eating" advice to truly personalized nutritional plans for the individual IBD patient.
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BACKGROUND AND AIMS: Ultra-processed food [UPF] consumption has been linked to globally increasing incidence and prevalence of chronic diseases, including inflammatory bowel diseases [IBD]. We aimed to investigate the association between UPF consumption and IBD incidence, prevalence, and IBD-relevant outcomes. METHODS: We performed a cross-sectional and prospective cohort study in 187 854 individuals included in the national UK Biobank, using 24-h dietary recall questionnaires. Multivariable logistic regression and Cox proportional hazard regression were used to examine the association between UPFs and the prevalence and incidence risk of IBD, respectively. RESULTS: A total of 185 849 participants with a mean age of 56.2 were included, with a mean follow-up of 9.84 years. During follow-up, 841 developed IBD (251 Crohn's disease [CD], and 590 ulcerative colitis [UC]). UPF intake in IBD patients was significantly higher: CD: odds ratio [OR] 1.94 (95% confidence interval [CI]: 1.52, 2.49, pâ <0.001); UC: OR 1.39 [95% CI: 1.17, 1.65, pâ <0.001]. Compared with low consumption, higher UPF consumption was significantly associated with incident CD: hazard ration [HR] 2.00 [95% CI: 1.32, 3.03, pâ =â 0.001], but not UC. We also found a significant association between UPF intake and need of IBD-related surgery: HR 4.06 [95% CI: 1.52, 10.86, pâ =â 0.005]. CONCLUSION: Higher intake of UPFs was associated with higher incidence of CD, but not UC. In individuals with a pre-existing diagnosis of IBD, consumption of UPFs was significantly higher compared with controls, and was associated with an increased need for IBD-related surgery. Further studies are needed to address the impact of UPF intake on disease pathogenesis and outcomes.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Persona de Mediana Edad , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/etiología , Enfermedad de Crohn/diagnóstico , Estudios Prospectivos , Alimentos Procesados , Bancos de Muestras Biológicas , Estudios Transversales , Factores de Riesgo , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/etiología , Colitis Ulcerosa/diagnóstico , Enfermedades Inflamatorias del Intestino/complicaciones , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Beyond systematic reviews and meta-analyses, there have been no direct studies of serological response to COVID-19 in patients with inflammatory bowel disease (IBD) across continents. In particular, there has been limited data from Asia, with no data reported from India. The ICARUS-IBD (International study of COVID-19 Antibody Response Under Sustained immunosuppression in IBD) consortium assessed serological response to SARS-CoV-2 in patients with IBD in North America, Europe, and Asia. METHODS: The ICARUS-IBD study is a multicenter observational cohort study spanning sites in 7 countries. We report seroprevalence data from 2303 patients with IBD before COVID-19 vaccination between May 2020 and November 2021. SARS-CoV-2 anti-spike and anti-nucleocapsid antibodies were analyzed. RESULTS: The highest and lowest SARS-CoV-2 anti-spike seropositivity rates were found in Asia (81.2% in Chandigarh and 57.9% in Delhi, India; and 0% in Hong Kong). By multivariable analysis, country (India: odds ratio [OR], 18.01; 95% confidence interval [CI], 12.03-26.95; P < .0001; United Kingdom: OR, 2.43; 95% CI, 1.58-3.72; P < .0001; United States: OR, 2.21; 95% CI, 1.27-3.85; P = .005), male sex (OR, 1.46; 95% CI, 1.07-1.99; P = .016), and diabetes (OR, 2.37; 95% CI, 1.04-5.46; P = .039) conferred higher seropositivity rates. Biological therapies associated with lower seroprevalence (OR, 0.22; 95% CI, 0.15-0.33; P < .0001). Multiple linear regression showed associations between anti-spike and anti-nucleocapsid titers with medications (P < .0001) but not with country (P = .3841). CONCLUSIONS: While the effects of medications on anti-SARS-CoV-2 antibody titers in patients with IBD were consistent across sites, geographical location conferred the highest risk of susceptibility to serologically detectable SARS-CoV-2 infection. Over half of IBD patients in India were seropositive prior to vaccination. These insights can help to inform shielding advice, therapeutic choices, and vaccine strategies in IBD patients for COVID-19 and future viral challenges.
In this multinational study of SARS-CoV-2 seroprevalence prior to vaccination, including the first data from India, where over half of patients seroconverted, geographical location conferred the highest risk of susceptibility to serologically detectable infection.
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COVID-19 , Enfermedades Inflamatorias del Intestino , Humanos , Masculino , SARS-CoV-2 , Vacunas contra la COVID-19 , Estudios Seroepidemiológicos , Geografía , Anticuerpos AntiviralesRESUMEN
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract, and the exact pathogenesis is still unclear. It is believed that IBD develops in response to a complex interaction between the microbiota, environmental factors, and the immune system, in genetically predisposed individuals. Identifying these environmental factors will offer more insight in the development of the disease, and reveal new therapeutic targets for IBD patients. One of the environmental factors that has gained more interest over the last years is our diet. The prevalence of IBD has increased significantly and this increase is thought to be associated with a 'Western diet', characterized by high intake of fats, added sugar, meat, and ultra-processed foods (UPFs). The UPFs now account for almost 50% of the energy intake in Westernized countries and are therefore an important characteristic of this Western diet. UPFs are characterized by higher amounts of salt, fat, sugar and the presence of different food additives. Epidemiological studies have found associations between UPF intake and a range of non-communicable diseases, including inflammatory bowel disease (IBD). Preclinical and clinical evidence suggest that non-nutritive ingredients and additives, present in UPFs, can negatively affect different components of the intestinal barrier, such as the microbiota, the mucus layer, the epithelium, and the immune cells in the lamina propria. Disruption of this barrier can cause the immune system to encounter an increased bacterial exposure, leading to an aberrant immune response. In this article, the available evidence on the possible role of UPFs and their components in the increasing incidence and prevalence of IBD is reviewed. These findings can be translated to the clinic and may be helpful to consider when giving dietary advice to IBD patients. A better understanding of the role of UPFs may lead to less restrictive diets for patients with IBD, hence increasing the dietary compliance and efficacy of exclusion diets.
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Inflammatory bowel disease [IBD] has a multifactorial origin and originates from a complex interplay of environmental factors with the innate immune system at the intestinal epithelial interface in a genetically susceptible individual. All these factors make its aetiology intricate and largely unknown. Multi-omic datasets obtained from IBD patients are required to gain further insights into IBD biology. We here review the landscape of multi-omic data availability in IBD and identify barriers and gaps for future research. We also outline the various technical and non-technical factors that influence the utility and interpretability of multi-omic datasets and thereby the study design of any research project generating such datasets. Coordinated generation of multi-omic datasets and their systemic integration with clinical phenotypes and environmental exposures will not only enhance understanding of the fundamental mechanisms of IBD but also improve therapeutic strategies. Finally, we provide recommendations to enable and facilitate generation of multi-omic datasets.
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Enfermedades Inflamatorias del Intestino , Exposición a Riesgos Ambientales , Predisposición Genética a la Enfermedad , Humanos , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/terapia , FenotipoRESUMEN
The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to an ICU with fatal and nonfatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an "original antigenic sin" type response.
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COVID-19 , Glicoproteína de la Espiga del Coronavirus , Anticuerpos Antivirales , Formación de Anticuerpos , Epítopos , Humanos , SARS-CoV-2RESUMEN
The food we eat is thought to play a role in both the increasing incidence as well as the course of Crohn's disease. What to eat and what to avoid is an increasingly important question for both patients and physicians. Restrictive diets are widely adopted by patients and carry the risk of inducing or worsening malnutrition, without any guarantees on anti-inflammatory potential. Nevertheless, exploration of novel therapies to improve long-term management of the disease is desperately needed and the widespread use of exclusive enteral nutrition in the induction of paediatric Crohn's disease makes us wonder if a similar approach would be beneficial in adult patients. This narrative review discusses the current clinical evidence on whole food diets in achieving symptomatic and inflammatory control in Crohn's disease and identifies knowledge gaps with areas for future research.
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Enfermedad de Crohn/terapia , Dietoterapia/métodos , Adulto , Niño , Nutrición Enteral/métodos , Femenino , Humanos , Masculino , Inducción de Remisión/métodosRESUMEN
Since the beginning of the pandemic, patients with inflammatory bowel diseases [IBD] have been considered at high risk for infection and complications of COVID-19. IBD patients and patients taking immunosuppressive therapy were excluded from clinical phase III vaccine trials, complicating the assessment of effectiveness of these new vaccines. From past experience we know that adapted vaccination strategies may be appropriate in some IBD patients to optimise immunogenicity. We review current evidence on SARS-CoV-2 vaccination relevant to IBD patients, including immune responses from humoral to cellular, emerging data on new variants, and off-label vaccination schemes. We also identify clinical and scientific knowledge gaps that can be translated into both large-scale population-based studies and targeted vaccine studies to describe the precise immune responses induced by SARS-CoV-2 vaccines in IBD patients. We strongly endorse the recommendation of vaccinating IBD patients to ensure maximal protection from COVID-19 both for the individual and the community.
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Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , Inmunosupresores/inmunología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Vacunación , Humanos , Inmunidad Celular , Inmunidad Humoral , Inmunosupresores/uso terapéutico , SARS-CoV-2 , Vacunación/métodosRESUMEN
The antigenic drift theory states that influenza evolves via the gradual accumulation of mutations, decreasing a host's immune protection against previous strains. Influenza vaccines are designed accordingly, under the premise of antigenic drift. However, a paradox exists at the centre of influenza research. If influenza evolved primarily through mutation in multiple epitopes, multiple influenza strains should co-circulate. Such a multitude of strains would render influenza vaccines quickly inefficacious. Instead, a single or limited number of strains dominate circulation each influenza season. Unless additional constraints are placed on the evolution of influenza, antigenic drift does not adequately explain these observations. Here, we explore the constraints placed on antigenic drift and a competing theory of influenza evolution - antigenic thrift. In contrast to antigenic drift, antigenic thrift states that immune selection targets epitopes of limited variability, which constrain the variability of the virus. We explain the implications of antigenic drift and antigenic thrift and explore their current and potential uses in the context of influenza vaccine design.
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Empirical dietary inflammatory pattern and the dietary inflammatory index are dietary inflammation indices, both previously associated with risk of inflammatory bowel disease. We show in the UK Biobank a null association between these indices and incident inflammatory bowel disease; we challenge the current ways in which these dietary indices are derived and interpreted. The need to account for the effects of food processing as well as the raw ingredients is emphasized as a confounding variable.