Fecal Metabolome and Bacterial Composition in Severe Obesity:Impact of Diet and Bariatric Surgery

The aim of this study was to monitor the impact of a preoperative low-calorie diet and bariatric surgery on the bacterial gut microbiota composition and functionality in severe obesity and to compare sleeve gastrectomy (SG) versus Roux-en-Y gastric bypass (RYGB). The study also aimed to incorporate big data analysis for the omics results and machine learning by a Lasso-based analysis to detect the potential markers for excess weight loss. Forty patients who underwent bariatric surgery were recruited (14 underwent SG, and 26 underwent RYGB). Each participant contributed 4 fecal samples (baseline, post-diet, 1 month after surgery and 3 months after surgery). The bacterial composition was determined by 16S rDNA massive sequencing using MiSeq (Illumina). Metabolic signatures associated to fecal concentrations of short-chain fatty acids, amino acids, biogenic amines, gamma-aminobutyric acid and ammonium were determined by gas and liquid chromatography. Orange 3 software was employed to correlate the variables, and a Lasso analysis was employed to predict the weight loss at the baseline samples. A correlation between Bacillota (formerly Firmicutes) abundance and excess weight was observed only for the highest body mass indexes. The low-calorie diet had little impact on composition and targeted metabolic activity. RYGB had a deeper impact on bacterial composition and putrefactive metabolism than SG, although the excess weight loss was comparable in the two groups. Significantly higher ammonium concentrations were detected in the feces of the RYGB group. We detected individual signatures of composition and functionality, rather than a gut microbiota characteristic of severe obesity, with opposing tendencies for almost all measured variables in the two surgical approaches. The gut microbiota of the baseline samples was not useful for predicting excess weight loss after the bariatric process

Impacto de la cirugía bariátrica en la microbiota intestinal y el metaboloma fecal

Resumen del trabajo presentado a la 14ª Reunión de la Red Española de Bacterias Lácticas (RedBAl), celebrada de forma telemática del 8 al 10 de Septiembre de 2021.Introducción: El tratamiento de la obesidad severa mediante cirugía bariátrica presenta la mejor relación efectividad/coste, siendo el sleeve gástrico (SG) y el bypass gástrico (BPG) las técnicas laparoscópicas más utilizadas. El BPG está recomendado en pacientes con mayor exceso de peso (IMC>50). Aunque se han descrito alteraciones en la microbiota intestinal (MI) en relación con la obesidad, existen pocos estudios en obesidad severa en los que se haya caracterizado este ecosistema y el metaboloma fecal. Objetivos: Evaluar el impacto de la dieta pre-operatoria y la técnica de cirugía bariátrica sobre la MI y el metaboloma fecal en obesidad severa. Sujetos y métodos: Se incluyeron 40 pacientes de cirugía bariátrica (14 SG y 26 BPG), se recogió información clínica de interés, así como muestras de heces a cuatro tiempos: 1)-basal, 2)-tras dieta preoperatoria, 3)-al mes y 4)- a los tres meses de la cirugía. Se determinó la composición de la MI mediante secuenciación del gen ARNr 16S y la concentración fecal de varios metabolitos (ácidos grasos de cadena corta-AGCC, aminoácidos y aminas biógenas-AB) mediante cromatografía de gases y líquida. Resultados: Se han detectado diferencias significativas en la composición de la MI de la muestra basal de los pacientes de BPG y de SG y cambios estadísticamente significativos en la composición de la MI y en el metaboloma fecal entre las cuatro muestras, existiendo un mayor impacto en el BPG. En el caso del patrón fecal de AGCC, ambas cirugías disminuyeron la concentración de los AGCC mayoritarios, aunque no hubo diferencias significativas entre ambas. La concentración fecal de aminoácidos transcurridos tres meses desde la operación fue en general inferior en el grupo de pacientes sometidos a BPG, mientras que la concentración de AB fue superior en comparación con los individuos operados mediante SG. Conclusiones: Los pacientes con obesidad severa e IMC>50 tienen una MI diferente, con mayor abundancia de Firmicutes. La cirugía bariátrica y la dieta preoperatoria asociada modifican la composición de la MI y el perfil de metabolitos fecales, siendo estos cambios más profundos cuando se utiliza la técnica de BPG, probablemente por la alteración anatómica del tránsito intestinal

A body weight loss- and health-promoting gut microbiota is established after bariatric surgery in individuals with severe obesity

Obesity has reached an epidemic level worldwide, and bariatric surgery (BS) has been proven to be the most efficient therapy to reduce severe obesity-related comorbidities. Given that the gut microbiota plays a causal role in obesity development and that surgery may alter the gut environment, investigating the impact of BS on the microbiota in the context of severe obesity is important. Although, alterations at the level of total gut bacteria, total gene content and total metabolite content have started to be disentangled, a clear deficit exists regarding the analysis of the active fraction of the microbiota, which is the fraction that is most reactive to the BS. Here, active gut microbiota and associated metabolic functions were evaluated using shotgun proteomics and metabolomics in 40 severely obese volunteers. Samples from each volunteer were obtained under basal conditions, after a short high protein and calorie-restricted diet, and 1 and 3 months after BS, including laparoscopic surgery through Roux-en-Y Gastric Bypass or Sleeve Gastrectomy. The results revealed for the first time the most active microbes and metabolic flux distribution pre- and post-surgery and deciphered main differences in the way sugars and short-fatty acids are metabolized, demonstrating that less energy-generating and anaerobic metabolism and detoxification mechanisms are promoted post-surgery. A comparison with non-obese proteome data further signified different ways to metabolize sugars and produce short chain fatty acids and deficiencies in proteins involved in iron transport and metabolism in severely obese individuals compared to lean individuals.This work was funded by grants SAF2015-65878-R, BIO2017-85522-R, PID2019-105969GB-I00 and RTI2018-095166-B-I00 from the Ministry of Science, Innovation and Universities, by the Ministry of Science and Innovation, by the Instituto de Salud Carlos III (projects PIE14/00045 and AC17/00022), Fundación Agencia Española contra el Cáncer and Instituto de Salud Carlos III(projects ERA NET TRANSCAN-2 AC17/00022 and AECC 2017-1485), Generalitat Valenciana (project Prometeo/2018/A/133) and co-financed by the European Regional Development Fund (ERDF). The proteomic analysis was performed in the Proteomics Facility of The Spanish National Center for Biotechnology (CNB-CSIC) that belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019.Peer reviewe

Correction : Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885

The authors wish to make the following corrections to this paper [...]

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain : Large-Scale Epidemiological Study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Impacto de la cirugía bariátrica en la composición y la actividad metabólica de la microbiota intestinal

Resumen trabajo presentado en el XII Workshop Sociedad Española de Microbiota, Probióticos y Prebióticos (SEMiPyP) y I Congreso Sociedad Iberoamericana de Microbiota, Probióticos y Prebióticos (SIAMPYP), celebrado de forma virtual del 15 al 18 de septiembre de 2021Introducción/objetivos. El tratamiento de la obesidad severa mediante cirugía bariátrica presenta la mejor relación efectividad/coste, siendo el sleeve gástrico (SG) y el bypass gástrico (BPG) las técnicas laparoscópicas más utilizadas. El BPG está recomendado con IMC > 50. Aunque se han descrito alteraciones en la microbiota intestinal (MI) en relación con la obesidad, existen pocos estudios en obesidad severa en los que se haya caracterizado este ecosistema. El objetivo del trabajo fue evaluar el impacto de la dieta pre-operatoria y el tipo de cirugía bariátrica sobre la composición y la actividad metabólica de la MI en obesidad severa. Metodología. Se incluyeron 40 pacientes de cirugía bariátrica (14 SG y 26 BPG), recogiendo la información clínica de interés. Cada paciente contribuyó con 4 muestras de heces: 1) basal, 2) tras dieta preoperatoria, 3) al mes y 4) a los tres meses de la cirugía. Se determinó la composición de la MI mediante secuenciación del gen ARNr 16S y la producción de ácidos grasos de cadena corta (AGCC) mediante cromatografía de gases. Resultados. Se han detectado diferencias significativas en la composición de la MI de la muestra basal de los pacientes de BPG y de SG y cambios estadísticamente significativos en la composición y actividad metabólica entre las cuatro muestras, existiendo un mayor impacto en el BPG. En el caso del patrón de AGCC, ambas cirugías disminuyeron la concentración de los AGCC mayoritarios, existiendo tendencias opuestas en la evolución de las 4 muestras, pero sin diferencias significativas entre cirugías. Conclusiones. Los obesos severos con elevado exceso de peso (IMC> 50) tienen una MI diferente, con mayor abundancia de Firmicutes. La cirugía bariátrica y la dieta preoperatoria asociada modifican la composición y la funcionalidad de la MI; siendo estos cambios más profundos cuando se utiliza la técnica de BPG, probablemente por la alteración anatómica del tránsito intestinal