Virulence Factors of the Gut Microbiome Are Associated with BMI and Metabolic Blood Parameters in Children with Obesity.

The development of metabolic diseases is linked to the gut microbiota. A cross-sectional study involving 45 children (6 to 12 years old) was conducted to investigate the relationship between gut microbiota and childhood obesity. Anthropometric and metabolic measurements, food-frequency questionnaires (FFQs), and feces samples were obtained. Using the body mass index (BMI) z-score, we categorized each participant as normal weight (NW), or overweight and obese (OWOB). We determined 2 dietary profiles: one with complex carbohydrates and proteins (pattern 1), and the other with saturated fat and simple carbohydrates (pattern 2). The microbial taxonomic diversity and metabolic capacity were determined using shotgun metagenomics. We found differences between both BMI groups diversity. Taxa contributing to this difference, included Eubacterium sp., Faecalibacterium prausnitzii, Dialister, Monoglobus pectinilyticus, Bifidobacterium pseudocatenulatum, Intestinibacter bartlettii, Bacteroides intestinalis, Bacteroides uniformis, and Methanobrevibacter smithii. Metabolic capacity differences found between NW and OWOB, included the amino acid biosynthesis pathway, the cofactor, carrier, and vitamin biosynthesis pathway, the nucleoside and nucleotide biosynthesis and degradation pathways, the carbohydrate-sugar degradation pathway, and the amine and polyamine biosynthesis pathway. We found significant associations between taxa such as Ruminococcus, Mitsuokella multacida, Klebsiella variicola, and Citrobacter spp., metabolic pathways with the anthropometric, metabolic, and dietary data. We also found the microbiome's lipooligosaccharide (LOS) category as differentially abundant between BMI groups. Metabolic variations emerge during childhood as a result of complex nutritional and microbial interactions, which should be explained in order to prevent metabolic illnesses in adolescence and maturity. IMPORTANCE The alteration of gut microbiome composition has been commonly observed in diseases involving inflammation, such as obesity and metabolic impairment. Inflammatory host response in the gut can be a consequence of dietary driven dysbiosis. This response is conducive to blooms of particular bacterial species, adequate to survive in an inflammatory environment by means of genetical capability of utilizing alternative nutrients. Understanding the genomic and metabolic contribution of microbiota to inflammation, including virulence factor prevalence and functional potential, will contribute to identifying modifiable early life exposures and preventive strategies associated with obesity risk in childhood.

The Mexican consensus on probiotics in gastroenterology. / Consenso mexicano sobre probióticos en gastroenterología.

INTRODUCTION: Probiotics are frequently prescribed in clinical practice. Their efficacy in treating gastrointestinal disorders is supported by a significant number of clinical trials. However, the correct prescription of these agents is hampered due to a lack of knowledge of the scientific evidence and to the different presentations and microbial compositions of the probiotics that are currently available. AIM: To provide the clinician with a consensus review of probiotics and recommendations for their use in gastroenterology. MATERIALS AND METHODS: Controlled clinical trials, meta-analyses, and systematic reviews published up to 2015 were selected, using the MESH terms: probiotics, gastrointestinal diseases, humans, adults, AND children. The Delphi method was employed. Eighteen gastroenterologists treating adult patients and 14 pediatric gastroenterologists formulated statements that were voted on until agreement>70% was reached. The level of evidence based on the GRADE system was evaluated for each statement. RESULTS AND CONCLUSIONS: Eleven statements on the general concepts of probiotics and 27 statements on the use of probiotics in gastrointestinal diseases in both adults and children were formulated. The consensus group recommends the use of probiotics under the following clinical conditions: the prevention of diarrhea associated with antibiotics, the treatment of acute infectious diarrhea, the prevention of Clostridium difficile infection and necrotizing enterocolitis, the reduction of adverse events from Helicobacter pylori eradication therapy, relief from irritable bowel syndrome symptoms, the treatment of functional constipation in the adult, and the induction and maintenance of remission in patients with ulcerative colitis and pouchitis, and the treatment of covert and overt hepatic encephalopathy.

Risk allelic load in Th2 and Th3 cytokines genes as biomarker of susceptibility to HPV-16 positive cervical cancer: a case control study.

BACKGROUND: Alterations in the host cellular immune response allow persistent infections with High-Risk Human Papillomavirus (HR-HPV) and development of premalignant cervical lesions and cervical cancer (CC). Variations of immunosuppressive cytokine levels in cervix are associated with the natural history of CC. To assess the potential role of genetic host immunity and cytokines serum levels in the risk of developing CC, we conducted a case-control study paired by age. METHODS: Peripheral blood samples from patients with CC (n = 200) and hospital controls (n = 200), were used to evaluate nine biallelic SNPs of six cytokine genes of the adaptive immune system by allelic discrimination and cytokines serum levels by ELISA. RESULTS: After analyzing the SNP association by multivariate logistic regression adjusted by age, CC history and smoking history, three Th2 cytokines (IL-4, IL-6 and IL-10) and one Th3 (TGFB1) cytokine were significantly associated with CC. Individuals with at least one copy of the following risk alleles: T of SNP (-590C > T IL-4), C of SNP (-573G > C IL-6), A of SNP (-592C > A IL-10), T of SNP (-819C > T IL-10) and T of SNP (-509C > T TGFB1), had an adjusted odds ratio (OR) of 2.08 (95 % CI 1.475-2.934, p = 0.0001), an OR of 1.70 (95 % CI 1.208-2.404, p = 0.002), an OR of 1.87 (95 % CI 1.332-2.630, p = 0.0001), an OR of 1.67 (95 % CI 1.192-2.353, p = 0.003) and an OR of 1.91 (95 % CI 1.354-2.701, p = 0.0001), respectively, for CC. The burden of carrying two or more of these risk alleles was found to have an additive effect on the risk of CC (p trend = 0.0001). Finally, the serum levels of Th2 and Th3 cytokines were higher in CC cases than the controls; whereas IFNG levels, a Th1 cytokine, were higher in controls than CC cases. CONCLUSION: The significant associations of five SNPs with CC indicate that these polymorphisms are potential candidates for predicting the risk of development of CC, representing a risk allelic load for CC and can be used as a biomarker of susceptibility to this disease.

Cervical cancer-associated promoter polymorphism affects akna expression levels.

Cervical cancer (CC) is responsible for >260,000 deaths worldwide each year. Efforts are being focused on identifying genetic susceptibility factors, especially in genes related to the immune response. Akna has been proposed to be one of them, but data regarding its functional role in the disease is scarce. Supporting the notion of akna as a CC susceptibility gene, we found two polymorphisms associated with squamous intraepithelial lesion (SIL) and CC; moreover, we identified an association between high akna expression levels and CC and SIL, but its direction differs in each disease stage. To show the potential existence of a cis-acting polymorphism, we assessed akna allelic expression imbalance for the alleles of the -1372C>A polymorphism. We found that, regardless of the study group, the number of transcripts derived from the A allele was significantly higher than those from the C allele. Our results support the hypothesis that akna is a CC susceptibility genetic factor and suggest that akna transcriptional regulation has a role in the disease. We anticipate our study to be a starting point for in vitro evaluation of akna transcriptional regulation and for the identification of transcription factors and cis-elements regulating AKNA function that are involved in carcinogenesis.

IRS1, TCF7L2, ADRB1, PPARG, and HHEX polymorphisms associated with atherogenic risk in Mexican population.

Objective. We aimed to explore the association between polymorphisms of IRS1 (rs1801278), TCF7L2 (rs7903146 and rs12255372), ADRB1 (rs1801253), PPARG (rs1801282), and HHEX (rs5015480) genes with atherogenic risk (AI = Total cholesterol/HDL) in MetS, T2D, and healthy populations from the Mexican Social Security Institute. Methodology and Results. Four hundred thirty-five MetS, 517 T2D, and 547 healthy individuals were selected. The association between the SNPs and the atherogenic index was evaluated by multiple linear regression and multinomial logistic regression models. The ADRB1 gene showed a statistically significant association with high-risk atherogenic index, OR = 2.94 (IC 95% 1.64-5.24; P < 0.0001) for the Arg/Gly variant, under the dominant model an OR = 2.96 (IC 95% 1.67-5.25; P < 0.0001), and under the Log additive model an OR = 2.52 (IC 95% 1.54-4.15; P < 0.0001). Conclusions. The Arg389Gly polymorphism of the ADRB1 gene may be a worthy biological marker to predict the risk of developing cardiovascular diseases given a high-risk atherogenic index.

Candidate gene association study conditioning on individual ancestry in patients with type 2 diabetes and metabolic syndrome from Mexico City.

BACKGROUND: Type 2 diabetes (T2D) is influenced by diverse environmental and genetic risk factors. Metabolic syndrome (MS) increases the risk of cardiovascular disease and diabetes. We analysed 14 cases of polymorphisms located in 10 candidate loci, in a sample of patients with T2D and controls from Mexico City. METHODS: We analysed the association of 14 polymorphisms located within 10 genes (TCF7L2, ENPP1, ADRB3, KCNJ11, LEPR, PPARgamma, FTO, CDKAL1, SIRT1 and HHEX) with T2D and MS. The analysis included 519 subjects with T2D defined according to the ADA criteria, 389 with MS defined according to the AHA/NHLBI criteria and 547 controls. Association was tested with the program ADMIXMAP including individual ancestry, age, sex, education and in some cases body mass index (BMI), in a logistic regression model. RESULTS: The two markers located within the TCF7L2 gene showed strong associations with T2D (rs7903146, T allele, odd ratio (OR) = 1.76, p = 0.001 and rs12255372, T allele, OR = 1.78, p = 0.002), but did not show significant association with MS. The non-synonymous rs4994 polymorphism of the ADRB3 gene was associated with T2D (Trp allele, OR = 0.62, p = 0.001) and MS (Trp allele, OR = 0.74, p = 0.018). Nominally significant associations were also observed between T2D and the SIRT1 rs3758391 SNP and MS and the HHEX rs5015480 polymorphism. CONCLUSIONS: Variants located within the gene TCF7L2 are strongly associated with T2D but not with MS, providing support to previous evidence indicating that polymorphisms at the TCF7L2 gene increase T2D risk. In contrast, the non-synonymous ADRB3 rs4994 polymorphism is associated with T2D and MS.

[Multiple sclerosis]. / Esclerosis múltiple.

Multiple sclerosis, a neurological problem in which mechanisms of autoimmunity and immunodeficiency may cause damage appears with a variable range of immune response. In this paper we classify in three grate subgroups the alterations observed in our patients: Type I: specific defect of immune response; Type II: immunodeficiency with autoimmune responses; Type III: mixed responses: autoimmunity with specific defect of immune response and increased cytotoxicity. A rational explanation about the various immunological changes emerged from comprehension of these mechanisms of response and following these hypothesis we propose an immunological classification of multiple sclerosis in other to reach more effective therapeutic goals.