The gut microbiota is emerging as a promising target for the management or prevention of inflammatory and metabolic disorders in humans. Many of the current research efforts are focused on the identification of specific microbial signatures, more particularly for those associated with obesity, type 2 diabetes, and cardiovascular diseases. Some studies have described that the gut microbiota of obese animals and humans exhibits a higher Firmicutes/Bacteroidetes ratio compared with normal-weight individuals, proposing this ratio as an eventual biomarker. Accordingly, the Firmicutes/Bacteroidetes ratio is frequently cited in the scientific literature as a hallmark of obesity. The aim of the present review was to discuss the validity of this potential marker, based on the great amount of contradictory results reported in the literature. Such discrepancies might be explained by the existence of interpretative bias generated by methodological differences in sample processing and DNA sequence analysis, or by the generally poor characterization of the recruited subjects and, more particularly, the lack of consideration of lifestyle-associated factors known to affect microbiota composition and/or diversity. For these reasons, it is currently difficult to associate the Firmicutes/Bacteroidetes ratio with a determined health status and more specifically to consider it as a hallmark of obesity.

Background Approximately 30% of individuals with schizophrenia (SZ) are resistant to conventional antipsychotic drug therapy (AP). Of these, one third are also resistant to the second-line treatment, clozapine. Treatment resistance and refractoriness are associated with increased morbidity and disability, making timely detection of these issues critical. Variability in treatment responsiveness is partly genetic, but research has yet to identify variants suitable for personalizing antipsychotic prescriptions. Methods We evaluated potential associations between response to AP and candidate gene variants previously linked to schizophrenia or treatment response. Two groups of patients with SZ were evaluated; one receiving clozapine (n=135) and the other receiving another second-generation AP (n=61). Single-nucleotide polymorphisms (SNPs) in the genes OXT, OXTR, CNR1, DDC, and DRD2 were analyzed. Results Several SNPs were associated with response vs. resistance to AP or clozapine. Conclusions This is the first study of its kind in our admixed Chilean population to address the complete treatment response spectrum. We identified SNPs predictive of treatment-resistant schizophrenia in the genes OXT, CNR1, DDC, and DRD2.

Cereal β-glucans are beneficial health ingredients that reduce cholesterolemia and postprandial glycaemia. However, their impact on digestive hormones and gut microbiota is not yet fully established. Two randomized, double-blind, controlled studies were conducted. In the first study, 14 subjects ingested a breakfast with or without β-glucan from oats (5.2 g). Compared to the control, β-glucan increased orocecal transit time (p = 0.028) and decreased mean appetite score (p = 0.014) and postprandial plasma ghrelin (p = 0.030), C-peptide (p = 0.001), insulin (p = 0.06), and glucose (p = 0.0006). β-glucan increased plasma GIP (p = 0.035) and PP (p = 0.018) without affecting leptin, GLP-1, PYY, glucagon, amylin, or 7α-hydroxy-4-cholesten-3-one, a biomarker of bile acid synthesis. In the second study, 32 subjects were distributed into 2 groups to ingest daily foods with (3 g/day) or without β-glucan for 3 weeks; stools were collected before/after treatment. No changes in fecal microbiota composition/diversity (deep sequencing) were detected with β-glucans. These results indicate that acute intake of 5 g β-glucan slows transit time and decreases hunger sensation and postprandial glycaemia without affecting bile-acid synthesis, these changes being associated with decreased plasma insulin, C-peptide, and ghrelin, and increased plasma GIP and PP. However, regular daily intake of 3 g β-glucan is not sufficient to have an effect on fecal microbiota composition.

Background Genome-wide association studies (GWAS) have identified hundreds of polymorphisms associated with an increased risk of developing IBD. Among risk genes identified by GWAS, CARD9, a gene encoding an adapter molecule involved in the innate immune response to fungi and bacteria, has been related to IBD risk. CARD9 alleles in IBD patients may have either a protective function or a high genetic risk factor such as rs4077515. Interestingly, the CARD9S12N (rs4077515) variant has a higher frequency in the Latin South American population than the Caucasian population. The relevance of rs4077515 in the risk of IBD in the Latino population is unknown. Aims (1) To estimate allele and genotype frequencies for rs4077515 in IBD patients and Chilean controls and compare with Ensembl genome database (public data available). (2) To compare the allele and genotype distributions in IBD patients and controls, including association tests and estimation of ORs according to additive, dominant and recessive penetrance models. Methods 260 IBD patients were genotyped using the TaqMan SNP genotyping technology based on qPCR. Aggregated genotype information for 3147 population-based Chilean controls was retrieved from a published study on gallstones in Chileans (Lorenzo et al., Hepatology 2021). We calculated the allele and genotype frequencies for rs4077515 and then compared these frequencies with controls. A Chi-square test of association was used under the null hypothesis of no association between genotypes and disease. Univariate and multiple logistic regression were performed (additive, dominant, and recessive penetrance models). Results Table 1 compares rs4077515 allele and genotype frequencies in Chileans and other populations (Ensembl data set). Table 2. exhibits the estimated odds ratio for IBD, CD, and UC in Chilean population. Table 3. reveals the association results for rs4077151 models in the Chilean population. Conclusion In this study, the A risk allele for rs4077515 is significantly more frequent in the Chilean population than reported in other populations such as European, but similar to Amerindian. In this Chilean cohort, the variant rs4077515 is not associated with higher IBD risk. However, this could be an effect of sample size, or patients carrying rs4077515 requires an additional factor to IBD development.

Background IBD has emerged as a worldwide disease with an increased incidence in newly industrialized countries such as Chile. This population has been underrepresented in genome-wide association studies (GWAS) because IBD genetics studies have focused mainly on North America and European populations. In addition, specific IBD risk alleles have been related to different races and ethnicities. Aim: To investigate the association of IBD risk variants reported in previous GWAS studies with clinical outcomes in our Chilean patients. Methods 192 Chilean individuals with IBD (145 UC and 47 CD) were genotyped using Illumina GSA Arrays. From IBD GWAS (Jostin et al. and Liu et al.), we selected gene variants with pGWAS value < 5x10-8 and looked for them in our Chilean IBD group. Then, we built a Chilean dataset (clinical-genotype information). Using this dataset, we performed a Spearman correlation matrix to correlate clinical outcomes with IBD variants. Further, we built regression models to predict the clinical outcomes using the variants obtained from the correlation matrix (p <0.05). Then, we selected the best models using significance testing (P values) or likelihood-based information criterion, such as the Akaike Information Criterion (AIC) and plotted the models using a Receiver Operating Characteristic Curve (ROC). Finally, to evaluate the association among variants in each model, we perform a Gene Ontology biological process enrichment analysis using PANTHER (Fisher, FDR). Results As shown in Figure 1 and Table 1, the best predictive regression models (more than 80%) for the clinical outcomes were surgery, Clinical/Endoscopy remission for more than five years, and Naïve anti-TNF. Association with genetic variants was observed significantly (p<0.05) in the enrichment analysis for the model Clinical/endoscopy remission (Table 2). Conclusion Conclusion. Candidates' genes related to clinical outcomes in our Chilean IBD cohort were related to epithelial, innate, and adaptative immune responses and host-microbial interactions. Future research is needed to validate these findings.