Alteration of Gut Microbiota Composition in the Progression of Liver Damage in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex disorder whose prevalence is rapidly growing in South America. The disturbances in the microbiota-gut-liver axis impact the liver damaging processes toward fibrosis. Gut microbiota status is shaped by dietary and lifestyle factors, depending on geographic location. We aimed to identify microbial signatures in a group of Chilean MASLD patients. Forty subjects were recruited, including healthy controls (HCs), overweight/obese subjects (Ow/Ob), patients with MASLD without fibrosis (MASLD/F-), and MASLD with fibrosis (MASLD/F+). Both MASLD and fibrosis were detected through elastography and/or biopsy, and fecal microbiota were analyzed through deep sequencing. Despite no differences in α- and ß-diversity among all groups, a higher abundance of Bilophila and a lower presence of Defluviitaleaceae, Lachnospiraceae ND3007, and Coprobacter was found in MASLD/F- and MASLD/F+, compared to HC. Ruminococcaceae UCG-013 and Sellimonas were more abundant in MASLD/F+ than in Ow/Ob; both significantly differed between MASLD/F- and MASLD/F+, compared to HC. Significant positive correlations were observed between liver stiffness and Bifidobacterium, Prevotella, Sarcina, and Acidaminococcus abundance. Our results show that MASLD is associated with changes in bacterial taxa that are known to be involved in bile acid metabolism and SCFA production, with some of them being more specifically linked to fibrosis.

Amerindian ancestry proportion as a risk factor for inflammatory bowel diseases: results from a Latin American Andean cohort.

Background and aims: Latin American populations remain underrepresented in genetic studies of inflammatory bowel diseases (IBDs). Most genetic association studies of IBD rely on Caucasian, African, and Asian individuals. These associations have yet to be evaluated in detail in the Andean region of South America. We explored the contribution of IBD-reported genetic risk variants to a Chilean cohort and the ancestry contribution to IBD in this cohort. Methods: A total of 192 Chilean IBD patients were genotyped using Illumina's Global Screening Array. Genotype data were combined with similar information from 3,147 Chilean controls. The proportions of Aymara, African, European, and Mapuche ancestries were estimated using the software ADMIXTURE. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for gender, age, and ancestry proportions. We also explored associations with previously reported IBD-risk variants independently and in conjunction with genetic ancestry. Results: The first and third quartiles of the proportion of Mapuche ancestry in IBD patients were 24.7 and 34.2%, respectively, and the corresponding OR was 2.30 (95%CI 1.52-3.48) for the lowest vs. the highest group. Only one variant (rs7210086) of the 180 reported IBD-risk SNPs was associated with IBD risk in the Chilean cohort (adjusted P = 0.01). This variant is related to myeloid cells. Conclusion: The type and proportion of Native American ancestry in Chileans seem to be associated with IBD risk. Variants associated with IBD risk in this Andean region were related to myeloid cells and the innate immune response.

Genotype Prevalence of Lactose Deficiency, Vitamin D Deficiency, and the Vitamin D Receptor in a Chilean Inflammatory Bowel Disease Cohort: Insights from an Observational Study.

Lactose intolerance (LI) and vitamin D deficiency (VDD) have been linked to inflammatory bowel disease (IBD). We conducted an observational study in 192 Chilean IBD patients to investigate the prevalence of a specific gene variant (LCT-13910 CC genotype) associated with LI and the prevalence of VDD/Vitamin D Receptor (VDR) gene variants. Blood samples were analyzed using Illumina's Infinium Global Screening Array. The LCT-13910 CC genotype was found in 61% of IBD patients, similar to Chilean Hispanic controls and lower than Chilean Amerindian controls. The frequency of the LCT-13910-C allele in Chilean IBD patients (0.79) was comparable to the general population and higher than Europeans (0.49). Regarding VDR and VDD variants, in our study, the rs12785878-GG variant was associated with an increased risk of IBD (OR = 2.64, CI = 1.61-4.32; p-value = 0.001). Sixty-one percent of the Chilean IBD cohort have a genetic predisposition to lactose malabsorption, and a significant proportion exhibit genetic variants associated with VDD/VDR. Screening for LI and VDD is crucial in this Latin American IBD population.

Modulation of Postprandial Plasma Concentrations of Digestive Hormones and Gut Microbiota by Foods Containing Oat ß-Glucans in Healthy Volunteers.

Cereal ß-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 ß-glucan from oats (5.2 g). Compared to the control, ß-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). ß-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 ß-glucan for 3 weeks; stools were collected before/after treatment. No changes in fecal microbiota composition/diversity (deep sequencing) were detected with ß-glucans. These results indicate that acute intake of 5 g ß-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 ß-glucan is not sufficient to have an effect on fecal microbiota composition.

Polymorphisms in Schizophrenia-Related Genes Are Potential Predictors of Antipsychotic Treatment Resistance and Refractoriness.

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 SZ 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, to our knowledge, in our admixed Chilean population to address the complete treatment response spectrum. We identified SNPs predictive of treatment-resistant SZ in the genes OXT, CNR1, DDC, and DRD2.

The Firmicutes/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients?

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.

SERT and BDNF polymorphisms interplay on neuroticism in borderline personality disorder.

OBJECTIVE: Genetic factors underlying different personality traits are not entirely understood, particularly how genes interact to modulate their effect. We studied 76 patients diagnosed with borderline personality disorder (BPD), characterized by extreme levels of personality traits, especially neuroticism (N), in which we genotyped two polymorphisms, the 5HTTLPR of the Serotonin transporter (SERT) gene, and the Val66Met of the Brain-derived neurotrophic factor (BDNF) gene. RESULTS: We found an association with SERT, where S-allele carriers had significantly higher levels of N than L-homozygous. Furthermore, we found that the protective effect of L-homozygosity is only evident on A-allele carriers of the BDNF Val66Met polymorphism. Genetic constitution in SERT and BDNF seems to be important in neuroticism, the most relevant personality trait on BPD.