Characterization of gut microbiome profile in children with confirmed wheat allergy.

BACKGROUND: Food allergies pose serious health risks, including life-threatening anaphylactic reactions, increased morbidity, and reduced quality of life. Wheat allergy is a common concern in Asia. There is growing interest in understanding the potential association between dysregulation of the gut microbiome and the development of food allergies. OBJECTIVE: This study aimed to explore the gut microbiome of Thai children with wheat allergy and its potential association with allergic responses. METHODS: Microbial abundance was assessed using Quantitative Insights into Microbial Ecology 2 (QIIME2) microbiome analysis based on 16S rDNA data. The correlation between microbial richness and relevant parameters was evaluated using the Spearman correlation analysis. Additionally, the microbial community functions were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2). RESULTS: The gut microbiome analysis revealed significant differences between the two groups at the phylum and genus levels. Firmicutes (p = 0.012) and Verrucomicrobia (p < 0.001) were enriched in wheat-allergic children, whereas specific gut microbes such as Megamonas (p = 0.04), Romboutsia (p < 0.001), Fusobacterium (p < 0.001), Clostridium senso stricto1 (p < 0.001), and Turicibacter (p < 0.001) were more abundant in healthy children. Anaerostripes (p = 0.011), Erysipelatoclostridium (p < 0.001), Prevotella 2 (p < 0.001), Ruminiclostridium 5 (p < 0.001), and Clostridium innnocuum (p < 0.001) were enriched in children with a confirmed wheat allergy. Functional analysis indicated disparities in the pathways related to arginine and polyamine biosynthesis. CONCLUSION: These findings offer valuable insights into the gut microbiome of children with wheat allergy and its potential impact on symptom severity, laying the groundwork for further research and interventions aimed at addressing this health concern.

Association between Gut Microbiota with Mild Cognitive Impairment and Alzheimer's Disease in a Thai Population.

BACKGROUND: Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are common in older adults. Much recent work has implicated the connection between the gut and the brain via bidirectional communication of the gastrointestinal tract and the central nervous system through biochemical signaling. Altered gut microbiota composition has shown controversial results based on geographic location, age, diet, physical activity, psychological status, underlying diseases, medication, and drug use. OBJECTIVES: This study aimed to investigate the relationships of gut microbiota with MCI and AD. METHODS: 16S metagenome profiles from stool collection of participant groups (normal; n = 20, MCI; n = 12, AD; n = 20) were analyzed. The diagnosis of cognitive conditions was made by standard criteria consisting of clinical interviews, physical examinations, cognitive assessments, laboratory examinations, and neuroimaging by both structural neuroimaging and amyloid positron emission tomography scans. Correlations between medical factors with food frequency and the fecal microbiome were elucidated. RESULTS: A significant difference at the operational taxonomic unit level was observed. The significantly higher abundance of bacteria in nondementia patients belonged to the Clostridiales order, including Clostridium sensu stricto 1 (p < 0.0001), Fusicatenibacter (p = 0.0007), Lachnospiraceae (p = 0.001), Agathobacter (p = 0.021), and Fecalibacterium (p < 0.0001). In contrast, Escherichia-Shigella (p = 0.0002), Bacteroides (p = 0.0014), Holdemanella (p < 0.0001), Romboutsia (p = 0.001), and Megamonas (p = 0.047) were the dominant genera in the AD group. Left and right hippocampus and right amygdala volumes were significantly decreased in the AD group (p < 0.001) and significantly correlated with the groups of bacteria that were significantly different between groups. CONCLUSION: There was a relationship between the composition of the gut microbiome and neurodegenerative disorders, including MCI and AD. Reduction of Clostridiaceae and increases in Enterobacteriaceae and Bacteroides were associated with persons with MCI and AD, consistent with previous studies. The altered gut microbiome could be potentially targeted for the early diagnosis of dementia and the reduction of AD risk.

Tight regulation of the unfolded protein sensor Ire1 by its intramolecularly antagonizing subdomain.

Accumulation of unfolded proteins in the endoplasmic reticulum (ER) accompanies ER stress and causes the type-I transmembrane protein Ire1 (also known as ERN1) to trigger the unfolded protein response (UPR). When dimerized, the core stress-sensing region (CSSR) of Ire1 directly captures unfolded proteins and forms a high-order oligomer, leading to clustering and activation of Ire1. The CSSR is N-terminally flanked by an intrinsically disordered subdomain, which we previously named Subregion I, in Saccharomyces cerevisiae Ire1. In this study, we describe tight repression of Ire1 activity by Subregion I under conditions of no or weak stress. Weak hyperactivation of an Ire1 mutant lacking Subregion I slightly retarded growth of yeast cells cultured under unstressed conditions. Fungal Ire1 orthologs and the animal Ire1 family protein PERK (also known as EIF2AK3) carry N-terminal intrinsically disordered subdomains with a similar structure and function to that of Subregion I. Our observations presented here cumulatively indicate that Subregion I is captured by the CSSR as an unfolded protein substrate. This intramolecular subdomain interaction is likely to compromise self-association of the CSSR, explaining why Subregion I can suppress Ire1 activity when ER-accumulated unfolded proteins are not abundant.