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Arrieta, M. C.

Publications and source records attributed to Arrieta, M. C..

5 recordsLinked to original sources

Early-life gut microbiome and stress-axis perturbations dysregulate systemic, mucosal, and brain immunity

BackgroundEarly-life disruptions to the gut microbiome and stress-axis significantly influence the development of immune, neuroendocrine, and other physiological systems. However, the precise microbial species and pathways mediating these effects remain poorly characterized. Using a murine model, we investigated the individual and combined effects of early-life antibiotic exposure and chronic stress on gut microbiota composition, short-chain fatty acid (SCFA) production, hypothalamic-pituitary-adrenal (HPA) axis activity, and systemic, mucosal, and neuroimmune responses. ResultsBroad-spectrum antibiotic treatments severely reduced microbial diversity and SCFA concentrations, with changes persisting into adulthood. Chronic early-life stress exerted more modest but notable effects, reducing key SCFA-producing taxa and impacting microbiome metabolic output. Combined disruptions led to altered microglial active phenotype and cytokine profiles, impaired immune cell populations, and suppressed HPA axis activity. Multi-omic correlational analyses revealed strong associations between SCFAs, specific gut microbes, and immune responses, implicating SCFAs as critical mediators of gut-brain communication. Notably, antibiotic exposure exacerbated susceptibility to allergic airway inflammation, highlighting the systemic consequences of early-life microbiome disturbances. ConclusionsThese findings demonstrate that early microbial perturbations impair neuroimmune maturation, HPA axis regulation, and host resilience to inflammatory diseases. Our study underscores the importance of preserving the early-life microbiome to support long-term immune and neurodevelopmental health, offering insights into potential therapeutic interventions for mitigating the impact of early-life microbiota disruptions.

microbiology↗

Antibiotic-induced Malassezia spp. expansion in infants promotes early-life immune dysregulation and airway inflammation in mice

Antibiotics have deleterious consequences for the gut microbiome and can increase the risk of childhood asthma. While the effects of antibiotics on the bacterial microbiome and asthma risk are well characterized, their impact on the fungal microbiome (mycobiome) remains vastly unexplored. We investigated the effect of antibiotic use on the gut mycobiome in an observational, prospective clinical study of young infants. Antibiotic treatment resulted in increased fungal abundance and expansion of the yeast Malassezia spp. Based on these findings, germ-free mouse pups were colonized with a defined consortium of mouse-derived bacteria (Oligo-MM12) with or without Malassezia restricta. Colonization with this yeast increased myeloid and lymphoid intestinal immune responses deemed critical in atopy development, and elevated airway inflammation in house-dust mite (HDM)-challenged mice. Further evaluation in eosinophil-deficient mice revealed that the observed immune response is partially dependent on this cell type. This translational work demonstrates that fungal overgrowth and expansion of Malassezia spp. are previously overlooked collateral effects of infant antibiotic use, which may offer a potential strategy to prevent or mitigate pediatric asthma and related conditions. One Sentence Summary: Antibiotic-induced Malassezia spp. expansion in infants promotes early-life immune dysregulation and airway inflammation in gnotobiotic mice.

immunology↗

Cervical Squamous Intraepithelial Lesions are Associated with Changes in the Vaginal Microbiota of Mexican Women

Cervical cancer is an important health concern worldwide and is one of the leading causes of deaths in Mexican women. Previous studies have shown changes in the female genital tract microbe community related to Human Papillomavirus (HPV) infection and cervical cancer, yet this link remains unexplored in many human populations. This study evaluated the vaginal bacterial community among Mexican women with pre-cancerous Squamous Intraepithelial Lesions (SIL). We sequenced the V3 region of the 16S rRNA gene (Illumina Miseq) in cervical samples from 300 Mexican women, including 157 patients with SIL, most of which were HPV positive, and 143 healthy women without HPV infection or SIL. Beta-diversity analysis showed that 14.6% of the variance in vaginal bacterial community structure is related to the presence of SIL. Presence of SIL was also associated with a higher species richness (Chao 1). MaAsLiN analysis yielded independent associations between SIL/HPV status and an increase in the relative abundance Brachybacterium conglomeratum, as well as a decrease in Sphingobium yanoikuyae and Lactobacillus spp. We also identified independent associations between HPV-16, the most common HPV subtype linked to SIL, and Brachybacterium conglomeratum. Our work indicates that the presence of SIL and HPV infection is associated with important changes in the vaginal microbiome, some of which may be specific to this human population. IMPORTANCEHPV plays a critical role in cervical carcinogenesis but is not sufficient for cervical cancer development, indicating involvement of other factors. Vaginal microbiota is an important factor in controlling infections caused by HPV and depending on its composition it can modulate the microenvironment in vaginal mucosa against viral infection. Ethnic and sociodemographic factors influence differences in vaginal microbiome composition, which underlies the dysbiotic patterns linked to HPV infection and cervical cancer across different women populations. Here, we provide evidence for associations between vaginal microbiota patterns and HPV infection, linked to ethnic and sociodemographic factor. To our knowledge, this is the first report of Brevibacterium aureum and Brachybacterium conglomeratum species linked to HPV infection or SIL.

microbiology↗

Metaproteomic Profiling of Fungal Gut Colonization in Gnotobiotic Mice

Eukaryotic microbes can modulate mammalian host health and disease states, yet the molecular contribution of gut fungi remains nascent. We previously showed that mice exclusively colonized with fungi displayed increased sensitivity to allergic airway inflammation and fecal metabolite profiles similar to germ-free mice. To gain insights into the functional changes attributed to fungal colonization, we performed quantitative proteomic analyses of feces and small intestine of four-week-old gnotobiotic mice colonized with bacteria, fungi, or both. A comparison of fecal metaproteomic profiles between the mouse groups yielded broad changes in the relative levels of bacterial (46% of 2,860) and mouse (76% from 405) proteins. Many of the detected fungal proteins (3% of 1,492) have been previously reported as part of extracellular vesicles and having immunomodulating properties. Changes in the levels of mouse proteins derived from the jejunum (4% of 1,514) were mainly driven by proteins functional in lipid metabolism and apoptosis. Using metaproteomic profiling of gnotobiotic conditions, we show that fungal colonization profoundly impacts the host gut proteome. Our results suggest that an increased abundance of certain gut fungal species in early life may impact the developing intracellular balance of epithelial and immune cells.

microbiology↗

Exposure to parasitic protists and helminths changes the intestinal community structure of bacterial microbiota but not of eukaryotes in a cohort of mother-child binomial from a semi-rural setting in Mexico

Around 3.5 billion people are colonized by intestinal parasites worldwide. Intestinal parasitic eukaryotes interact not only with the host, but also with the intestinal microbiota. In this work, we studied the relationship between the presence of multiple enteric parasites and the community structure of the bacterial and eukaryote intestinal microbiota in an asymptomatic cohort of mother-child binomials from a semi-rural community in Mexico. The intestinal parasites identified were Blastocystis hominis, Entamoeba histolytica/dispar, Endolimax nana, Chilomastix mesnili, Iodamoeba butshlii, Entamoeba coli, Hymenolepis nana and Ascaris lumbricoides. We sequenced bacterial 16S rDNA and eukaryotic 18S rDNA in fecal samples of 46 mothers and their respective children, with ages ranging from two to twenty months. Although we did not find significant alpha-diversity changes, we found a significant effect of parasite exposure on bacterial beta-diversity, which explained between 5.2% and 15.0% of the variation of the bacterial community structure. Additionally, exposure to parasites was associated with significant changes in relative abundances of bacterial taxa, characterized by increases in the Clostridia and decreased Actinobacteria and Bacteroidia abundances. There were no significant changes of intestinal microeukaryote abundances associated with parasite exposure. However, we found several significant positive correlations between intestinal bacteria and eukaryotes, including co-occurrence of the fungi Candida tropicalis with Bacteroides and Actinomyces, and Saccharomycetales with Bifidobacterium and Prevotella copri. These bacterial community structure changes associated with parasite exposure imply effects on microbial metabolic routes, host nutrient uptake abilities and intestinal immunity regulation in host-parasite interactions.\n\nIMPORTANCEThe impact of intestinal eukaryotes on the prokaryotic microbiome composition of asymptomatic carriers has not been extensively explored, especially in children and in hosts with multiple parasites. In this work, we studied the relationship between protist and helminth parasite colonization and intestinal microbiota structure in an asymptomatic population of mother-child binomials from the semi-rural community of Morelos in Mexico. We found that the presence of parasitic eukaryotes correlated with changes in the bacterial community structure in the intestinal microbiota in an age-dependent way. This was characterized by an increase of the relative abundance of the class Clostridia and the decrease of Actinobacteria and Bacteroidia. While there were no significant associations between the presence of parasites and microeukaryote community structure, we observed strong positive correlations between bacterial and eukaryote taxa, identifying novel relationships between prokaryotes and fungi, and reflecting the diet of the human population studied.

microbiology↗