Erratum: Gut microbiota composition is associated with the efficacy of Delta-24-RGDOX in malignant gliomas.

[This corrects the article DOI: 10.1016/j.omton.2024.200787.].

Gut microbiota composition is associated with the efficacy of Delta-24-RGDOX in malignant gliomas.

Glioblastoma, the most common primary brain tumor, has a 6.8% survival rate 5 years post diagnosis. Our team developed an oncolytic adenovirus with an OX-40L expression cassette named Delta-24-RGDOX. While studies have revealed the interaction between the gut microbiota and immunotherapy agents, there are no studies linking the gut microbiota with viroimmunotherapy efficacy. We hypothesize that gut bacterial signatures will be associated with oncolytic viral therapy efficacy. To test this hypothesis, we evaluated the changes in gut microbiota in two mouse cohorts: (1) GSC-005 glioblastoma-bearing mice treated orally with indoximod, an immunotherapeutic agent, or with Delta-24-RGDOX by intratumoral injection and (2) a mouse cohort harboring GL261-5 tumors used to mechanistically evaluate the importance of CD4+ T cells in relation to viroimmunotherapy efficacy. Microbiota assessment indicated significant differences in the structure of the gut bacterial communities in viroimmunotherapy-treated animals with higher survival compared with control or indoximod-treated animals. Moreover, viroimmunotherapy-treated mice with prolonged survival had a higher abundance of Bifidobacterium. The CD4+ T cell depletion was associated with gut dysbiosis, lower mouse survival, and lower antitumor efficacy of the therapy. These findings suggest that microbiota modulation along the gut-glioma axis contributes to the clinical efficacy and patient survival of viroimmunotherapy treated animals.

Vaginal Microbiota and HPV in Latin America: A Narrative Review.

With the expansion of human microbiome studies in the last 15 years, we have realized the immense implications of microbes in human health. The human holobiont is now accepted, given the commensal relationships with bacteria, fungi, parasites, viruses, and human cells. The cervicovaginal microbiota is a specific case within the human microbiome where diversity is lower to maintain a chemical barrier of protection against infections. This narrative review focuses on the vaginal microbiome. It summarizes key findings on how native bacteria protect women from disease or predispose them to damaging inflammatory processes with an emphasis on the role of HPV infections in Latin America, one of the world's regions with the highest cervical cancer prevalence.

Exploring the interplay between running exercises, microbial diversity, and tryptophan metabolism along the microbiota-gut-brain axis.

The emergent recognition of the gut-brain axis connection has shed light on the role of the microbiota in modulating the gut-brain axis's functions. Several microbial metabolites, such as serotonin, kynurenine, tryptamine, indole, and their derivatives originating from tryptophan metabolism have been implicated in influencing this axis. In our study, we aimed to investigate the impact of running exercises on microbial tryptophan metabolism using a mouse model. We conducted a multi-omics analysis to obtain a comprehensive insight into the changes in tryptophan metabolism along the microbiota-gut-brain axis induced by running exercises. The analyses integrated multiple components, such as tryptophan changes and metabolite levels in the gut, blood, hippocampus, and brainstem. Fecal microbiota analysis aimed to examine the composition and diversity of the gut microbiota, and taxon-function analysis explored the associations between specific microbial taxa and functional activities in tryptophan metabolism. Our findings revealed significant alterations in tryptophan metabolism across multiple sites, including the gut, blood, hippocampus, and brainstem. The outcomes indicate a shift in microbiota diversity and tryptophan metabolizing capabilities within the running group, linked to increased tryptophan transportation to the hippocampus and brainstem through circulation. Moreover, the symbiotic association between Romboutsia and A. muciniphila indicated their potential contribution to modifying the gut microenvironment and influencing tryptophan transport to the hippocampus and brainstem. These findings have potential applications for developing microbiota-based approaches in the context of exercise for neurological diseases, especially on mental health and overall well-being.

Ecological competition in the oral mycobiome of Hispanic adults living in Puerto Rico associates with periodontitis.

Background: Fungi are a major component of the human microbiome that only recently received attention. The imbalance of indigenous fungal communities and environmental fungi present in the oral cavity may have a role in oral dysbiosis, which could exacerbate oral inflammatory diseases. Methods: We performed a cross-sectional study and recruited 88 participants aged 21 to 49 from sexually transmitted infection clinics in Puerto Rico. A full-mouth periodontal examination following the NHANES protocol defined periodontal severity (CDC/AAP). ITS2 (fungal) genes were amplified and sequenced for mycobiota characterization of yeast and environmental fungi. Environmental outdoor spore levels were measured daily by the American Academy of Allergy Asthma and Immunology San Juan station and defined by quartiles as spore scores. Results: Our data indicate polymicrobial colonization of yeast and environmental fungi in the oral cavity. Dominant taxa associated with periodontal disease included Saccharomyces cerevisiae, Rigidoporus vinctus, and Aspergillus penicilloides, while Candida albicans were found to be ubiquitous. Fungal aerosols were found to impact the oral cavity biofilm, likely due to competition and neutralization by inhaled outdoor and indoor fungal spores. Conclusion: To our knowledge, this is the first report showcasing the ecological competition of measured outdoor environmental fungi with the human oral mycobiota.

Inflammatory cytokines and a diverse cervicovaginal microbiota associate with cervical dysplasia in a cohort of Hispanics living in Puerto Rico.

Cervical cancer (CC) is women's fourth most common cancer worldwide. A worrying increase in CC rates in Hispanics suggests that besides Human papillomavirus infections, there may be other cofactors included in the epithelial microenvironment that could play a role in promoting the disease. We hypothesized that the cervical microbiome and the epithelial microenvironment favoring inflammation is conducive to disease progression in a group of Hispanics attending gynecology clinics in Puerto Rico. Few studies have focused on the joint microbiota and cytokine profile response in Hispanics outside the US, especially regarding the development of precancerous lesions. We aimed to investigate the relationship between the cervicovaginal microbiome and inflammation in Hispanic women living in PR while considering cervical dysplasia and HPV genotype risk. Cervical samples collected from 91 participants coming to gynecology clinics in San Juan, underwent 16S rRNA genes (V4 region) profiling, and cytokines were measured using Luminex MAGPIX technology. Cytokines were grouped as inflammatory (IL-1ß, TNFα, IFNγ, IL-6), anti-inflammatory (IL- 4, IL-10, TGFß1), and traffic-associated (IL-8, MIP1a, MCP1, IP10). They were related to microbes via an inflammation scoring index based on the quartile and tercile distribution of the cytokine's concentration. We found significant differences in the diversity and composition of the microbiota according to HPV type according to carcinogenic risk, cervical disease, and cytokine abundance. Community State Types (CSTs) represents a profile of microbial communities observed within the vaginal microbiome ecological niche, and Lactobacillus-depleted CST IV had ~ 90% dominance in participants with high-grade squamous intraepithelial lesions and high-risk HPV. The increasing concentration of pro-inflammatory cytokines was associated with a decrease in L. crispatus. In contrast, dysbiosis-associated bacteria such as Gardnerella, Prevotella, Atopobium concomitantly increased with pro-inflammatory cytokines. Our study highlights that the cervical microbiota of Hispanics living in Puerto Rico is composed mostly of diverse CST profiles with decreased Lactobacillus and is associated with a higher pro-inflammatory environment. The joint host-microbe interaction analyses via cytokine and microbiota profiling have very good translational potential.

The cervical microbiota of Hispanics living in Puerto Rico is nonoptimal regardless of HPV status.

The cervicovaginal microbiota is influenced by host physiology, immunology, lifestyle, and ethnicity. We hypothesized that there would be differences in the cervicovaginal microbiota among pregnant, nonpregnant, and menopausal women living in Puerto Rico (PR) with and without human papillomavirus (HPV) infection and cervical cancer. We specifically wanted to determine if the microbiota is associated with variations in cervical cytology. A total of 294 women, including reproductive-age nonpregnant (N = 196), pregnant (N = 37), and menopausal (N = 61) women, were enrolled. The cervicovaginal bacteria were characterized by 16S rRNA amplicon sequencing, the HPV was genotyped with SPF10-LiPA, and cervical cytology was quantified. High-risk HPV (HR-HPV, 67.3%) was prevalent, including genotypes not covered by the 9vt HPV vaccine. Cervical lesions (34%) were also common. The cervical microbiota was dominated by Lactobacillus iners. Pregnant women in the second and third trimesters exhibited a decrease in diversity and abundance of microbes associated with bacterial vaginosis. Women in menopause had greater alpha diversity, a greater proportion of facultative and strictly anaerobic bacteria, and higher cervicovaginal pH than premenopausal women. Cervical lesions were associated with greater alpha diversity. However, no significant associations between the microbiota and HPV infection (HR or LR-HPV types) were found. The cervicovaginal microbiota of women living in Puerto Rican were either dominated by L. iners or diverse microbial communities regardless of a woman's physiological stage. We postulate that the microbiota and the high prevalence of HR-HPV increase the risk of cervical lesions among women living in PR. IMPORTANCE In the enclosed manuscript, we provide the first in-depth characterization of the cervicovaginal microbiota of Hispanic women living in Puerto Rico (PR), using a 16S rRNA approach, and include women of different physiological stages. Surprisingly we found that high-risk HPV was ubiquitous with a prevalence of 67.3%, including types not covered by the 9vt HPV vaccine. We also found highly diverse microbial communities across women groups-with a reduction in pregnant women, but dominated by nonoptimal Lactobacillus iners. Additionally, we found vaginosis-associated bacteria as Dialister spp., Gardnerella spp., Clostridium, or Prevotella among most women. We believe this is a relevant and timely article expanding knowledge on the cervicovaginal microbiome of PR women, where we postulate that these highly diverse communities are conducive to cervical disease.

Gut microbiota variation of a tropical oil-collecting bee species far exceeds that of the honeybee.

Introduction: Interest for bee microbiota has recently been rising, alleviating the gap in knowledge in regard to drivers of solitary bee gut microbiota. However, no study has addressed the microbial acquisition routes of tropical solitary bees. For both social and solitary bees, the gut microbiota has several essential roles such as food processing and immune responses. While social bees such as honeybees maintain a constant gut microbiota by direct transmission from individuals of the same hive, solitary bees do not have direct contact between generations. They thus acquire their gut microbiota from the environment and/or the provision of their brood cell. To establish the role of life history in structuring the gut microbiota of solitary bees, we characterized the gut microbiota of Centris decolorata from a beach population in Mayagüez, Puerto Rico. Females provide the initial brood cell provision for the larvae, while males patrol the nest without any contact with it. We hypothesized that this behavior influences their gut microbiota, and that the origin of larval microbiota is from brood cell provisions. Methods: We collected samples from adult females and males of C. decolorata (n = 10 each, n = 20), larvae (n = 4), and brood cell provisions (n = 10). For comparison purposes, we also sampled co-occurring female foragers of social Apis mellifera (n = 6). The samples were dissected, their DNA extracted, and gut microbiota sequenced using 16S rRNA genes. Pollen loads of A. mellifera and C. decolorata were analyzed and interactions between bee species and their plant resources were visualized using a pollination network. Results: While we found the gut of A. mellifera contained the same phylotypes previously reported in the literature, we noted that the variability in the gut microbiota of solitary C. decolorata was significantly higher than that of social A. mellifera. Furthermore, the microbiota of adult C. decolorata mostly consisted of acetic acid bacteria whereas that of A. mellifera mostly had lactic acid bacteria. Among C. decolorata, we found significant differences in alpha and beta diversity between adults and their brood cell provisions (Shannon and Chao1 p < 0.05), due to the higher abundance of families such as Rhizobiaceae and Chitinophagaceae in the brood cells, and of Acetobacteraceae in adults. In addition, the pollination network analysis indicated that A. mellifera had a stronger interaction with Byrsonima sp. and a weaker interaction with Combretaceae while interactions between C. decolorata and its plant resources were constant with the null model. Conclusion: Our data are consistent with the hypothesis that behavioral differences in brood provisioning between solitary and social bees is a factor leading to relatively high variation in the microbiota of the solitary bee.

Design and Implementation of a Culturally-Tailored Randomized Pilot Trial: Puerto Rican Optimized Mediterranean-Like Diet.

Background: Adhering to a Mediterranean Diet (MedDiet) is associated with a healthier cardiometabolic profile. However, there are limited studies on the MedDiet benefits for non-Mediterranean racial/ethnic minorities, for whom this diet may be unfamiliar and inaccessible and who have a high risk of chronic diseases. Objectives: To describe the study design of a pilot trial testing the efficacy of a MedDiet-like tailored to adults in Puerto Rico (PR). Methods: The Puerto Rican Optimized Mediterranean-like Diet (PROMED) was a single-site 4-mo parallel two-arm randomized pilot trial among a projected 50 free-living adults (25-65 y) living in PR with at least two cardiometabolic risk factors (clinicaltrials.gov registration #NCT03975556). The intervention group received 1 individual nutritional counseling session on a portion-control culturally-tailored MedDiet. Daily text messages reinforced the counseling content for 2 mo, and we supplied legumes and vegetable oils. Participants in the control group received cooking utensils and one standard portion-control nutritional counseling session that was reinforced with daily texts for 2 mo. Text messages for each group were repeated for two more months. Outcome measures were assessed at baseline, 2 and 4 m. The primary outcome was a composite cardiometabolic improvement score; secondary outcomes included individual cardiometabolic factors; dietary intake, behaviors, and satisfaction; psychosocial factors; and the gut microbiome. Results: PROMED was designed to be culturally appropriate, acceptable, accessible, and feasible for adults in PR. Strengths of the study include applying deep-structure cultural components, easing structural barriers, and representing a real-life setting. Limitations include difficulty with blinding and with monitoring adherence, and reduced timing and sample size. The COVID-19 pandemic influenced implementation, warranting replication. Conclusions: If PROMED is proven efficacious in improving cardiometabolic health and diet quality, the findings would strengthen the evidence on the healthfulness of a culturally-appropriate MedDiet and support its wider implementation in clinical and population-wide disease-prevention programs.

The Epibiotic Microbiota of Wild Caribbean Sea Urchin Spines Is Species Specific.

Caribbean sea urchins are marine invertebrates that have experienced a decline over the years. Studies on sea urchins have focused primarily on the microbiome of the coelomic fluid or the gut microbiota. In this study, the epibiota community associated with four wild Caribbean sea urchin species, Lytechinus variegatus, Echinometra lucunter, Tripneustes ventricosus, and Diadema antillarum, was characterized for the first time. Using 57 sea urchin animal samples, we evaluated the influence of animal species, trophic niches, and geographical location on the composition of the epibiotic microbiota. We found significant differences in the bacterial biota among species and trophic niches, but not among geographical locations. L. variegatus exhibited the highest alpha diversity with high dominance of Fusobacteria, Planctomycetes, and Cyanobacteria, whereas T. ventricosus and D. antillarum were dominated by Firmicutes. T. ventricosus inhabiting the seagrass biotope dominated by Thalassia testudinum meadows had mostly Endozoicomonas. In contrast, samples located in the reef (dominated by corals and other reef builders) had a higher abundance of Kistimonas and Photobacterium. Our findings confirm that the epibiotic microbiota is species-specific, but also niche-dependent, revealing the trophic networks emerging from the organic matter being recycled in the seagrass and reef niches. As echinoids are important grazers of benthic communities, their microbiota will likely influence ecosystem processes.

Bacterial composition along the digestive tract of the Horned Screamer (Anhima cornuta), a tropical herbivorous bird.

Background: The Horned Screamer (Anhima cornuta) is an herbivorous bird that inhabits wetlands of the South American tropical region. We hypothesize that due to its herbivorous niche, its digestive tract compartments may have bacteria specialized in fermenting complex plant carbohydrates. To test this hypothesis, we compared the bacterial communities along the gastrointestinal tract (GIT) of a Horned Screamer captured in Venezuela. Methods: Samples were taken from tissues and content of the proventriculus and the small intestine (considered for this study as upper GIT), and the large intestine and cecum (lower GIT). The bacterial community was characterized by sequencing the V4 region of the 16S rRNA gene. Bioinformatic analysis was performed using QIIME, QIITA and Microbiome Analyst. The association between microbial taxonomy and function was analyzed using their Greengenes OTU IDs and a custom KEGG BRITE hierarchical tree and visualized with BURRITO. Results: The Screamer's gastrointestinal microbiota was composed by seven phyla being Firmicutes and Bacteroidetes the most predominant. The dominant taxa in the upper GIT were Helicobacter, Vibrio, Enterobacter, Acinetobacter and Staphylococcus. The dominant taxa in the lower GIT were Oribacterium, Blautia, Roseburia, Ruminococcus, Desulfovibrio, Intestinimonas, Marvinbryantia and Parabacteroides. Complete degradation of cellulose to the end-products acetate, propanoate, butanoate and acetoacetate was found in the upper and lower GIT without significant differences. Conclusion: Our study confirmed changes in bacterial community composition throughout the GIT of the Horned Screamer primarily associated with the production of metabolic end-products of carbohydrate digestion essential for the fermentation of the herbivorous diet.

The Microbiome and Mental Health Across the Lifespan.

INTRODUCTION: The combined genetic material of the microorganisms in the human body, known as the microbiome, is being increasingly recognized as a major determinant of human health and disease. Although located predominantly on mucosal surfaces, these microorganisms have profound effects on brain functioning through the gut-brain axis. METHOD: The content of the chapter is based on a study group session at the annual meeting of the American College of Neuropsychopharmacology (ACNP). The objective was to discuss the emerging relationship between the human microbiome and mental health as relevant to ACNP's interests in developing and evaluating novel neuropsychiatric treatment strategies. The focus is on specific brain disorders, such as schizophrenia, substance use, and Alzheimer's disease, as well as on broader clinical issues such as suicidality, loneliness and wisdom in old age, and longevity. RESULTS: Studies of schizophrenia indicate that the microbiome of individuals with this disorder differs from that of non-psychiatric comparison groups in terms of diversity and composition. Differences are also found in microbial metabolic pathways. An early study in substance use disorders found that individuals with this disorder have lower levels of beta diversity in their oral microbiome than a comparison group. This measure, along with others, was used to distinguish individuals with substance use disorders from controls. In terms of suicidality, there is preliminary evidence that persons who have made a suicide attempt differ from psychiatric and non-psychiatric comparison groups in measures of beta diversity. Exploratory studies in Alzheimer's disease indicate that gut microbes may contribute to disease pathogenesis by regulating innate immunity and neuroinflammation and thus influencing brain function. In another study looking at the microbiome in older adults, positive associations were found between wisdom and alpha diversity and negative associations with subjective loneliness. In other studies of older adults, here with a focus on longevity, individuals with healthy aging and unusually long lives had an abundance of specific microorganisms which distinguished them from other individuals. DISCUSSION: Future studies would benefit from standardizing methods of sample collection, processing, and analysis. There is also a need for the standardized collection of relevant demographic and clinical data, including diet, medications, cigarette smoking, and other potentially confounding factors. While still in its infancy, research to date indicates a role for the microbiome in mental health disorders and conditions. Interventions are available which can modulate the microbiome and lead to clinical improvements. These include microbiome-altering medications as well as probiotic microorganisms capable of modulating the inflammation in the brain through the gut-brain axis. This research holds great promise in terms of developing new methods for the prevention and treatment of a range of human brain disorders.

Oral microbiota and periodontitis severity among Hispanic adults.

Background: Periodontitis, one of the most common bacterial infections characterized by chronic inflammation, is also known to be a risk factor for chronic conditions, including cardiovascular disease and cancer. This inflammation is driven by an altered microbiota with an increase in pathogenic bacteria. We evaluated the association between oral microbiota and periodontitis severity in high-risk Hispanics. Method: This cross-sectional study recruited 134 sexually active participants aged 21 to 49 years old from STI Clinics in Puerto Rico. A periodontal examination, saliva collection, and an interviewer-administered questionnaire were performed. Periodontal severity was categorized as: having no disease, mild, and moderate/severe and BOP and tooth loos was noted. Saliva samples were collected for genomic DNA extraction, downstream 16S rDNA amplification sequencing, and bioinformatics analyses. Results: The structure, composition, and diversity of bacterial communities differed significantly according to periodontal severity. The richness and overall diversity also differed between participants without periodontitis and participants with some level of periodontal disease. A higher abundance of Prevotella, Veillonella, or Treponema was attributed to periodontal disease and Aggregatibacter to severe bleeding on probing, while Neisseria was found in higher abundance in healthy participants, decreasing its levels with drinking, smoking, and oral sex practices. Conclusions: Our findings indicate that dysbiosis occurs as periodontal disease progresses, and both alcohol consumption and smoking habits pose risk factors for oral dysbiosis. These results are of public health and clinical impact, as several bacteria identified could serve in the future as biomarkers for periodontitis and oral cancer risk.

Limited microbiome differences in captive and semi-wild primate populations consuming similar diets.

Gut microbial communities are shaped by a myriad of extrinsic factors, including diet and the environment. Although distinct human populations consistently exhibit different gut microbiome compositions, variation in diet and environmental factors are almost always coupled, making it difficult to disentangle their relative contributions to shaping the gut microbiota. Data from discrete animal populations with similar diets can help reduce confounds. Here, we assessed the gut microbiota of free-ranging and captive rhesus macaques with at least 80% diet similarity to test the hypothesis that hosts in difference environments will have different gut microbiomes despite a shared diet. Although we found that location was a significant predictor of gut microbial composition, the magnitude of observed differences was relatively small. These patterns suggest that a shared diet may limit the typical influence of environmental microbial exposure on the gut microbiota.

Prenatal exposure to Hurricane Maria is associated with an altered infant nasal microbiome.

Background: Prenatal adverse exposures have been associated with increased risks of development of respiratory diseases in children. The infant nasal microbiome is an important mechanism and indicator. Objective: Our aim was to characterize and compare the nasal microbiome of infants who were in utero and exposed to Hurricane Maria in Puerto Rico during 2017 with that of infants who were conceived at least 5 months after the hurricane as controls. Methods: We recruited 63 vaginally born infants, 29 of whom were in the exposure group and 34 of whom were in the control group. Nasal swab samples were collected and analyzed by using 16S ribosomal RNA gene sequencing at the community and taxon levels, respectively. Results: Infants in the exposure group were more likely to harbor a Staphylococcus-Streptococcus-dominant microbial community in their nose. The richness and diversity of the microbiome was significantly higher in the exposure group than in the control group. In the exposure group, the bacterial genera Rhodocista, Azospirillum, Massilia, Herbaspirillum, Aquabacterium, and Pseudomonas were enriched, whereas Corynebacterium and Ralstonia were depleted. Food insecurity due to Hurricane Maria was associated with an increase in Pseudomonas in the infant nasal microbiome. Conclusion: Infants who were exposed to Hurricane Maria during gestation had an altered nasal microbiome, with a higher prevalence of environmental bacteria. More research is needed to evaluate the long-term impacts of extreme weather events occurring in the prenatal stage on a child's nasal microbiome and respiratory health.

The Bacterial and Fungal Gut Microbiota of the Greater Wax Moth, Galleria mellonella L. Consuming Polyethylene and Polystyrene.

Plastic production has been increasing exponentially in the last 60 years, but plastic disposal is out of control, resulting in the pollution of all ecosystems on Earth. Finding alternative environmentally sustainable choices, such as biodegradation by insects and their associated gut microbiota, is crucial, however we have only begun to characterize these ecosystems. Some bacteria and one fungus have been previously identified in the gut of Greater Wax Moth larvae (Galleria mellonella L., Lepidoptera, Pyralidae) located mainly in the Northern hemisphere. The aim of this study was to describe changes in the gut microbiota associated with the consumption of polyethylene and polystyrene by the Greater Wax Moth in Argentina, considering both bacteria and fungi. Larvae were fed polyethylene, polystyrene and beeswax as control for 7 days. Next generation sequencing revealed changes in the bacterial gut microbiome of the wax moth larvae at the phyla and genus levels, with an increase in two Pseudomonas strains. The fungal communities showed no differences in composition between diets, only changing in relative abundance. This is the first report of both bacterial and fungal communities associated with a plastivore insect. The results are promising and call for more studies concerning a potential multi-kingdom synergy in the plastic biodegradation process.

Reshaping the tumor microenvironment with oncolytic viruses, positive regulation of the immune synapse, and blockade of the immunosuppressive oncometabolic circuitry.

BACKGROUND: Oncolytic viruses are considered part of immunotherapy and have shown promise in preclinical experiments and clinical trials. Results from these studies have suggested that tumor microenvironment remodeling is required to achieve an effective response in solid tumors. Here, we assess the extent to which targeting specific mechanisms underlying the immunosuppressive tumor microenvironment optimizes viroimmunotherapy. METHODS: We used RNA-seq analyses to analyze the transcriptome, and validated the results using Q-PCR, flow cytometry, and immunofluorescence. Viral activity was analyzed by replication assays and viral titration. Kyn and Trp metabolite levels were quantified using liquid chromatography-mass spectrometry. Aryl hydrocarbon receptor (AhR) activation was analyzed by examination of promoter activity. Therapeutic efficacy was assessed by tumor histopathology and survival in syngeneic murine models of gliomas, including Indoleamine 2,3-dioxygenase (IDO)-/- mice. Flow cytometry was used for immunophenotyping and quantification of cell populations. Immune activation was examined in co-cultures of immune and cancer cells. T-cell depletion was used to identify the role played by specific cell populations. Rechallenge experiments were performed to identify the development of anti-tumor memory. RESULTS: Bulk RNA-seq analyses showed the activation of the immunosuppressive IDO-kynurenine-AhR circuitry in response to Delta-24-RGDOX infection of tumors. To overcome the effect of this pivotal pathway, we combined Delta-24-RGDOX with clinically relevant IDO inhibitors. The combination therapy increased the frequency of CD8+ T cells and decreased the rate of myeloid-derived suppressor cell and immunosupressive Treg tumor populations in animal models of solid tumors. Functional studies demonstrated that IDO-blockade-dependent activation of immune cells against tumor antigens could be reversed by the oncometabolite kynurenine. The concurrent targeting of the effectors and suppressors of the tumor immune landscape significantly prolonged the survival in animal models of orthotopic gliomas. CONCLUSIONS: Our data identified for the first time the in vivo role of IDO-dependent immunosuppressive pathways in the resistance of solid tumors to oncolytic adenoviruses. Specifically, the IDO-Kyn-AhR activity was responsible for the resurface of local immunosuppression and resistance to therapy, which was ablated through IDO inhibition. Our data indicate that combined molecular and immune therapy may improve outcomes in human gliomas and other cancers treated with virotherapy.

Sex and educational attainment differences in HPV knowledge and vaccination awareness among unvaccinated-sexually active adults in Puerto Rico.

Human papillomavirus (HPV) knowledge and HPV vaccination uptake remain suboptimal. We assessed sex and educational attainment differences in HPV knowledge and vaccine awareness. Data from a cross-sectional study (2018-2021) in Puerto Rico among adults aged 21-49 was analyzed (n = 278). Adequate knowledge was defined as a score of ≥70% of correct responses on a 13-item knowledge scale. Multivariable logistic regression was used to assess the association of sex (men vs. women) and education (high school or less vs. more than high school) categories with adequate HPV knowledge and vaccine awareness. Adequate HPV knowledge was higher among women (53%) and men (46%) with more than high school and was lower among women (46%) and men (27%) with high school or less. For HPV vaccine awareness, similar results were observed. Women (OR = 3.0 ; 95%CI = 1.4-6.2) and men (OR = 2.3 , 95%CI = 1.1-4.8) with more than high school and women with high school or less (OR = 2.3 , 95%CI = 1.0-5.2) were more likely to have adequate HPV vaccine knowledge than men with high-school or less education. Heightened HPV vaccine awareness was also seen among more educated women and men and women with similar lower education when compared to men with ≤ high school. Men and individuals with lower educational attainment were more likely to have inadequate HPV knowledge and vaccine awareness. HPV vaccine-oriented educational interventions should target these high-risk groups.

The Gut Microbiome May Help Address Mental Health Disparities in Hispanics: A Narrative Review.

The gut-brain axis is the biological connection between the enteric and the central nervous systems. Given the expansion of the microbial sciences with the new human microbiome field facilitated by the decrease in sequencing costs, we now know more about the role of gut microbiota in human health. In this short review, particular focus is given to the gut-brain axis and its role in psychiatric diseases such as anxiety and depression. Additionally, factors that contribute to changes in the gut-brain axis, including the gut microbiome, nutrition, the host's genome, and ethnic difference, are highlighted. Emphasis is given to the lack of studies on Hispanic populations, despite the fact this ethnic group has a higher prevalence of anxiety and depression in the US.

Hurricane María drives increased indoor proliferation of filamentous fungi in San Juan, Puerto Rico: a two-year culture-based approach.

Extensive flooding caused by Hurricane María in Puerto Rico (PR) created favorable conditions for indoor growth of filamentous fungi. These conditions represent a public health concern as contamination by environmental fungi is associated with a higher prevalence of inflammatory respiratory conditions. This work compares culturable fungal spore communities present in homes that sustained water damage after Hurricane María to those present in dry, non-flooded homes. We collected air samples from 50 houses in a neighborhood in San Juan, PR, 12 and 22 months after Hurricane María. Self-reported data was used to classify the homes as flooded, water-damage or dry non-flooded. Fungi abundances, composition and diversity were analyzed by culturing on two media. Our results showed no significant differences in indoor fungal concentrations (CFU/m3) one year after the Hurricane in both culture media studied (MEA and G25N). During the second sampling period fungal levels were 2.7 times higher in previously flooded homes (Median = 758) when compared to dry homes (Median = 283), (p-value < 0.005). Fungal profiles showed enrichment of Aspergillus species inside flooded homes compared to outdoor samples during the first sampling period (FDR-adjusted p-value = 0.05). In contrast, 22 months after the storm, indoor fungal composition consisted primarily of non-sporulated fungi, most likely basidiospores, which are characteristic of the outdoor air in PR. Together, this data highlights that homes that suffered water damage not only have higher indoor proliferation of filamentous fungi, but their indoor fungal populations change over time following the Hurricane. Ultimately, after nearly two years, indoor and outdoor fungal communities converged in this sample of naturally ventilated homes.