Gonadal sex and chromosome complement influence the gut microbiome in a mouse model of allergic airway inflammation.

Evidence abounds that gut microbiome components are associated with sex disparities in the immune system. However, it remains unclear whether the observed sex disparity in asthma incidence is associated with sex-dependent differences in immune-modulating gut microbiota, and/or its influence on allergic airway inflammatory processes. Using a mouse model of house dust mite (HDM)-induced allergic inflammation and the four core genotypes (FCGs) model, we have previously reported sex differences in lung inflammatory phenotypes. Here, we investigated associations of gut microbiomes with these phenotypes by challenging FCG mice [mouse with female sex chromosome and male gonad (XXM), mouse with female sex chromosome and female gonad (XXF), mouse with male sex chromosome and male gonad (XYM), and mouse with male sex chromosome and female gonad (XYF); n = 7/group] with HDM (25 µg) or PBS intranasally for 5 wk and collecting fecal samples. We extracted fecal DNA and analyzed the 16S microbiome via Targeted Metagenomic Sequencing. We compared α and ß diversity across genotypes and assessed the Firmicutes/Bacteroidetes (F/B) ratio. When comparing baseline and after exposure for the FCG, we found that the gut F/B ratio was only increased in the XXM genotype. We also found that α diversity was significantly increased in all FCG mice upon HDM challenge, with the highest increase in the XXF, and the lowest in the XXM genotypes. Similarly, ß diversity of the microbial community was also affected by challenge in a gonad- and chromosome-dependent manner. In summary, our results indicated that HDM treatment, gonads, and sex chromosomes significantly influence the gut microbial community composition. We concluded that allergic lung inflammation may be affected by the gut microbiome in a sex-dependent manner involving both hormonal and genetic influences.NEW & NOTEWORTHY Recently, the gut microbiome and its role in chronic respiratory disease have been the subject of extensive research and the establishment of its involvement in immune functions. Using the FCG mouse model, our findings revealed the influence of gonads and sex chromosomes on the microbial community structure before and after exposure to HDM. Our data provide a potential new avenue to better understand mediators of sex disparities associated with allergic airway inflammation.

Screening, Brief Intervention, Referral to Treatment Training for Undergraduate Nursing Students: A Quasi-Experimental Comparison of Distance and Face-to-Face Learning.

Alcohol and drug misuse continue to result in negative outcomes in the United States. Training nurses in screening, brief intervention, and referral to treatment (SBIRT) has been proposed as one approach to mitigating those harms. Such training can lead to improved attitudes and intention to use SBIRT in clinical practice, but whether those outcomes manifest similarly for distance or face-to-face learning has not been investigated. The current study is a quasi-experimental comparison of face-to-face and distance SBIRT education for undergraduate nursing students performed in Fall 2019. No differences in attitudes or intentions were observed between face-to-face and distance learning approaches. Self-reported competence meaningfully increased in both study arms, and there was some evidence of additional increases in perceived role legitimacy and intention to use SBIRT. To the degree that benefits are observed for SBIRT training, they may not vary between face-to-face and distance learning implementations of the same curriculum. [Journal of Psychosocial Nursing and Mental Health Services, 60(8), 46-51.].

Developmental bias in horned dung beetles and its contributions to innovation, adaptation, and resilience.

Developmental processes transduce diverse influences during phenotype formation, thereby biasing and structuring amount and type of phenotypic variation available for evolutionary processes to act on. The causes, extent, and consequences of this bias are subject to significant debate. Here we explore the role of developmental bias in contributing to organisms' ability to innovate, to adapt to novel or stressful conditions, and to generate well integrated, resilient phenotypes in the face of perturbations. We focus our inquiry on one taxon, the horned dung beetle genus Onthophagus, and review the role developmental bias might play across several levels of biological organization: (a) gene regulatory networks that pattern specific body regions; (b) plastic developmental mechanisms that coordinate body wide responses to changing environments and; (c) developmental symbioses and niche construction that enable organisms to build teams and to actively modify their own selective environments. We posit that across all these levels developmental bias shapes the way living systems innovate, adapt, and withstand stress, in ways that can alternately limit, bias, or facilitate developmental evolution. We conclude that the structuring contribution of developmental bias in evolution deserves further study to better understand why and how developmental evolution unfolds the way it does.

(My Microbiome) Would Walk 10,000 miles: Maintenance and Turnover of Microbial Communities in Introduced Dung Beetles.

Host-associated microbes facilitate diverse biotic and abiotic interactions between hosts and their environments. Experimental alterations of host-associated microbial communities frequently decrease host fitness, yet much less is known about if and how host-microbiome interactions are altered by natural perturbations, such as introduction events. Here, we begin to assess this question in Onthophagus dung beetles, a species-rich and geographically widely distributed genus whose members rely on vertically transmitted microbiota to support normal development. Specifically, we investigated to what extent microbiome community membership shifts during host introduction events and the relative significance of ancestral associations and novel environmental conditions in the structuring of microbial communities of introduced host species. Our results demonstrate that both evolutionary history and local environmental forces structure the microbial communities of these animals, but that their relative importance is shaped by the specific circumstances that characterize individual introduction events. Furthermore, we identify microbial taxa such as Dysgonomonas that may constitute members of the core Onthophagus microbiome regardless of host population or species, but also Wolbachia which associates with Onthophagus beetles in a species or even population-specific manner. We discuss the implications of our results for our understanding of the evolutionary ecology of symbiosis in dung beetles and beyond.

Microbiome-driven alterations in metabolic pathways and impaired cognition in aged female TgF344-AD rats.

Alzheimer's disease (AD) not only affects cognition and neuropathology, but several other facets capable of negatively impacting quality of life and potentially driving impairments, including altered gut microbiome (GMB) composition and metabolism. Aged (20 + mo) female TgF344-AD and wildtype rats were cognitively characterized on several tasks incorporating several cognitive domains, including task acquisition, object recognition memory, anxiety-like behaviors, and spatial navigation. Additionally, metabolic phenotyping, GMB sequencing throughout the intestinal tract (duodenum, jejunum, ileum, colon, and feces), neuropathological burden assessment and marker gene functional abundance predictions (PICRUSt2) were conducted. TgF344-AD rats demonstrated significant cognitive impairment in multiple domains, as well as regionally specific GMB dysbiosis. Relationships between peripheral factors were investigated using Canonical Correspondence Analysis (CCA), revealing correlations between GMB changes and both cognitive and metabolic factors. Moreover, communities of gut microbes contributing to essential metabolic pathways were significantly altered in TgF344-AD rats. These data indicate dysbiosis may affect cognitive outcomes in AD through alterations in metabolism-related enzymatic pathways that are necessary for proper brain function. Moreover, these changes were mostly observed in intestinal segments required for carbohydrate digestion, not fecal samples. These data support the targeting of intestinal and microbiome health for the treatment of AD.

Sensitivity of Mouse Lung Nuclear Receptors to Electronic Cigarette Aerosols and Influence of Sex Differences: A Pilot Study.

The emerging concern about chemicals in electronic cigarettes, even those without nicotine, demands the development of advanced criteria for their exposure and risk assessment. This study aims to highlight the sensitivity of lung nuclear receptors (NRs) to electronic cigarette e-liquids, independent of nicotine presence, and the influence of the sex variable on these effects. Adult male and female C57BL/6J mice were exposed to electronic cigarettes with 0%, 3%, and 6% nicotine daily (70 mL, 3.3 s, 1 puff per min/30 min) for 14 days, using the inExpose full body chamber (SCIREQ). Following exposure, lung tissues were harvested, and RNA extracted. The expression of 84 NRs was determined using the RT2 profiler mRNA array (Qiagen). Results exhibit a high sensitivity to e-liquid exposure irrespective of the presence of nicotine, with differential expression of NRs, including one (females) and twenty-four (males) in 0% nicotine groups compared to non-exposed control mice. However, nicotine-dependent results were also significant with seven NRs (females), fifty-three NRs (males) in 3% and twenty-three NRs (female) twenty-nine NRs (male) in 6% nicotine groups, compared to 0% nicotine mice. Sex-specific changes were significant, but sex-related differences were not observed. The study provides a strong rationale for further investigation.

Race/ethnic differences in the association of anxiety, depression, and discrimination with subsequent nicotine and cannabis use among young adults: A prospective longitudinal study.

INTRODUCTION: The shifting patterns in nicotine and cannabis use among young adults is taking place at a time when there is also increased reports of psychosocial stressors such as anxiety, depression, and everyday discrimination. Although race/ethnicity has been found to moderate the impact of psychosocial stressors, there is limited research examining the association of anxiety, depression, and discrimination with patterns of nicotine and/or cannabis product use among diverse young adults. METHODS: Data were from a longitudinal study of 2478 US young adults surveyed between 2019 and 2021. General estimating equation models were used to examine associations of self-reported psychological symptoms (depression, anxiety) and social stressors (discrimination) with substance use (any nicotine and cannabis product use; nicotine and cannabis vaping). RESULTS: Young adults from different racial/ethnic groups differed significantly in their depression and discrimination scores with young adults of color having higher mean scores. Overall, higher depression and everyday discrimination score was associated with increased odds of past 6-month use of any nicotine/tobacco and cannabis products. Higher generalized anxiety score increased odds of any nicotine/tobacco and dual nicotine and cannabis product use. Higher everyday discrimination score was associated with increased odds nicotine and cannabis vaping overall. Stratified models showed variation in associations among different racial/ethnic groups. CONCLUSIONS: Psychosocial stressors are associated with increased substance use odds among young adults. However, these stressors have a differential impact on substance use odds among young adults from different racial/ethnic contexts.

Impact of sustained calorie restriction and weight cycling on body composition in high-fat diet-fed male and female C57BL/6J mice.

OBJECTIVE: The objective of this study was to investigate body composition changes with weight cycling (WC) among adult C57BL/6J mice with diet-induced obesity. METHODS: A total of 555 single-housed mice were fed a high-fat diet ad libitum (AL) from 8 to 43 weeks of age. The 200 heaviest mice of each sex were randomized to the following four groups: ever obese (EO, continued AL feeding); obese weight loser (OWL, calorie-restricted); obese weight loser moderate (OWLM, body weight halfway between EO and OWL); and WC (diet restricted to OWL followed by AL refeeding cycles). Body weight and composition data were collected. Linear regression was used to calculate residuals between predicted and observed fat mass. Linear mixed models were used to compare diet groups. RESULTS: Although weight loss and regain resulted in changes in body weight and composition, fat mass, body weight, and relative body fat were not significantly greater for the WC group compared with the EO group. During long-term calorie restriction, males (but not females) in the OWLM group remained relatively fatter than the EO group. CONCLUSIONS: WC did not increase body weight or relative fat mass for middle-aged, high-fat diet-fed adult mice. However, long-term moderate calorie restriction resulted in lower body weight but greater "relative" fat in male mice.

Promoting Healthy Adolescent Romantic Relationships: Results of a Multisite, Two-group Parallel Randomized Clinical Trial.

PURPOSE: To examine the impact of About Us, an innovative healthy relationships intervention that promotes positive adolescent romantic relationships and the use of effective contraceptives, on improving behavior, attitudes, and intentions related to sexual intercourse, relationship communication, and conflict resolution at 3- and 9-month follow-up, compared to services as usual. METHODS: This was a multi-site, two-group, parallel, randomized-controlled trial with an intervention/comparison allocation ratio of 3:2 conducted at seven high schools in California between February 2018 and May 2021. RESULTS: Overall, our study did not find statistically significant evidence of improved behavior, attitudes, and intentions related to sexual intercourse, relationship communication, and conflict resolution among participants (14-18 years old) randomized to the intervention group (n = 316) compared to services as usual (n = 217) during follow-up (group x time; p > .05). Exploratory within group analyses showed that, compared to baseline, at the 3-month follow-up, the prevalence of reporting having had sex increased in the control group relative to intervention group (+19% vs. +9%, p < .01). Our sub-group analyses showed that changes in condom use intentions scores differed across school sites (group x time x school; p < .01); mixed (positive and negative) trends were observed for intervention effect, and schools with positive intervention effect trends tended to have greater program participation. DISCUSSION: About Us did not show statistically significant positive impacts on primary or secondary outcomes as anticipated. Our exploratory findings show evidence of some promising trends of intervention effects at the school-level, suggesting a need for better tailored intervention components and/or delivery to address the unique environmental contexts of participants. Overall, the context of study implementation was negatively affected by the COVID-19 pandemic and challenges related to using a non-classroom delivery intervention approach. Combined, these factors may have contributed to the study null findings. Moreover, it is difficult to know (or determine) the intervention's impact under more ideal conditions (i.e., no COVID pandemic).

Sex-specific alterations in the gut and lung microbiome of allergen-induced mice.

Introduction: Recent evidence has demonstrated that the microbiome is a driver of the underlying pathophysiological mechanisms of respiratory disease. Studies have indicated that bacterial metabolites produced in the gut and lung can impact lung inflammation and immune cell activity, affecting disease pathology. Despite asthma being a disease with marked sex differences, experimental work linking microbiomes and asthma has not considered the sex variable. Methods: To test the hypothesis that the lung and gut microbial composition impacts allergic lung inflammation in a sex-specific manner, we evaluated lung and gut microbiome alterations in a mouse model of allergic inflammation and assessed their association with lung function and inflammation phenotypes. For this, we exposed male and female adult C57BL/6J mice intranasally to 25 µg of a house dust mite extract mix (HDM) daily, or phosphate-buffered saline (PBS) as control, for 5 weeks (n = 4-6/group). DNA from fecal pellets collected before and after the 5-week treatment, and from lung tissue collected at endpoint, was extracted using the ZymoBIOMICS®-96 MagBead DNA Kit and analyzed to determine the 16S microbiome via Targeted Metagenomic Sequencing. Results: The HDM treatment induced a sex-specific allergic inflammation phenotype with significantly higher neutrophilia, lymphocytosis, inflammatory gene expression, and histopathological changes in females than males following exposure to HDM, but higher airway hyperresponsiveness (AHR) in males than females. In addition, sex-specific lung gene expression and associated pathways were identified HDM mix after challenge. These changes corresponded to sex-specific alterations in the gut microbiome, where the Firmicutes to Bacteroidetes ratio (F:B) was significantly reduced in fecal samples from only male mice after HDM challenge, and alpha diversity was increased in males, but decreased in females, after 5-weeks of HDM treatment. Discussion: Overall, our findings indicate that intranasal allergen challenge triggers sex-specific changes in both gut and lung microbiomes, and induces sex-specific lung inflammation, AHR, and lung inflammatory gene expression pathways, suggesting a contribution of the lung-gut axis in allergic airway disease.