Quantitative whole-tissue 3D imaging reveals bacteria in close association with mouse jejunum mucosa.

Because the small intestine (SI) epithelium lacks a thick protective mucus layer, microbes that colonize the thin SI mucosa may exert a substantial effect on the host. For example, bacterial colonization of the human SI may contribute to environmental enteropathy dysfunction (EED) in malnourished children. Thus far, potential bacterial colonization of the mucosal surface of the SI has only been documented in disease states, suggesting mucosal colonization is rare, likely requiring multiple perturbations. Furthermore, conclusive proof of bacterial colonization of the SI mucosal surface is challenging, and the three-dimensional (3D) spatial structure of mucosal colonies remains unknown. Here, we tested whether we could induce dense bacterial association with jejunum mucosa by subjecting mice to a combination of malnutrition and oral co-gavage with a bacterial cocktail (E. coli and Bacteroides spp.) known to induce EED. To visualize these events, we optimized our previously developed whole-tissue 3D imaging tools with third-generation hybridization chain reaction (HCR v3.0) probes. Only in mice that were malnourished and gavaged with the bacterial cocktail did we detect dense bacterial clusters surrounding intestinal villi suggestive of colonization. Furthermore, in these mice we detected villus loss, which may represent one possible consequence that bacterial colonization of the SI mucosa has on the host. Our results suggest that dense bacterial colonization of jejunum mucosa is possible in the presence of multiple perturbations and that whole-tissue 3D imaging tools can enable the study of these rare events.

Trends, heterogeneity, and correlates of mental health and psychosocial well-being in later-life: study of 590 community-dwelling adults aged 40-104 years.

OBJECTIVE: The goal of this study was to examine if mental health and psychosocial well-being differed between middle-aged (MA; 40-59 years), younger-old (YO; 60-79 years), and older-old (OO; 80+ years) adults with respect to their trends, heterogeneity, and correlates. METHODS: Eighteen mental health and psychosocial well-being instruments were administered to 590 adults over age 40. Cross-sectional data also included self-report-based measures of sociodemographics, cognitive functioning, physical health and activity, and body mass index. RESULTS: Age trends across instruments varied in magnitude and shape, but generally supported an inverted U-shaped trend in mental health and psychosocial well-being, with small increases from MA to YO age (d = 0.29) and smaller declines from YO to OO age (d = -0.17). A U-shaped association between age and mental health heterogeneity was also observed. The strongest correlates of mental health and psychosocial well-being differed by age (MA: perceived stress; YO: successful aging; OO: compassion toward others), as did the associations of a flourishing versus languishing mental health and well-being profile. CONCLUSIONS: Our findings support the "paradox of aging," whereby declines in physical and cognitive health co-occur with relatively preserved mental health and well-being. Our findings indicate that variance in mental and psychosocial health does not increase linearly with age and support careful consideration of heterogeneity in mental health and aging research. Our findings also suggest that mental health and psychosocial well-being decouple from stress-related dimensions in MA and become increasingly associated with positive, other-oriented emotions in OO, broadly supporting socioemotional theories of aging.

The Fecal Microbiome and Metabolome of Pitt Hopkins Syndrome, a Severe Autism Spectrum Disorder.

Alterations to the gut microbiome have been reported between children with autism spectrum disorders (ASDs) and typically developing (TD) children. Characterizing these differences has led to the proposal of new treatments for ASD, such as probiotic interventions and fecal matter transplants. However, no study to date has characterized the gut microbiome or metabolome in Pitt Hopkins syndrome (PTHS), a severe ASD with a high incidence of gastrointestinal (GI) disturbances such as constipation. Here, we surveyed the gut microbiome and metabolome in a cohort of PTHS individuals and their unaffected parents. We focused our analysis on Clostridium bolteae, a microbe previously associated with ASD known to chemically modify bile acids in the gut. PTHS individuals carry a higher load of C. bolteae than their parents as well as both ASD and non-ASD individuals from the American Gut Project cohort. Specific metabolites were associated with PTHS, including bile acids and sphingosines. With a metadata reanalysis tool, we found that PTHS-associated metabolites have previously been identified in inflammatory bowel disease and obesity patients. These results suggest microbial involvement in PTHS, but further research must be performed to clarify the exact mechanisms through which microbes may act. Furthermore, new associations between PTHS-specific metabolites and other conditions may lead to additional therapeutic options for PTHS individuals. IMPORTANCE GI disturbances in ASD such as severe constipation can be medically significant and often require medication. This is especially true for individuals with PTHS, suggesting that the gut microbiome may be involved in PTHS's pathology. Revealing associations between specific gut microbes and PTHS may allow the development of new therapeutics or the application of existing therapeutics to ease day-to-day challenges encountered by PTHS individuals. In this study, we characterized an association between C. bolteae and PTHS, in addition to metabolites linked to both PTHS and C. bolteae. We also identified other microbiome-involved medical conditions where PTHS-associated metabolites have been isolated. Utilizing common metabolites to identify conditions with similar phenotypes may suggest new therapeutic options for GI-related symptoms.