No abstract

Rationale: The elderly experience profound systemic responses after stroke, which contribute to higher mortality and more severe long-term disability. Recent studies have revealed that stroke outcomes can be influenced by the composition of gut microbiome. However, the potential benefits of manipulating the gut microbiome after injury is unknown. Objective: To determine if restoring youthful gut microbiota after stroke aids in recovery in aged subjects, we altered the gut microbiome through young fecal transplant gavage (young FTG) in aged mice after experimental stroke. Further, the effect of direct enrichment of selective bacteria producing short-chain fatty acids (SCFAs) was tested as a more targeted and refined microbiome therapy. Methods and Results: Aged male mice (18-20 months) were subjected to ischemic stroke by middle cerebral artery occlusion (MCAO). We performed FTG three days after MCAO using young donor biome (2-3 months) or aged biome (18-20 months). At day 14 after stroke, aged stroke mice receiving young FTG had less behavioral impairment, and reduced brain and gut inflammation. Based on data from microbial sequencing and metabolomics analysis demonstrating that young fecal transplants contained much higher SCFA levels and related bacterial strains, we selected four SCFA-producers (Bifidobacterium longum, Clostridium symbiosum, Faecalibacterium prausnitzii and Lactobacillus fermentum) for transplantation. These SCFA-producers alleviated post-stroke neurological deficits and inflammation, and elevated gut, brain and plasma SCFA concentrations in aged stroke mice. Conclusions: This is the first study suggesting that the poor stroke recovery in aged mice can be reversed via "post-stroke bacteriotherapy" following the replenishment of youthful gut microbiome via modulation of immunologic, microbial and metabolomic profiles in the host.

Background:This study investigated longitudinal patterns of psychological distress in adult survivors of childhood cancer.Methods:Participants included 4569 adult survivors in the Childhood Cancer Survivor Study Cohort (CCSS) who completed the Brief Symptom Inventory-18 on three occasions between 1994 and 2010. Longitudinal latent class analysis was used to identify discrete classes of psychological distress. Predictors of class membership were examined through logistic regression modelling with odds ratios (ORs) and 95% confidence intervals (CIs) reported.Results:Survivors were a median of 39 years of age and 30 years from diagnosis at the most recent follow-up. Most survivors reported few or no symptoms of distress over time, although subsets of survivors reported persistently elevated (depression: 8.9% anxiety: 4.8% somatisation: 7.2%) or significant increases in distress symptoms over the follow-up period (depression: 10.2% anxiety: 11.8% somatisation: 13.0%). Increasing distress symptoms were predicted by survivor perception of worsening physical health over time (depression: OR=3.3; 95% CI=2.4–4.5; anxiety: OR=3.0; 95% CI=2.2–4.0; somatisation: OR=5.3; 95% CI=3.9–7.4). Persistent distress symptoms were also predicted by survivor perception of worsening physical health over time, as well as by worsening pain and ending analgesic use.Conclusion:Subgroups of adult survivors are at-risk for chronic distress or significant increases in distress decades following their original cancer diagnosis. Routine screening of psychological distress in adult survivors of childhood cancer is warranted, especially for survivors who experience physical health morbidities.