A gut-brain-gut interoceptive circuit loop gates sugar ingestion in Drosophila.

The communication between the brain and digestive tract is critical for optimising nutrient preference and food intake, yet the underlying neural mechanisms remain poorly understood 1-7 . Here, we show that a gut-brain-gut circuit loop gates sugar ingestion in flies. We discovered that brain neurons regulating food ingestion, IN1 8 , receive excitatory input from enteric sensory neurons, which innervate the oesophagus and express the sugar receptor Gr43a. These enteric sensory neurons monitor the sugar content of food within the oesophagus during ingestion and send positive feedback signals to IN1s, stimulating the consumption of high-sugar foods. Connectome analyses reveal that IN1s form a core ingestion circuit. This interoceptive circuit receives synaptic input from enteric afferents and provides synaptic output to enteric motor neurons, which modulate the activity of muscles at the entry segments of the crop, a stomach-like food storage organ. While IN1s are persistently activated upon ingestion of sugar-rich foods, enteric motor neurons are continuously inhibited, causing the crop muscles to relax and enabling flies to consume large volumes of sugar. Our findings reveal a key interoceptive mechanism that underlies the rapid sensory monitoring and motor control of sugar ingestion within the digestive tract, optimising the diet of flies across varying metabolic states.

Blackcurrants shape gut microbiota profile and reduce risk of postmenopausal osteoporosis via the gut-bone axis: Evidence from a pilot randomized controlled trial.

This study aimed to investigate the effects of blackcurrant (BC) on gut microbiota abundance and composition, inflammatory and immune responses, and their relationship with bone mass changes. The effects of BC on bone mineral density (BMD), gut microbiota, and blood inflammatory and immune biomarkers were evaluated using DXA, stool and fasting blood collected from a pilot three-arm, randomized, double-blind, placebo-controlled clinical trial. Fifty-one peri- and early postmenopausal women aged 45-60 years were randomly assigned into one of three treatment groups for 6 months: control, low BC (392 mg/day) and high BC (784 mg/day); and 40 women completed the trial. BC supplementation for 6 months effectively mitigated the loss of whole-body BMD (P<.05). Six-month changes (%) in peripheral IL-1ß (P=.056) and RANKL (P=.052) for the high BC group were marginally significantly lower than the control group. Six-month changes in whole-body BMD were inversely correlated with changes in RANKL (P<.01). In proteome analysis, four plasma proteins showed increased expression in the high BC group: IGFBP4, tetranectin, fetuin-B, and vitamin K-dependent protein S. BC dose-dependently increased the relative abundance of Ruminococcus 2 (P<.05), one of six bacteria correlated with BMD changes in the high BC group (P<.05), suggesting it might be the key bacteria that drove bone protective effects. Daily BC consumption for 6 months mitigated bone loss in this population potentially through modulating the gut microbiota composition and suppressing osteoclastogenic cytokines. Larger-scale clinical trials on the potential benefits of BC and connection of Ruminococcus 2 with BMD maintenance in postmenopausal women are warranted. Trial Registration: NCT04431960, https://classic.clinicaltrials.gov/ct2/show/NCT04431960.

Blackcurrant Anthocyanins Improve Blood Lipids and Biomarkers of Inflammation and Oxidative Stress in Healthy Women in Menopause Transition without Changing Body Composition.

Recent cell and animal studies suggest the potential of blackcurrants (BCs; Ribes nigrum) as a dietary agent that may reduce the risk of cardiovascular disease (CVD) by improving dyslipidemia, oxidative stress, and inflammation. This study aimed to examine the effects of BC anthocyanin (ACN) extract supplementation on biomarkers of CVD risk in healthy adult women in menopause transition. The effects of BC ACN supplementation on body composition, fasting blood lipids and biomarkers of inflammation and oxidative stress were evaluated using anthropometric measures and blood samples collected from a pilot randomized controlled clinical trial in peri- and early postmenopausal women. Thirty-eight eligible peri- and early postmenopausal women aged 45-60 completed the entire trial, in which they were randomly assigned into one of three treatment groups: placebo (control group), 392 mg/day (low BC group), or 784 mg/day (high BC group) for six months. The significance of differences in outcomes was tested using repeated-measures ANOVA. Overall, following six-month BC consumption, significantly decreased triglyceride (TG) levels were observed between treatment groups (p < 0.05) in a dose-dependent manner. Plasma interleukin-1ß (IL-1ß) was significantly reduced in a dose and time dependent manner (p < 0.05). Significant decreases in thiobarbituric acid reactive substances (TBARS) levels were also observed between treatment groups (p < 0.05) in a dose-dependent manner. Six-month change in oxidized LDL was inversely correlated with changes in catalase (CAT) and total antioxidant capacity (TAC) (p < 0.05), while C-reactive protein (hs-CRP) change was positively correlated with changes in TG and IL-1ß (p < 0.01). Together, these findings suggest that daily BC consumption for six months effectively improved dyslipidemia, inflammation, and lipid peroxidation, thus potentially mitigating the risk of postmenopausal CVD development in study participants. Future studies with larger sample sizes and at-risk populations are warranted to confirm these findings.

Systematic analysis of YFP traps reveals common mRNA/protein discordance in neural tissues.

While post-transcriptional control is thought to be required at the periphery of neurons and glia, its extent is unclear. Here, we investigate systematically the spatial distribution and expression of mRNA at single molecule sensitivity and their corresponding proteins of 200 YFP trap lines across the intact Drosophila nervous system. 97.5% of the genes studied showed discordance between the distribution of mRNA and the proteins they encode in at least one region of the nervous system. These data suggest that post-transcriptional regulation is very common, helping to explain the complexity of the nervous system. We also discovered that 68.5% of these genes have transcripts present at the periphery of neurons, with 9.5% at the glial periphery. Peripheral transcripts include many potential new regulators of neurons, glia, and their interactions. Our approach is applicable to most genes and tissues and includes powerful novel data annotation and visualization tools for post-transcriptional regulation.

Blackcurrants Reduce the Risk of Postmenopausal Osteoporosis: A Pilot Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

Beneficial effects of blackcurrant supplementation on bone metabolism in mice has recently been demonstrated, but no studies are available in humans. The current study aimed to examine the dose-dependent effects of blackcurrant in preventing bone loss and the underlying mechanisms of action in adult women. Forty peri- and early postmenopausal women were randomly assigned into one of three treatment groups for 6 months: (1) a placebo (control group, n = 13); (2) 392 mg/day of blackcurrant powder (low blackcurrant, BC, group, n = 16); and (3) 784 mg/day of blackcurrant powder (high BC group, n = 11). The significance of differences in outcome variables was tested by repeated-measures ANOVA with treatment and time as between- and within-subject factors, respectively. Overall, blackcurrant supplementation decreased the loss of whole-body bone mineral density (BMD) compared to the control group (p < 0.05), though the improvement of whole-body BMD remained significant only in the high BC group (p < 0.05). Blackcurrant supplementation also led to a significant increase in serum amino-terminal propeptide of type 1 procollagen (P1NP), a marker of bone formation (p < 0.05). These findings suggest that daily consumption of 784 mg of blackcurrant powder for six months mitigates the risk of postmenopausal bone loss, potentially through enhancing bone formation. Further studies of larger samples with various skeletal conditions are warranted to confirm these findings.

Larval crowding accelerates C. elegans development and reduces lifespan.

Environmental conditions experienced during animal development are thought to have sustained impact on maturation and adult lifespan. Here we show that in the model organism C. elegans developmental rate and adult lifespan depend on larval population density, and that this effect is mediated by excreted small molecules. By using the time point of first egg laying as a marker for full maturity, we found that wildtype hermaphrodites raised under high density conditions developed significantly faster than animals raised in isolation. Population density-dependent acceleration of development (Pdda) was dramatically enhanced in fatty acid ß-oxidation mutants that are defective in the biosynthesis of ascarosides, small-molecule signals that induce developmental diapause. In contrast, Pdda is abolished by synthetic ascarosides and steroidal ligands of the nuclear hormone receptor DAF-12. We show that neither ascarosides nor any known steroid hormones are required for Pdda and that another chemical signal mediates this phenotype, in part via the nuclear hormone receptor NHR-8. Our results demonstrate that C. elegans development is regulated by a push-pull mechanism, based on two antagonistic chemical signals: chemosensation of ascarosides slows down development, whereas population-density dependent accumulation of a different chemical signal accelerates development. We further show that the effects of high larval population density persist through adulthood, as C. elegans larvae raised at high densities exhibit significantly reduced adult lifespan and respond differently to exogenous chemical signals compared to larvae raised at low densities, independent of density during adulthood. Our results demonstrate how inter-organismal signaling during development regulates reproductive maturation and longevity.