Background “Western” style dietary patterns are characterized by a high proportion of highly processed foods rich in fat and low in fiber. This diet pattern is associated with a myriad of metabolic dysfunctions, including neuroinflammation and cognitive impairment. β-glucan, the major soluble fiber in oat and barley grains, is fermented in the lower gastrointestinal tract, potentially impacting the microbial ecosystem and thus may improve elements of cognition and brain function via the gut-brain axis. The present study aimed to evaluate the effect of β-glucan on the microbiota gut-brain axis and cognitive function in an obese mouse model induced by a high-fat and fiber-deficient diet (HFFD). Results After long-term supplementation for 15 weeks, β-glucan prevented HFFD-induced cognitive impairment assessed behaviorally by object location, novel object recognition, and nesting building tests. In the hippocampus, β-glucan countered the HFFD-induced microglia activation and its engulfment of synaptic puncta, and upregulation of proinflammatory cytokine (TNF-α, IL-1β, and IL-6) mRNA expression. Also, in the hippocampus, β-glucan significantly promoted PTP1B-IRS-pAKT-pGSK3β-pTau signaling for synaptogenesis, improved the synaptic ultrastructure examined by transmission electron microscopy, and increased both pre- and postsynaptic protein levels compared to the HFFD-treated group. In the colon, β-glucan reversed HFFD-induced gut barrier dysfunction increased the thickness of colonic mucus (Alcian blue and mucin-2 glycoprotein immunofluorescence staining), increased the levels of tight junction proteins occludin and zonula occludens-1, and attenuated bacterial endotoxin translocation. The HFFD resulted in microbiota alteration, effects abrogated by long-term β-glucan supplementation, with the β-glucan effects on Bacteroidetes and its lower taxa particularly striking. Importantly, the study of short-term β-glucan supplementation for 7 days demonstrated pronounced, rapid differentiating microbiota changes before the cognitive improvement, suggesting the possible causality of gut microbiota profile on cognition. In support, broad-spectrum antibiotic intervention abrogated β-glucan’s effects on improving cognition, highlighting the role of gut microbiota to mediate cognitive behavior. Conclusion This study provides the first evidence that β-glucan improves indices of cognition and brain function with major beneficial effects all along the gut microbiota-brain axis. Our data suggest that elevating consumption of β-glucan-rich foods is an easily implementable nutritional strategy to alleviate detrimental features of gut-brain dysregulation and prevent neurodegenerative diseases associated with Westernized dietary patterns.

Background Cognitive impairment, an increasing mental health issue, is a core feature of the aging brain and neurodegenerative diseases. Industrialized nations especially, have experienced a marked decrease in dietary fiber intake, but the potential mechanism linking low fiber intake and cognitive impairment is poorly understood. Emerging research reported that the diversity of gut microbiota in Western populations is significantly reduced. However, it is unknown whether a fiber-deficient diet (which alters gut microbiota) could impair cognition and brain functional elements through the gut-brain axis. Results In this study, a mouse model of long-term (15 weeks) dietary fiber deficiency (FD) was used to mimic a sustained low fiber intake in humans. We found that FD mice showed impaired cognition, including deficits in object location memory, temporal order memory, and the ability to perform daily living activities. The hippocampal synaptic ultrastructure was damaged in FD mice, characterized by widened synaptic clefts and thinned postsynaptic densities. A hippocampal proteomic analysis further identified a deficit of CaMKIId and its associated synaptic proteins (including GAP43 and SV2C) in the FD mice, along with neuroinflammation and microglial engulfment of synapses. The FD mice also exhibited gut microbiota dysbiosis (decreased Bacteroidetes and increased Proteobacteria), which was significantly associated with the cognitive deficits. Of note, a rapid differentiating microbiota change was observed in the mice with a short-term FD diet (7 days) before cognitive impairment, highlighting a possible causal impact of the gut microbiota profile on cognitive outcomes. Moreover, the FD diet compromised the intestinal barrier and reduced short-chain fatty acid (SCFA) production. We exploit these findings for SCFA receptor knockout mice and oral SCFA supplementation that verified SCFA playing a critical role linking the altered gut microbiota and cognitive impairment. Conclusions This study, for the first time, reports that a fiber-deprived diet leads to cognitive impairment through altering the gut microbiota-hippocampal axis, which is pathologically distinct from normal brain aging. These findings alert the adverse impact of dietary fiber deficiency on brain function, and highlight an increase in fiber intake as a nutritional strategy to reduce the risk of developing diet-associated cognitive decline and neurodegenerative diseases.

AimTo report our experience regarding management of cholecystoenteric fistula (CEF) and identify the most effective diagnostic methods and surgical treatment.MethodsIn total, 10,588 patients underwent laparoscopic cholecystectomy for cholecystolithiasis from January 2000 to December 2014 at the Research Institute of General Surgery, Jinling Hospital (Nanjing, China). Twenty-nine patients were diagnosed with CEF preoperatively or intraoperatively. Data were retrospectively collected on demographics, preoperative diagnostics, intraoperative findings, laparoscopic procedures, complications, and follow-up.ResultsTwenty-nine patients (female/male ratio, 2.2; mean age, 68.7 years) with CEF were evaluated. Twenty-three (79.3%) patients had a cholecystoduodenal fistula (CDF), four (13.8%) had a cholecystocolonic fistula (CCF), one (3.4%) had a cholecystogastric fistula, and one (3.4%) had a CDF combined with a CCF. Only nine (31.0%) patients obtained a preoperative diagnosis. All patients initially underwent laparoscopic treatment, but five (17.2%) underwent conversion to open surgery; three of these five developed postoperative morbidity or mortality, and the other two had an uneventful postoperative course. Among patients managed successfully by laparoscopy, the hospital stay ranged from 3 to 6 days (mean, 4 days). All patients were asymptomatic at a mean follow-up of 13 months (range, 3–21 months).ConclusionUltrasound and computed tomography can provide valuable diagnostic clues for CEF. Laparoscopic management of CEF in experienced hands is safe, feasible, and associated with rapid postoperative recovery.

Background: “Western” style dietary patterns are characterised by a high proportion of highly processed foods rich in fat and low in fibre. This diet-pattern is associated with myriad metabolic dysfunctions including neuroinflammation and cognitive impairment. β-glucan, the major soluble fibre in oat and barley grains, are fermented in the lower gastrointestinal tract, potentially impacting the microbial ecosystem and thus may improve elements of the gut-brain axis. The present study aimed to evaluate the effect of β-glucan on the microbiota-gut-brain axis and cognitive function in an obese mouse model induced by a high-fat and fibre deficient diet (HFFD). Results: After chronic supplementation for 15 weeks, β-glucan prevented HFFD diet-induced cognitive impairment assessed behaviourally by object location and nesting building tests. In the hippocampus, β-glucan countered the HFFD-induced microglia activation and its engulfment of synaptic puncta, and up-regulation of proinflammatory cytokine (TNF-α, IL-1β and IL-6) mRNA expression. Also in the hippocampus, β-glucan significantly promoted PTP1B-IRS-pAKT-pGSK3β-pTau signalling for synaptogenesis; improved the synaptic ultrastructure examined by transmission electron microscopy and increased both pre- and post-synaptic protein levels compared to the HFFD-treated group. In the colon, β-glucan reversed HFFD-induced gut barrier dysfunction: increased the thickness of colonic mucus (Alcian blue and mucin-2 glycoprotein immunofluorescence staining); increased the levels of tight junction proteins occludin and zonula occludens-1; and attenuated bacterial endotoxin translocation. The HFFD diet resulted in widespread microbiota dysbiosis, effects abrogated by chronic β-glucan supplementation, with the β-glucan effects on bacteroidetes and its lower taxa particularly striking. Importantly, acute study of β-glucan supplementation for 7 days demonstrated pronounced, rapid differentiating microbiota changes before the cognitive improvement, suggesting the possible causality of gut microbiota profile on cognition. In support, broad-spectrum antibiotic intervention to severely deplete gut microbiota colonisation, eliminated β-glucan’s effects on improving cognition, highlighting the role of gut microbiota to mediate cognitive behavior. Conclusion: This study provides the first evidence that β-glucan improves indices of cognition and brain function with major beneficial effects all along the gut microbiota-brain axis. Our data suggest that elevating consumption of β-glucan-rich foods is an easily implementable nutritional strategy to alleviate detrimental features of gut-brain dysregulation and prevent neurodegenerative diseases associated with Westernized dietary patterns.

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Cannabidiol (CBD), a phytocannabinoid from the Cannabis sativa plant, exhibits a broad spectrum of potential therapeutic properties for neurodegenerative diseases.An accumulation of amyloid-β (Aβ) protein is one of the most important neuropathology in neurodegenerative diseases like Alzheimer's disease (AD). Data on the effect of CBD on the amelioration of Aβ-induced neurite degeneration and its consequences of life and health spans is sparse. This study aimed to investigate the effects of CBD on neurite outgrowth in cells and lifespan and health span in Caenorhabditis elegans (C. elegans). In human SH-SY5Y neuronal cells, CBD prevented neurite lesion induced by Aβ 1-42 and increased the expression of fatty acid amide hydrolase (FAAH) and cannabinoid receptor 1 (CB1R). Furthermore, CBD both protected the reduction of dendritic spine density and rescued the activity of synaptic Ca 2+ / calmodulin-dependent protein kinase II (CaMKII) from Aβ 1-42 toxicity in primary hippocampal neurons. In C. elegans, we used the transgenic CL2355 strain of C. elegans, which expresses the human Aβ peptide throughout the nervous system and found that CBD treatment extended lifespan and improved health span. The neuroprotective effect of CBD was further explored by observing the dopaminergic neurons using transgenic dat-1: GFP strains using the confocal microscope. This study shows that CBD prevents the neurite degeneration induced by Aβ, by a mechanism involving CB1R activation, and extends lifespan and improves health span in Aβoverexpressing worms. Our findings support the potential therapeutic approach of CBD for the treatment of AD patients.