Draft genome sequence of Bacillus atrophaeus TL401, a biocontrol bacterium with plant growth-promoting properties.

Bacillus atrophaeus strain TL401 exhibits biocontrol activity against Botrytis cinerea on tomato and plant growth promotion. Here, we present the draft genome sequence of strain ITL401, which includes a circular chromosome with 4,213,034 bp and a guanine-cytosine content of 43.39%.

Three-dimensional Reconstruction and Comparison of Temporomandibular Joint Space Volume Before and After Orthognathic Surgery in Patients with Skeletal Class III Malocclusion With Mandibular Deviation.

OBJECTIVE: To look into the association between the degree of deviation and the changing trend in the temporomandibular joint (TMJ) space volume after orthognathic surgery in patients with skeletal Class III malocclusion. METHODS: Twenty patients having combined orthodontic-orthognathic treatment for skeletal Class III malocclusions with mandibular deviation were chosen, and craniofacial spiral CT was performed before (T0), two weeks after (T1), and six months after (T2) surgery. Using 3D volume reconstruction, further partitioning, and analysis of each domain's volume changes over time, the TMJ space volume is to be obtained. The differences in changes between groups A (mild deviation group) and B (severe deviation group) were examined to examine the impact of the degree of deviation on the TMJ space volume. RESULTS: A statistically significant difference ( P <0.05) existed between the postoperative TMJ space volume in group A and the preoperative overall, anterolateral, and anteroinferior space volume; the same difference also existed between the postoperative TMJ space volume in the NDS and the preoperative posterolateral, posteroinferior space volume. In group B, the postoperative TMJ space volume was statistically significant ( P <0.05) compared with the preoperative total and anteroinferior space volume in the DS; the difference between the total volume of the T1 stage on the NDS and the total volume of the T0 stage was statistically significant ( P <0.05). The two groups showed substantial differences in the space volume changes between the T1-T0 phase and the T2-T1 period. CONCLUSION: Patients with skeletal Class III malocclusion and mandibular deviation after orthognathic surgery see a change in the TMJ space volume. All patient types experience a largely consistent space volume change trend two weeks after surgery, and the degree of mandibular deviation is correlated with the intensity and longevity of the alteration.

Advances in the natural history of urinary incontinence in adult females.

The aim of this review is to summarise the related characteristics of the natural history of female urinary incontinence (UI) using a narrative descriptive approach. PubMed, EMBASE and Web of Science were searched for articles published from 1 January 2010 to 1 January 2020 on the natural history of female UI, which including incidence, persistence, progression, remission, and regression of a single subtype of UI and the mutual influence of different UI subtypes. This literature review includes 15 articles published, indicates that UI is highly dynamic, with symptoms varying according to disease severity and subtype and influenced by multiple factors at different disease stages. Recent studies have increased our understanding of the natural history of UI. Future research should systematically analyse the progression of each subtype of UI and interactions between subtypes to prevent the progression of UI across females life course.

Dimethyl itaconate ameliorates cognitive impairment induced by a high-fat diet via the gut-brain axis in mice.

BACKGROUND: Gut homeostasis, including intestinal immunity and microbiome, is essential for cognitive function via the gut-brain axis. This axis is altered in high-fat diet (HFD)-induced cognitive impairment and is closely associated with neurodegenerative diseases. Dimethyl itaconate (DI) is an itaconate derivative and has recently attracted extensive interest due to its anti-inflammatory effect. This study investigated whether intraperitoneal administration of DI improves the gut-brain axis and prevents cognitive deficits in HF diet-fed mice. RESULTS: DI effectively attenuated HFD-induced cognitive decline in behavioral tests of object location, novel object recognition, and nesting building, concurrent with the improvement of hippocampal RNA transcription profiles of genes associated with cognition and synaptic plasticity. In agreement, DI reduced the damage of synaptic ultrastructure and deficit of proteins (BDNF, SYN, and PSD95), the microglial activation, and neuroinflammation in the HFD-fed mice. In the colon, DI significantly lowered macrophage infiltration and the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) in mice on the HF diet, while upregulating the expression of immune homeostasis-related cytokines (IL-22, IL-23) and antimicrobial peptide Reg3γ. Moreover, DI alleviated HFD-induced gut barrier impairments, including elevation of colonic mucus thickness and expression of tight junction proteins (zonula occludens-1, occludin). Notably, HFD-induced microbiome alteration was improved by DI supplementation, characterized by the increase of propionate- and butyrate-producing bacteria. Correspondingly, DI increased the levels of propionate and butyrate in the serum of HFD mice. Intriguingly, fecal microbiome transplantation from DI-treated HF mice facilitated cognitive variables compared with HF mice, including higher cognitive indexes in behavior tests and optimization of hippocampal synaptic ultrastructure. These results highlight the gut microbiota is necessary for the effects of DI in improving cognitive impairment. CONCLUSIONS: The present study provides the first evidence that DI improves cognition and brain function with significant beneficial effects via the gut-brain axis, suggesting that DI may serve as a novel drug for treating obesity-associated neurodegenerative diseases. Video Abstract.

Association between Serum Oxytocin, Bone Mineral Density and Body Composition in Chinese Adult Females.

Background and Objectives: Oxytocin (OT) is a neuropeptide hormone which is known for its classical effects in pregnancy and lactation. Recently, growing evidence demonstrated a close relation between OT and bone. The present study aimed to explore the relationship between OT, bone and osteoporosis risk in Chinese adult females. Materials and Methods: in total, 149 adult females were enrolled. The serum OT levels were measured using ELISA kits. Bone mineral density (BMD) and body composition were measured by dual-energy X-ray absorptiometry (DXA). The study subjects were divided into two groups according to their menopause status and then divided into tertiles based on their serum OT level. Results: Serum OT, serum estradiol and BMD at three skeletal sites were significantly higher in the premenopausal group than in the postmenopausal group (p < 0.001, p = 0.008 and p < 0.001, respectively). In the tertile analysis, relative to tertile 1, significant associations were found for tertile 3 for OT levels and higher BMD in the femoral neck and total hip, in both pre- and postmenopausal groups. Using logistic regression analysis, tertile 3 appeared less likely to have low-BMD osteoporosis than tertile 1 (OR = 0.257, 95% CI = 0.073, 0.910). In multivariate stepwise regression analysis, OT and total lean mass were two positive determinants of BMD in the femoral neck and total hip in the premenopausal group (adjusted R2 for the model = 0.232 and 0.199, respectively; both p < 0.001). Conclusion: Our study demonstrated positive associations between serum OT levels and BMD in a Chinese (non-Caucasian) population. OT appeared to be more strongly associated with hip BMD in premenopausal females. These results may suggest a protective role and potential therapeutic use of OT in osteoporosis, especially for premenopausal women.

MicroRNAs in Serum Exosomes as Circulating Biomarkers for Postmenopausal Osteoporosis.

Postmenopausal osteoporosis (PMOP) is the most common skeletal disease in postmenopausal women and has become a global public health issue. Emerging evidence demonstrated the important relationship between microRNAs and PMOP. However, miRNAs have not yet been reported in PMOP. Hence, the present study aimed to investigate the differences in miRNA expression profiles in PMOP with fragility fractures to identify the key circulating miRNAs in serum exosomes and to validate these molecules as potential biomarkers. Postmenopausal women with osteoporotic fracture and normal bone mass were enrolled. Serum exosomes were isolated by traditional differential ultracentrifugation from participants. Isolated exosomes were identified by electron microscopy, western blotting and nanoparticle-tracking analysis and then examined for exosomal small RNA sequencing. The expression of miRNAs was compared by sRNA deep sequencing and bioinformatics analysis. Three miRNAs (mir-324-3p, mir-766-3p and mir-1247-5p) were found to be associated with BMD of L1-L4, FN (femur neck) and TH (total hip), while mir-330-5p and mir-3124-5p were associated with BMD of FN and TH. Furthermore, mir-330-5p was found to promote the ALP activity of hBMSCs, while mir-3124-5p showed the opposite result. The results showed that serum exosomal miRNAs were differentially expressed in postmenopausal osteoporosis patients with fragility fractures. Our study provides the first evidence that exosomal miRNA profiling revealed aberrant circulating miRNA in postmenopausal osteoporosis. Mir-324-3p, mir-766-3p, mir-1247-5p, mir-330-5p and mir-3124-5p, which were associated with bone mineral density (BMD), may serve as candidate diagnostic biomarkers as well as potentially contribute to pathophysiology of PMOP.

Identification of VdASP F2-interacting protein as a regulator of microsclerotial formation in Verticillium dahliae.

Verticillium dahliae, a notorious phytopathogenic fungus, causes vascular wilt diseases in many plant species. The melanized microsclerotia enable V. dahliae to survive for years in soil and are crucial for its disease cycle. In a previous study, we characterized the secretory protein VdASP F2 from V. dahliae and found that VdASP F2 deletion significantly affected the formation of microsclerotia under adverse environmental conditions. In this study, we clarified that VdASP F2 is localized to the cell wall. However, the underlying mechanism of VdASP F2 in microsclerotial formation remains unclear. Transmembrane ion channel protein VdTRP was identified as a candidate protein that interacts with VdASP F2 using pull-down assays followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and interaction of VdASP F2 and VdTRP was confirmed by bimolecular fluorescence complementary and coimmunoprecipitation assays. The deletion mutant was analysed to reveal that VdTRP is required for microsclerotial production, but it is not essential for stress resistance, carbon utilization and pathogenicity of V. dahliae. RNA-seq revealed some differentially expressed genes related to melanin synthesis and microsclerotial formation were significantly downregulated in the VdTRP deletion mutants. Taken together, these results indicate that VdASP F2 regulates the formation of melanized microsclerotia by interacting with VdTRP.

A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites.

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. Video Abstract.

Serum concentrations of oxytocin, DHEA and follistatin are associated with osteoporosis or sarcopenia in community-dwelling postmenopausal women.

BACKGROUND: Osteoporosis and sarcopenia are major health issues in postmenopausal women due to their high prevalence and association with several adverse outcomes. However, no biomarkers may be used for screening and diagnosis. The current study investigated potential biomarkers for osteoporosis and/or sarcopenia in postmenopausal women. METHODS: A cross-sectional study on 478 healthy community-dwelling postmenopausal women aged 50-90 years was performed. Osteoporosis and sarcopenia were defined according to the World Health Organization (WHO) and Asian Working Group for Sarcopenia (AWGS). RESULTS: Dehydroepiandrosterone (DHEA) was related to muscle strength (ß = 0.19, p = 0.041) and function (ß = 0.58, p = 0.004). Follistatin (ß = - 0.27, p = 0.01) was related to muscle mass. Oxytocin (ß = 0.59, p = 0.044) and DHEA (ß = 0.51, p = 0.017) were related to bone mass. After adjusting for age, oxytocin (odds ratio (OR) 0.75; 95% confidence intervals (CI) 0.63-0.98; p = 0.019) was associated with osteoporosis, and DHEA (OR 0.73; 95% CI 0.51-0.96; p = 0.032) and follistatin (OR 1.66; 95% CI 1.19-3.57; p = 0.022) were associated with sarcopenia. CONCLUSIONS: Postmenopausal women with sarcopenia were more likely to have lower DHEA levels and higher follistatin levels, and postmenopausal women with osteoporosis were more likely to have lower oxytocin levels.

Dicyanamide Anion-Based Ionic Liquid-Functionalized Graphene-Supported Pt Catalysts for Boosting Methanol Electrooxidation.

As an environmentally friendly energy technology, direct methanol fuel cells (DMFCs) meet the needs of sustainable development. Herein, novel dicyanamide anion-based (N(CN)2-) ionic liquid (IL)-functionalized reduced graphene oxide (rGO)-supported Pt catalysts are synthesized via a facile one-pot room temperature reduction method, which show a boost in methanol oxidation performance compared with Pt/rGO. The mass activities of the as-prepared Pt/emimN(CN)2/rGO (863.6 mA mg-1Pt) and Pt/epyN(CN)2/rGO (524.9 mA mg-1Pt) are about five and three times higher than that of Pt/rGO (178.6 mA mg-1Pt), and about six and four times higher than that of Pt/C (140.2 mA mg-1Pt), respectively. The participation of ILs significantly improves the CO poisoning resistance, stability, and activity for methanol oxidation of catalysts. The relationship between the structures and conductivities of diverse ILs and the performance of Pt catalysts are studied systematically. These findings may offer a promising prospect of ILs in DMFCs.

ZEB1 Mediates Bone Marrow Mesenchymal Stem Cell Osteogenic Differentiation Partly via Wnt/ß-Catenin Signaling.

Zinc finger E-box-binding homebox 1 (ZEB1) is a zinc-finger transcription factor best known for its role in promoting the epithelial-mesenchymal transition, which is also related to osteogenesis. Here, ZEB1 was investigated for its role in the commitment of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts. In vitro, ZEB1 expression decreased following osteogenic differentiation. Furthermore, silencing of ZEB1 in BMSCs promoted osteogenic activity and mineralization. The increase in osteogenic differentiation induced by si-ZEB1 could be partly rescued by the inhibition of Wnt/ß-catenin (si-ß-catenin). In vivo, knockdown of ZEB1 in BMSCs inhibited the rapid bone loss of ovariectomized (OVX) mice. ZEB1 expression has also been negatively associated with bone mass and bone formation in postmenopausal women. In conclusion, ZEB1 is an essential transcription factor in BMSC differentiation and may serve as a potential anabolic strategy for treating and preventing postmenopausal osteoporosis (PMOP).

ß-Glucan from Lentinula edodes prevents cognitive impairments in high-fat diet-induced obese mice: involvement of colon-brain axis.

BACKGROUND: Long-term high fat (HF) diet intake can cause neuroinflammation and cognitive decline through the gut-brain axis. (1, 3)/(1, 6)-ß-glucan, an edible polysaccharide isolated from medical mushroom, Lentinula edodes (L. edodes), has the potential to remodel gut microbiota. However, the effects of L. edodes derived ß-glucan against HF diet-induced neuroinflammation and cognitive decline remain unknown. This study aimed to evaluate the neuroprotective effect and mechanism of dietary L edodes ß-glucan supplementation against the obesity-associated cognitive decline in mice fed by a HF diet. METHODS: C57BL/6J male mice were fed with either a lab chow (LC), HF or HF with L. edodes ß-glucan supplementation diets for 7 days (short-term) or 15 weeks (long-term). Cognitive behavior was examined; blood, cecum content, colon and brain were collected to evaluate metabolic parameters, endotoxin, gut microbiota, colon, and brain pathology. RESULTS: We reported that short-term and long-term L. edodes ß-glucan supplementation prevented the gut microbial composition shift induced by the HF diet. Long-term L. edodes ß-glucan supplementation prevented the HF diet-induced recognition memory impairment assessed by behavioral tests (the temporal order memory, novel object recognition and Y-maze tests). In the prefrontal cortex and hippocampus, the ß-glucan supplementation ameliorated the alteration of synaptic ultrastructure, neuroinflammation and brain-derived neurotrophic factor (BDNF) deficits induced by HF diet. Furthermore, the ß-glucan supplementation increased the mucosal thickness, upregulated the expression of tight junction protein occludin, decreased the plasma LPS level, and inhibited the proinflammatory macrophage accumulation in the colon of mice fed by HF diet. CONCLUSIONS: This study revealed that L. edodes ß-glucan prevents cognitive impairments induced by the HF diet, which may occur via colon-brain axis improvement. The finding suggested that dietary L. edodes ß-glucan supplementation may be an effective nutritional strategy to prevent obesity-associated cognitive decline.

Self-Reported Depressive Symptoms Might be Associated with Sudomotor Dysfunction in Chinese T2DM Patients.

AIMS: To determine the relationships of sudomotor functions, nerve conductions and self-reported depressive symptoms in Chinese type 2 diabetes (T2DM) patients. METHODS: T2DM patients in a single community health center were included in this study. Demographic, medical and laboratory data were collected. Michigan Neuropathy Screening Instrument (MNSI) examination was conducted in all patients. SUDOSCAN test and Point-of-care Nerve Conduction Device (DPN-check) were conducted and all the patients finished the Patient Health Questionnaire-9 (PHQ-9). RESULTS: A total of 162 T2DM patients (74 males and 88 females) were included. The mean age was 69.0±7.2 years and the mean course of diabetes was 10.5±8.0 years with a mean HbA1c level of 7.3±1.4%. Thirty of them (18.5%) had self-reported depressive symptoms (PHQ-9 scores≥5). Diabetic peripheral neuropathy (DPN) was diagnosed according to the MSNI examination in 74 patients. Electrochemical skin conductance (ESC) values of both hands and feet were significantly lower in patients with depressive symptoms (Hands ESC: 60.63±18.92 vs. 67.64±16.02 µS, p<0.05; Feet ESC: 59.60 ± 15.19 vs. 66.19±14.99 µS, p<0.05). The proportion of patients with moderate to severe depressive symptoms were significantly higher in those with ESC values<60 µS (13.33% vs. 3.846%, p<0.05). Hands ESC values were negatively related to PHQ-9 scores (r =- 0.168, p<0.05). After adjusting for variables, hands and feet ESC values remained negatively related with depressive symptoms (ß =- 0.036 and-0.038, p<0.05). Female were positively related to depressive symptoms with odds ratio 3.4 (95%CI 1.1-10.5, p<0.05). CONCLUSION: Self-reported depressive symptoms might be associated with sudomotor dysfunction in Chinese T2DM patients.

ß-glucan attenuates cognitive impairment via the gut-brain axis in diet-induced obese mice.

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. ß-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 ß-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, ß-glucan prevented HFFD-induced cognitive impairment assessed behaviorally by object location, novel object recognition, and nesting building tests. In the hippocampus, ß-glucan countered the HFFD-induced microglia activation and its engulfment of synaptic puncta, and upregulation of proinflammatory cytokine (TNF-α, IL-1ß, and IL-6) mRNA expression. Also, in the hippocampus, ß-glucan significantly promoted PTP1B-IRS-pAKT-pGSK3ß-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, ß-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 ß-glucan supplementation, with the ß-glucan effects on Bacteroidetes and its lower taxa particularly striking. Importantly, the study of short-term ß-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 ß-glucan's effects on improving cognition, highlighting the role of gut microbiota to mediate cognitive behavior. CONCLUSION: This study provides the first evidence that ß-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 ß-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. Video Abstract.

Rapid and colorimetric detection of nucleic acids based on entropy-driven circuit and DNAzyme-mediated autocatalytic reactions.

In this work, a novel, rapid and enzyme-free colorimetric biosensor for the detection of nucleic acids has been developed based on entropy-driven (EDC) circuit and DNAzyme-mediated autocatalytic reactions. On sensing the target DNA, the EDC reaction could be initiated and the intact Mg2+-dependent DNAzyme was formed in the reaction product; then, a "mimic target" DNA was generated during the cleavage process of DNAzyme, which in turn catalyzed the EDC reaction corresponding to an autocatalytic process. Meanwhile, numerous G-quadruplex structures were released and further interacted with hemin to form peroxidase-mimicking DNAzyme, inducing a remarkably amplified colorimetric signal. This autocatalytic EDC (AEDC) sensing system exhibited a linear relationship in the range from 20 pM to 10 nM with a detection limit of 10.2 pM. More importantly, benefitting from the Mg2+-dependent DNAzyme-mediated autocatalytic reaction, the detection time (20 min) was significantly reduced compared to that for the reported EDC strategies. In addition, this sensing system has been applied for the detection of target DNA in human serum samples, indicating that it is promising for the on-site and real-time detection of nucleic acids in biomedical research and disease diagnosis.

DHA reduces hypothalamic inflammation and improves central leptin signaling in mice.

AIMS: Anti-obesity effects and improved leptin sensitivity from n-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported in diet-induced obese animals. This study sought to determine the beneficial central effects and mechanism of docosahexaenoic acid (DHA, 22:6 n-3) in high-fat (HF) diet fed mice. MAIN METHODS: Male C57BL/6J mice were given HF diet with or without intracerebroventricular (icv) injection of docosahexaenoic acid (DHA, 22:6 n-3) for two days. Central leptin sensitivity, hypothalamic inflammation, leptin signaling molecules and tyrosine hydroxylase (TH) were examined by central leptin sensitivity test and Western blot. Furthermore, the expression of hepatic genes involved in lipid metabolism was examined by RT-PCR. KEY FINDINGS: We found that icv administration of DHA not only reduced energy intake and body weight gain but also corrected the HF diet-induced hypothalamic inflammation. DHA decreased leptin signaling inhibitor SOCS3 and improved the leptin JAK2-Akt signaling pathways in the hypothalamus. Furthermore, icv administration of DHA improved the effects of leptin in the regulation of mRNA expression of enzymes related to lipogenesis, fatty acid ß-oxidation, and cholesterol synthesis in the liver. DHA increased leptin-induced activation of TH in the hypothalamus. SIGNIFICANCE: Therefore, increasing central DHA concentration may prevent the deficit of hypothalamic regulation, which is associated with disorders of energy homeostasis in the liver as a result of a high-fat diet.

Curdlan Prevents the Cognitive Deficits Induced by a High-Fat Diet in Mice via the Gut-Brain Axis.

A high-fat (HF) diet is a major predisposing factor of neuroinflammation and cognitive deficits. Recently, changes in the gut microbiota have been associated with neuroinflammation and cognitive impairment, through the gut-brain axis. Curdlan, a bacterial polysaccharide widely used as food additive, has the potential to alter the composition of the microbiota and improve the gut-brain axis. However, the effects of curdlan against HF diet-induced neuroinflammation and cognitive decline have not been investigated. We aimed to evaluate the neuroprotective effect and mechanism of dietary curdlan supplementation against the obesity-associated cognitive decline observed in mice fed a HF diet. C57Bl/6J male mice were fed with either a control, HF, or HF with curdlan supplementation diets for 7 days (acute) or 15 weeks (chronic). We found that acute curdlan supplementation prevented the gut microbial composition shift induced by HF diet. Chronic curdlan supplementation prevented cognitive declines induced by HF diet. In addition, curdlan protected against the HF diet-induced abnormities in colonic permeability, hyperendotoxemia, and colonic inflammation. Furthermore, in the prefrontal cortex (PFC) and hippocampus, curdlan mitigated microgliosis, neuroinflammation, and synaptic impairments induced by a HF diet. Thus, curdlan-as a food additive and prebiotic-can prevent cognitive deficits induced by HF diet via the colon-brain axis.

Supplement of microbiota-accessible carbohydrates prevents neuroinflammation and cognitive decline by improving the gut microbiota-brain axis in diet-induced obese mice.

BACKGROUND: Western pattern diets induce neuroinflammation and impair cognitive behavior in humans and animals. Neuroinflammation and cognitive impairment have been associated with microbiota dysbiosis, through the gut-brain axis. Furthermore, microbiota-accessible carbohydrates (MACs) found in dietary fiber are important in shaping the microbial ecosystem and have the potential to improve the gut-brain-axis. However, the effects of MACs on neuroinflammation and cognition in an obese condition have not yet been investigated. The present study aimed to evaluate the effect of MACs on the microbiota-gut-brain axis and cognitive function in obese mice induced by a high-fat and fiber deficient (HF-FD) diet. METHODS: C57Bl/6 J male mice were fed with either a control HF-FD or a HF-MAC diet for 15 weeks. Moreover, an additional group was fed with the HF-MAC diet in combination with an antibiotic cocktail (HF-MAC + AB). Following the 15-week treatment, cognitive behavior was investigated; blood, cecum content, colon, and brain samples were collected to determine metabolic parameters, endotoxin, gut microbiota, colon, and brain pathology. RESULTS: We report MACs supplementation prevented HF-FD-induced cognitive impairment in nesting building and temporal order memory tests. MACs prevented gut microbiota dysbiosis, including increasing richness, α-diversity and composition shift, especially in Bacteroidetes and its lower taxa. Furthermore, MACs increased colonic mucus thickness, tight junction protein expression, reduced endotoxemia, and decreased colonic and systemic inflammation. In the hippocampus, MACs suppressed HF-FD-induced neuroglia activation and inflammation, improved insulin IRS-pAKT-pGSK3ß-pTau synapse signaling, in addition to the synaptic ultrastructure and associated proteins. Furthermore, MACs' effects on improving colon-cognitive parameters were eliminated by wide spectrum antibiotic microbiota ablation. CONCLUSIONS: These results suggest that MACs improve cognitive impairments via the gut microbiota-brain axis induced by the consumption of an HF-FD. Supplemental MACs to combat obesity-related gut and brain dysfunction offer a promising approach to prevent neurodegenerative diseases associated with Westernized dietary patterns and obesity.