Background:Although alterations in the gut microbiota have been documented in older adults with mild cognitive impairment or physical frailty, the relationship between gut microbiota changes and cognitive frailty (CF) which is a clinical syndrome characterized by the coexistence of physical frailty and mild cognitive impairment in the absence of any dementia, remains unclear. This study aimed to investigate the gut microbial composition associated with CF and to assess the differences between community-dwelling older adults with CF and those without CF using 16S rDNA gene sequencing. Methods:A case-control study was conducted in community-dwelling older adults. Thirty-five older adults with CF and an equal number of older adults without CF were recruited. Fecal samples were examined by 16S rDNA sequencing. Differences in microbial composition at various taxonomic levels between the two groups were identified and evaluated for correlations with cognitive or physical function. Results:The β-diversity differed significantly between the CF and non-CF groups. Several taxa were more abundant in the CF older adults, including the phylum Verrucomicrobia and Tenericutes, the class Verrucomicrobiae and Mollicutes, and three orders (e.g., Verrucomicrobiales), six families (e.g., Akkermansiaceae), and eight genera (e.g., Escherichia-shigella). In contrast, the orders Betaproteobacteriales and Pasteurellales, the families Burkholderiaceae and Pasteurellaceae, and the genera Roseburia and Haemophilus were more abundant in the non-CF older adults (all p < 0.05). Altered gut microbiota effectively discriminated CF older adults well from controls (AUC = 92%). Certain microbiota enriched in the CF older adults, such as Family_XIII and Lactobacillaceae, showed negative correlation with physical performance, while Lactobacillaceae was also negatively correlated with cognitive performance (p < 0.05). conversely, microbiota more abundant in the non-CF older adults, including the genera Roseburia and Burkholderiaceae, were positively correlated with physical performance, and genera Roseburia and Pasteurellaceae were positively correlated with cognitive performance (p < 0.05). Conclusion:This study provides insight into the role of altered gut microbiota in the pathogenesis of CF among community-dwelling older adults. Further longitudinal studies with larger sample sizes are needed to establish causal relationships.
Autism spectrum disorder (ASD) is characterized by social interaction deficits, repetitive behaviors, and restricted interests. Emerging evidence suggests a role for the gut microbiota in ASD pathophysiology, with fecal microbiota transplantation (FMT) emerging as a potential therapeutic strategy. This study investigated the effects of targeted FMT using processed fecal suspensions from rigorously screened healthy human donors, selected by 16S rRNA sequencing for high Lactobacillus abundance, on a propionic acid (PPA)-induced ASD mouse model. PPA-exposed mice exhibited ASD-like behaviors, including anxiety, repetitive grooming, and social interaction deficits, along with alterations in gut microbiota composition, SCFA levels, and neurotransmitter profiles. Donor selection based on 16S rRNA gene sequencing revealed that FMT from donors with high Lactobacillus abundance was more effective in improving social interaction deficits compared to donors with lower Lactobacillus levels. Targeted FMT intervention restored gut microbiota diversity and enriched beneficial taxa, such as Lactobacillus, Roseburia, and Blautia. Furthermore, targeted FMT reduced PPA levels in both feces and the prefrontal cortex (PFC), and normalized the Glu/GABA ratio in the PFC, suggesting a restoration of E/I balance. Electrophysiological recordings confirmed that FMT corrected the E/I imbalance in PFC pyramidal neurons by reducing sEPSC frequency and increasing sIPSC frequency. These findings demonstrate that FMT can ameliorate ASD-like behaviors in a PPA-induced mouse model by modulating gut microbiota and restoring E/I balance in the brain. Our study provides foundational evidence for the potential of targeted FMT as a therapeutic strategy for ASD, highlighting the importance of donor selection based on gut microbiota composition.
Research gaps persist in understanding the interactions between serum 25 (OH)D levels, intestinal fungi, and their metabolites in postmenopausal women. This study, approved by the Ethics Committee of Zhongshan Hospital, Xiamen University, recruited postmenopausal women from Xiamen. Clinical assessments included Body Mass Index (BMI) calculations and blood tests for various bone-related markers using Roche’s electrochemiluminescence system. Bone density was measured via dual-energy X-ray absorptiometry. Fecal DNA was extracted for Internal Transcribed Spacer (ITS) sequencing with a two-stage PCR process and analyzed using high-throughput Illumina sequencing. Metabolites were extracted from fecal samples and analyzed by ultra-high-performance liquid chromatography combined with mass spectrometry. Statistical analyses and data visualization were performed using R, focusing on fungal community structure and correlations with metabolites. The study analyzed 81 postmenopausal women, categorized into vitamin D deficient (VDD), insufficient (VDI), and sufficient (VDS) groups based on serum 25 (OH)D levels. Other health markers, including age and BMI, were consistent across groups. Notably, Linear discriminant analysis identified distinct fungal communities across VDD, VDI, and VDS groups. In the VDD group, notable fungi included Hanseniaspora occidentalis and Pichia. The VDI group showed enrichment of Candida, while the VDS group had higher abundances Such as Phanerochaete, and Nectriaceae. Alpha diversity metrics, such as the Chao1 index, differed significantly among the groups (p < 0.05). Correlation analysis (Spearman) revealed that fungi like Trichosporon and Penicillium positively associated with 25 (OH)D3, whereas fungi such as Cystofilobasidium were negatively correlated with bone mineral density (BMD). Metabolites like Glutaric acid positively correlated with 25 (OH)D3, while l-Citrulline and Deoxycholic acid were negatively correlated. Additionally, Argininosuccinic acid correlated positively with BMD, whereas Acamprosate and p-Hydroxyphenylacetic acid were negatively associated. In postmenopausal women, fungal community composition varies significantly with vitamin D status, potentially correlating with serum 25 (OH)D levels and BMD, indicating that specific fungal species may be relevant for therapeutic strategies with osteoporosis and offering insights into the broader bone health effects of vitamin D.
Background: FZD8 could be a promising therapeutic target in osteoporosis (OP), although the signal transduction mechanism in OP regarding FZD8 has not been completely elucidated. Aims We used the CRISPR/Cas9 technique to develop an Fzd8-knockout mouse model to study whether Fzd8 inactivation results in genetic changes with potential correlations to OP. Materials and Methods: Genotypes of distinguished classified knockout mice, i.e., heterozygous, homozygous, and wild-type were identified through PCR. Applying the murine model, third generation mice were used for the downstream experiments. We investigated the potential relevance of differentially expressed genes (DEGs) in OP. Results: We found that osteoclasts significantly increased in Fzd8-knockout homozygous mice, compared to wild-type mice, while osteoblasts reduced significantly. Before transcription, heterozygous and homozygous mice possessed DEGs related to exons SNP, which are associated with exons CNV. After transcription, DEGs related to exons SNP in heterozygous and homozygous mice were observed, some of which are potentially associated with OP based on pathway and gene set enrichment analyses. Conclusions: Our Fzd8-knockout murine model showed that there were significant alternations in Fzd10 and Lta gene expressions and Itgb3 and RANK protein expressions among the wild-type and homozygous mice, which are significantly associated with bone remodeling. Our results revealed that FZD8 could be a therapeutic target in OP. This study elucidates the molecular mechanisms in OP, providing evidence-based data for OP drug development and treatment. ### Competing Interest Statement The authors have declared no competing interest.
Background:The management of advanced non-small cell lung cancer (NSCLC) after progression on initial immunotherapy represents a significant clinical challenge. Immune checkpoint inhibitor (ICI) rechallenge is a considered option, yet its efficacy remains limited. Strategies to enhance the efficacy of ICI rechallenge are urgently needed. There is a pressing need for novel strategies to sensitize tumors to ICI rechallenge. Previous studies have established a correlation between the gut microbiota and the tumor response to immunotherapy, and have explored the application of fecal microbiota transplantation (FMT) in modifying the immune response by restoring the gut microbiota. However, the potential of FMT from healthy donor to reverse immunotherapy resistance in patients with NSCLC has not been previously investigated. This preliminary study aimed to provide initial insights into the safety, tolerability, and potential efficacy of the combined therapy of FMT from healthy donor with immunotherapy rechallenge in NSCLC patients. Methods:In this single-arm exploratory study, patients with advanced NSCLC who progressed after prior immunotherapy were screened and enrolled based on predefined eligibility criteria, including prior response to ICIs and adequate organ function. Eligible patients received oral FMT capsules from healthy donors followed by rechallenge with camrelizumab. The primary endpoint was safety and feasibility [incidence of adverse events (AEs) graded by CTCAE v5.0]. Secondary end points included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Fecal and blood samples were collected for exploratory analyses of microbiota, metabolome, and T cell receptor (TCR) repertoire. Results:Seven patients (all male, median age 55 years) were enrolled and constituted the analysis population. The majority (5/7) had received three or more prior lines of therapy. During the follow-up period, none experienced grade 4 or higher AEs. The treatment-related AEs were mainly associated with immunotherapy, and only grade 1 FMT-related AEs (e.g., nausea, diarrhea, bloating, and constipation) were reported. One patient achieved a partial response (PR) and one achieved stable disease (SD) with PFS times of 14.6 and 8.1 months, respectively. The median PFS was 1.5 months [95% confidence interval (CI): 1.24-1.75], and the OS was 12.1 months (95% CI: 0.3-23.9) for all patients. Moreover, the treatment modulated the composition of the intestinal flora in all patients, with alpha diversity increasing in responders and decreasing in non-responders. Conclusions:The results indicated that the combined therapy of FMT and immunotherapy rechallenge was feasible and demonstrated a tolerable safety profile in this small cohort. The observed clinical activity is preliminary. These findings support the need for larger, controlled trials to assess the efficacy of this approach.
BackgroundOxidative stress and chronic inflammation play an important role in the pathogenesis process of cognitive frailty (CF). Regular Baduanjin exercise could improve cognitive frailty in older adults, but it is unclear whether the effect of Baduanjin exercise on improving CF is mediated by modulating circulating oxidative stress and inflammatory process.MethodA total of 102 community-dwelling older adults with CF were recruited and randomly allocated into a 24-week Baduanjin exercise training group or no specific exercise intervention control group at an equal rate. Cognitive function and physical frailty index were assessed using the Montreal Cognitive Assessment (MoCA) and the Edmonton Frail Scale (EFS), as well as the oxidative stress and inflammatory cytokines were measured at baseline and after intervention.ResultAfter 24 weeks of intervention, the increased MoCA score (2.51 ± 0.32 points, p < 0.001) and the decreased EFS scores (1.94 ± 0.20 points, p = 0.012) in the Baduanjin group were significantly higher than those in the control group. Serum antioxidant SOD levels were increased by 10.03 ± 4.73 U/mL (p < 0.001), and the prooxidative MDA and 8-iso-PGF2α levels were decreased by −1.08 ± 0.80 nmol/mL (p = 0.030) and −86.61 ± 15.03 ng/L (p < 0.001) in the Baduanjin training group; while inflammatory cytokines IFN-γ, IL-2 and IL-4 levels were increased (1.08 ± 0.33 pg./mL, p = 0.034, 2.74 ± 0.75 pg./mL, p = 0.04 and 1.48 ± 0.35 pg./mL, p = 0.042). In addition, a mediation effect that Baduanjin training improved cognitive ability mediated by an increase of circulating IFN-γ and IL-2 levels were observed in this study.ConclusionRegular Baduanjin exercise training could improve the cognitive frailty of the community-dwelling older adults with CF, and modulate oxidative stress and inflammatory processes by reducing circulating pro-oxidative MDA and 8-iso-PGF2α levels and increasing anti-oxidative SOD levels, as well as impacting inflammatory cytokines IFN-γ, IL-2, and IL-4 levels. Nevertheless, the mechanism of Baduanjin exercise mediating oxidative stress and inflammatory processes should be cautious to be explained.Clinical trial registrationhttp://www.chictr.org.cn/index.aspx, ChiCTR1800020341.
Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer's disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aβ and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD. This work has shown that ErbB4 deficiency increased the burden of Aβ, impaired GABAergic transmission, and disrupted the E/I balance of mitral and tufted cells (M/Ts) in the OB, ultimately resulting in olfactory dysfunction in young adult APP/PS1 mice. NRG1 could enhance GABAergic transmission, rescue E/I imbalance in M/Ts, and alleviate olfactory dysfunction in young adult APP/PS1 mice. OB: olfactory bulb, E/I: excitation/inhibition, Pr: probability of release, PV: parvalbumin interneurons, Aβ: β-amyloid, GABA: gamma-aminobutyric acid.
The iMeta Conference 2024 provides a platform to promote the development of an innovative scientific research ecosystem for microbiome and One Health. The four key components - Technology, Research (Biology), Academic journals, and Social media - form a synergistic ecosystem. Advanced technologies drive biological research, which generates novel insights that are disseminated through academic journals. Social media plays a crucial role in engaging the public and facilitating scientific communication, thus amplifying the impact of research. Together, these elements create a self-sustaining loop that fosters continuous innovation and collaboration in the field of bioinformatics, biotechnology and microbiome research.
BACKGROUND:Senile osteoporosis may be caused by an imbalance in intestinal flora and oxidative stress. Trimethylamine-N-oxide (TMAO), a metabolite of dietary choline dependent on gut microbes, has been found to be significantly increased in osteoporosis. However, the role of TMAO in bone loss during osteoporosis remains poorly understood. In this study, we examined the impact of TMAO on osteoclast differentiation and bone resorption in an in vitro setting. METHODS:Osteoclast differentiation was induced by incubating RAW 264.7 cells in the presence of Receptor Activator for Nuclear Factor-κB Ligand (RANKL) and macrophage-stimulating factor (M-CSF). Flow cytometry, TRAP staining assay, CCK-8, and ELISA were employed to investigate the impact of TMAO on osteoclast differentiation and bone resorption activity in vitro. For mechanistic exploration, RT-PCR and Western blotting were utilized to assess the activation of the NF-κB pathway. Additionally, protein levels of secreted cytokines and growth factors were determined using suspension array technology. RESULTS:Our findings demonstrate that TMAO enhances RANKL and M-CSF-induced osteoclast formation and bone resorption in a dose-dependent manner. Mechanistically, TMAO triggers the upregulation of the NF-κB pathway and osteoclast-related genes (NFATc1, c-Fos, NF-κB p65, Traf6, and Cathepsin K). Furthermore, TMAO markedly elevated the levels of oxidative stress and inflammatory factors. CONCLUSIONS:In conclusion, TMAO enhances RANKL and M-CSF-induced osteoclast differentiation and inflammation in RAW 264.7 cells by activating the NF-κB signaling pathway. These findings offer a new rationale for further academic and clinical research on osteoporosis treatment.
Modulation of gut microbiota by FMT from donors has been applied to the treatment of UC and yielded variable effectiveness in clinical trials. One possibility is that this variable effectiveness was related to donor selection, as a patient’s response to FMT may rely on the capability of the used donor’s microbiota to restore the specific gut disturbances of the patient.
Background: Flat foot deformity is a prevalent and challenging condition often leading to various clinical complications. Accurate identification of abnormal foot types is essential for appropriate interventions. Method: A dataset consisting of 1573 plantar pressure images from 125 individuals was collected. The performance of the You Only Look Once v5 (YOLO-v5) model, improved YOLO-v5 model, and multi-label classification model was evaluated for foot type identification using the collected images. A new dataset was also collected to verify and compare the models. Results: The multi-label classification algorithm based on ResNet-50 outperformed other algorithms. The improved YOLO-v5 model with Squeeze-and-Excitation (SE), the improved YOLO-v5 model with Convolutional Block Attention Module (CBAM), and the multilabel classification model based on ResNet-50 achieved an accuracy of 0.652, 0.717, and 0.826, respectively, which is significantly higher than those obtained using the ordinary plantar-pressure system and the standard YOLO-v5 model. Conclusion: These results indicate that the proposed DL-based multilabel classification model based on ResNet-50 is superior in flat foot type detection and can be used to evaluate the clinical rehabilitation status of patients with abnormal foot types and various foot pathologies when more data on patients with various diseases are available for training.
To explore the efficacy and safety of fecal microbiota transplantation (FMT) as a treatment approach for ulcerative colitis (UC), a comprehensive systematic review and meta-analysis of randomized controlled trials was conducted. To collect and evaluate randomized controlled trials of high quality on FMT for UC, we searched a number of databases, including PubMed, Web of Science, Cochrane, Embase, and Medline, for studies published between the establishment of the databases and March 2023. We conducted a meta-analysis of the studies using Review Manager software (version 5.4.1) to determine the differences in rates of remission and adverse reactions between the FMT group and the control group, utilizing the risk ratio (RR) and 95% confidence interval (CI) to combine our findings. A total of 13 randomized controlled trials (RCTs) on the efficacy of FMT in patients with UC were included in the study, in which 580 patients participated, including 293 patients treated with FMT and 287 control subjects. Meta-analysis revealed that clinical remission was significantly better in the FMT group than in the control group [RR = 1.73; 95% CI = (1.41, 2.12); P < 0.00001]; endoscopic remission was significantly better in the FMT group than in the control group [RR = 1.74; 95% CI = (1.24, 2.44); P = 0.001]. Additionally, there were no significant differences in the incidence of adverse reactions between the two groups [RR = 1.00; 95% CI = (0.86, 1.15); P = 0.96]. Fecal microbiota transplantation has shown potential as a therapeutic intervention for inducing clinical remission in ulcerative colitis UC; nevertheless, the attainment of endoscopic remission and the maintenance of long-term remission continue to present challenges. Safety concerns persist throughout the treatment process, necessitating the implementation of measures to augment both safety and success rates.
Gastrointestinal symptoms are more prevalent in children with autism spectrum disorder (ASD) than in typically developing (TD) children. Constipation is a significant gastrointestinal comorbidity of ASD, but the associations among constipated autism spectrum disorder (C-ASD), microbiota and short-chain fatty acids (SCFAs) are still debated. We enrolled 80 children, divided into the C-ASD group (n = 40) and the TD group (n = 40). In this study, an integrated 16S rRNA gene sequencing and gas chromatography–mass spectrometry-based metabolomics approach was applied to explore the association of the gut microbiota and SCFAs in C-ASD children in China. The community diversity estimated by the Observe, Chao1, and ACE indices was significantly lower in the C-ASD group than in the TD group. We observed that Ruminococcaceae_UCG_002, Erysipelotrichaceae_UCG_003 , Phascolarctobacterium , Megamonas , Ruminiclostridium_5 , Parabacteroides , Prevotella_2 , Fusobacterium , and Prevotella_9 were enriched in the C-ASD group, and Anaerostipes , Lactobacillus , Ruminococcus_gnavus_group , Lachnospiraceae_NK4A136_group , Ralstonia , Eubacterium_eligens_group, and Ruminococcus_1 were enriched in the TD group. The propionate levels, which were higher in the C-ASD group, were negatively correlated with the abundance of Lactobacillus taxa, but were positively correlated with the severity of ASD symptoms. The random forest model, based on the 16 representative discriminant genera, achieved a high accuracy (AUC = 0.924). In conclusion, we found that C-ASD is related to altered gut microbiota and SCFAs, especially decreased abundance of Lactobacillus and excessive propionate in faeces, which provide new clues to understand C-ASD and biomarkers for the diagnosis and potential strategies for treatment of the disorder. This study was registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ; trial registration number ChiCTR2100052106; date of registration: October 17, 2021).
Olfactory dysfunction is among the earliest non-motor symptoms of Parkinson’s disease (PD). As the foremost pathological hallmark, α-synuclein initiates the pathology in the olfactory pathway at the early stage of PD, particularly in the olfactory epithelium (OE) and olfactory bulb (OB). However, the local neural microcircuit mechanisms underlying olfactory dysfunction between OE and OB in early PD remain unknown. We observed that odor detection and discrimination were impaired in 6-month-old SNCA-A53T mice, while their motor ability remained unaffected. It was confirmed that α-synuclein increased and accumulated in OB but not in OE. Notably, the hyperactivity of mitral/tufted cells and the excitation/inhibition imbalance in OB were found in 6-month-old SNCA-A53T mice, which was attributed to the impaired GABAergic transmission and aberrant expression of GABA transporter 1 and vesicular GABA transporter in OB. We further showed that tiagabine, a potent and selective GABA reuptake inhibitor, could reverse the impaired olfactory function and GABAergic signaling in OB of SNCA-A53T mice. Taken together, our findings demonstrate potential synaptic mechanisms of local neural microcircuit underlying olfactory dysfunction at the early stage of PD. These results highlight the critical role of aberrant GABAergic signaling of OB in early diagnosis and provide a potential therapeutic strategy for early-stage PD.
Background and Aims Ulcerative colitis (UC) has become a global public health concern, and is in urgent need of novel therapies. Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been applied to the treatment of UC. Despite its recent successes, it is still largely unknown how FMT functionally modulates the gut microbiota and improves the disease. Methods We prospectively collected fecal samples from the 40 mice (30 mice for dextran sulfate sodium (DSS)-induced, 10 for controls), followed by Propidium monoazide treatment for 16S rRNA gene sequencing. These 30 mice were divided equally into 3 groups, which were transplanted with original donor microbiota (DO), inactivated donor microbiota (DI) and saline, respectively. Subsequently, we used 16S rRNA gene sequencing to analyze the viable gut bacteria of ulcerative colitis (UC) mice and histological analysis to evaluate the effects of fecal microbiota transplantation (FMT) with viable microbiota. Results We demonstrated that the community structure of viable bacteria was significantly different from fecal bacteria based on total DNA. Furthermore, the intestinal viable microbiota and colonic mucosal structure of mice were significantly changed by DSS induction. The histological analysis showed that only the mice treated with original donor microbiota group (HF) achieved a significant improvement. Compared with inactivated donor microbiota group (IF) and saline (NF), Lactobacillus and Halomonas were significantly enriched in the HF group. Conclusion We inferred that only live bacteria from human donor reversed the histopathology and symptoms of UC in mice and altered the gut microbiota. The activity of gut microbiota in donor samples should be considered in FMT and that detailed analysis of viable microbiota is essential to understand the mechanisms by which FMT produces therapeutic effects in the future.
Objective: To systematically assess the association between osteoporosis and cognitive impairment, and to pro-vide new light on the prevention of cognitive impairment in patients with osteoporosis.Method: A comprehensive research of Embase, Cochrane Library, PubMed, Web of Science, CNKI, Wangfang Data and VIP was performed from inception to January 2022, using the search term 'osteoporosis' and 'cognitive impairment'. Literature screening, data extraction and quality evaluation were conducted by two reviewers independently, and meta-analysis was performed by RevMan 5.4 software.Results: A total of 8 studies (136222 participants) were included. Meta-analysis showed that patients with osteoporosis had an increased risk of cognitive impairment [OR=2.01, 95% CI(1.63-2.48), P<0.01]. This initial meta-analysis had significant heterogeneity, and subgroup analysis suggested that potential heterogeneity in different study types, age and outcome indicators.Conclusion: Patients with osteoporosis are at increased risk of cognitive impairment, and osteoporosis inter-vention could prevent or delay the onset of cognitive impairment for those at risk.
Abstract Background: Vitamin D insufficiency or deficiency is associated with an altered microbiota in older men. However, the relationship between the gut microbiota and 25-hydroxyvitamin D (25(OH)D) levels remains unknown in postmenopausal women. In this study, fecal microbiota profiles for 88 postmenopausal women in the high 25(OH)D (HVD) group (n=44) and the low 25(OH)D (LVD) group (n=44) were determined. An integrated 16S rRNA gene sequencing and liquid chromatography–mass spectrometry (LC–MS)-based metabolomics approach was applied to explore the association of serum 25(OH)D levels with the gut microbiota and fecal metabolic phenotype. Adjustments were made using several statistical models for potential confounding variables identified from the literature. Results: The results demonstrated that the community diversity estimated by the Observe, Chao1 and ACE indexes was significantly lower in the LVD group than in the HVD group. Additionally, two kinds of characteristic differences in the microflora were analyzed in the HVD group, and ten kinds of characteristic differences in the microflora were analyzed in the LVD group. We observed that some bacteria belonging to the genera Bifidobacterium, Bacillus, F0332 and Gemella, were enriched in the LVD group, as were other genera, including Lachnoclostridium, UC5_1_2E3, Ruminococcus_gnavus_group and un_f_Lachnospiraceae. Christensenellaceae, Eggerthellaceae and Cloacibacillus were enriched in the HVD group. The L-pyroglutamic acid, inosine, and L-homocysteic acid levels were higher in the HVD group and were negatively correlated with the 1,2-benzenedicarboxylic acid and cholic acid metabolic levels. Conclusions: These observations provide a better understanding of the relationships between serum 25(OH)D levels and the fecal microbiota and metabolites in postmenopausal women.
目的:探究针药并用联合康复训练治疗脑梗死后遗症的临床效果评价.方法:选取2019年4月-2021年5月厦门大学附属中山医院康复医学科收治的96例脑梗死后遗症患者作为研究对象,运用随机数表法将患者随机分成针药组和对照组,每组48例.对照组予常规康复训练,针药组在此基础上予补阳还五汤加减配合针刺回阳九针穴,14 d为1个疗程.以治疗总有效率、改良Barthel指数(MBI)及简化Fugl-Meyer运动功能评分(FMA)为疗效指标.结果:针药组治疗总有效率为97.92%,高于对照组的87.50%;针药组MBI评分为(56.38±6.76)分,高于对照组的(53.14±6.85)分;针药组上、下肢的FMA评分分别为(37.29±6.34)分和(24.69±4.38)分,高于对照组的(31.48±4.27)、(22.34±4.62)分,差异均有统计学意义(P<0.05).结论:针药并用联合康复训练治疗脑梗死后遗症较单纯西医康复方案,更能获得确切疗效,有助于改善肢体功能,提高生活质量.
2021年8月~9月,通过三家开展肠菌移植的单位进行了电子问卷调查,旨在从捐献者的角度,探究我国文化语境下他们对于捐献肠菌的特殊感受和对相关伦理问题的认知态度.结果显示,多数捐献者(80.0%)出于利他的目的进行捐献;超半数捐献者(53.0%)认识到捐献肠菌的风险;61.0%的捐献者同意自己的样本用于未来开放的研究,且后续研究都无需再次同意;与纯粹的捐献相比,具有经济目的的捐献者更加重视肠菌的所有权(χ2=5.73,P<0.05)和利益分享(χ2=10.13,P<0.05).捐献肠菌会引发污名化、隐私权等道德风险,需要提高研究人员的伦理意识,提升民众对生物科学研究的知情权与参与能力,保护公众和个体的利益不被侵犯.
Obesity is a complex chronic, relapsing, progressive disease. Association studies have linked microbiome alterations with obesity and overweight. However, the results are not always consistent. An integrated analysis of 4282 fecal samples (2236 control (normal weight) group, 1152 overweight, and 894 simple obesity) was performed to identify obesity-associated microbial markers. Based on a random effects model and a fixed effects model, we calculated the odds ratios of the metrics, including bacterial alpha-diversity, beta-diversity, Bacteroidetes/Firmicutes ratio, common genera, and common pathways, between the simple obesity and control groups as well as the overweight and control groups. The random forest model was trained based on a single dataset at the genus level. Feature selection based on feature importance ranked by mean decrease accuracy and leave-one-out cross-validation was conducted to improve the predictive performance of the models. Chao1 and evenness possessed significant ORs higher than 1.0 between the obesity and control groups. Significant bacterial community differences were observed between the simple obesity and the control. The ratio of Bacteroidetes/Firmicutes was significantly higher in simple obesity patients. The relative abundance of Lachnoclostridium and Faecalitalea were higher in people with simple obesity, while 23 genera, including Christensenellaceae_R-7_group, Akkermansia, Alistipes, and Butyricimonas, etc., were significantly lower. The random forest model achieved a high accuracy (AUC = 0.83). The adenine and adenosine salvage pathway (PWY-6609) and the L-histidine degradation I pathway (HISDEG-PWY) were clustered in obese patients, while amino acid biosynthesis and degradation pathways (HISDEG-PWY, DAPLYSINESYN-PWY) were decreased. This study identified obesity microbial biomarkers, providing fertile targets for the management of obesity.