Tracking investigation of archaeal composition and methanogenesis function from parental to offspring pigs.

Archaea play a crucial role in microbial systems, including driving biochemical reactions and affecting host health by producing methane through hydrogen. The study of swine gut archaea has a positive significance in reducing methane emissions and improving feed utilization efficiency. However, the development and functional changes of archaea in the pig intestines have been overlooked for a long time. In this study, 54 fecal samples were collected from 36 parental pigs (18 boars and 18 pregnant/lactating sows), and 108 fecal samples from 18 offspring pigs during lactation, nursery, growing, and finishing stages were tracked and collected for metagenomic sequencing. We obtained 14 archaeal non-redundant metagenome-assembled genomes (MAGs). These archaea were classified as Methanobacteriota and Thermoplasmatota at the phylum level, and Methanobrevibacter, Methanosphaera, MX-02, and UBA71 at the genus level, involving hydrogenotrophic, methylotrophic, and acetoclastic pathways. The hydrogenotrophic pathway dominated the methanogenesis function, and the vast majority of archaea participated in it. Dietary changes profoundly affected the archaeal composition and methanogenesis function in pigs. The abundance of hydrogen-producing bacteria in parental pigs fed high-fiber diets was higher than that in offspring pigs fed low-fiber diets. The methanogenesis function was positively correlated with fiber decomposition functions and negatively correlated with the starch decomposition function. Increased abundance of sulfate reductase and fumarate reductase, as well as decreased acetate/propionate ratio, indicated that the upregulation of alternative hydrogen uptake pathways competing with methanogens may be the reason for the reduced methanogenesis function. These findings contribute to providing information and direction in the pig industry for the development of strategies to reduce methane emissions, improve feed efficiency, and maintain intestinal health.

Insights into microbial contamination and antibiotic resistome traits in pork wholesale market: An evaluation of the disinfection effect of sodium hypochlorite.

Chlorine and its derivatives, such as sodium hypochlorite (NaClO) and chlorine dioxide, are frequently employed as disinfectants throughout the pork supply chain in China. Nevertheless, the extensive use of NaClO has the potential to cause the creation of 'chlorine-tolerant bacteria' and accelerate the evolution of antibiotic resistance. This study evaluated the efficacy of NaClO disinfection by examining alterations in the microbiome and resistome of a pork wholesale market (PWM), and bacteria isolation and analysis were performed to validate the findings. As expected, the taxonomic compositions of bacteria was significantly different before and after disinfection. Notably, Salmonella enterica (S. enterica), Salmonella bongori (S. bongori), Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Pseudomonas aeruginosa (P. aeruginosa) were observed on all surfaces, indicating that the application of NaClO disinfection treatment in PWM environments for pathogenic bacteria is limited. Correlations were identified between antibiotic resistance genes (ARGs) associated with aminoglycosides (aph(3'')-I, aph(6')-I), quinolone (qnrB, abaQ), polymyxin (arnA, mcr-4) and disinfectant resistance genes (emrA/BD, mdtA/B/C/E/F). Furthermore, correlations were found between risk Rank I ARGs associated with aminoglycoside (aph(3')-I), tetracycline (tetH), beta_lactam (TEM-171), and disinfectant resistance genes (mdtB/C/E/F, emrA, acrB, qacG). Importantly, we found that Acinetobacter and Salmonella were the main hosts of disinfectant resistance genes. The resistance mechanisms of the ARGs identified in PWM were dominated by antibiotic deactivation (38.7%), antibiotic efflux (27.2%), and antibiotic target protection (14.4%). The proportion of genes encoding efflux pumps in the PWM resistome increased after disinfection. Microbial cultures demonstrated that the traits of microbial contamination and antibiotic resistane were consistent with those observed by metagenomic sequencing. This study highlights the possibility of cross-resistance between NaClO disinfectants and antibiotics, which should not be ignored.

Co-exposure to sodium hypochlorite and cadmium induced locomotor behavior disorder by influencing neurotransmitter secretion and cardiac function in larval zebrafish.

Sodium hypochlorite (NaClO) and cadmium (Cd) are widely co-occurring in natural aquatic environment; however, no study has been conducted on effects of their combined exposure on aquatic organisms. To assess effects of exposure to NaClO and Cd in zebrafish larvae, we designed six treatment groups, as follows: control group, NaClO group (300 µg/L), 1/100 Cd group (48 µg/L), 1/30 Cd group (160 µg/L), NaClO+1/100 Cd group, and NaClO+1/30 Cd group analyzed behavior, neurological function and cardiac function. Results revealed that exposure to 1/30 Cd and NaClO+1/30 Cd caused abnormal embryonic development in larvae by altering body morphology and physiological indicators. Combined exposure to NaClO and 1/30 Cd affected the free-swimming activity and behavior of larvae in response to light-dark transition stimuli. Moreover, exposure to 1/30 Cd or NaClO+1/30 Cd resulted in a significant increase in tyrosine hydroxylase and acetylcholinesterase activities, as well as significant changes of various neurotransmitters. Lastly, exposure to 1/30 Cd or NaClO+1/30 Cd influenced the transcription of cardiac myosin-related genes and disturbed the myocardial contractile function. Altogether, our results suggested that combined exposure to NaClO and Cd induced oxidative damage in larvae, resulting in detrimental effects on nervous system and cardiac function, thus altering their swimming behavior.

Longitudinal metagenomic study reveals the dynamics of fecal antibiotic resistome in pigs throughout the lifetime.

BACKGROUND: The dissemination of antibiotic resistance genes (ARGs) poses a substantial threat to environmental safety and human health. Herein, we present a longitudinal paired study across the swine lifetime from birth to market, coupled with metagenomic sequencing to explore the dynamics of ARGs and their health risk in the swine fecal microbiome. RESULTS: We systematically characterized the composition and distribution of ARGs among the different growth stages. In total, 829 ARG subtypes belonging to 21 different ARG types were detected, in which tetracycline, aminoglycoside, and MLS were the most abundant types. Indeed, 134 core ARG subtypes were shared in all stages and displayed a growth stage-associated pattern. Furthermore, the correlation between ARGs, gut microbiota and mobile genetic elements (MGEs) revealed Escherichia coli represented the main carrier of ARGs. We also found that in most cases, the dominant ARGs could be transmitted to progeny piglets, suggesting the potential ARGs generation transmission. Finally, the evaluation of the antibiotic resistance threats provides us some early warning of those high health risk ARGs. CONCLUSIONS: Collectively, this relatively more comprehensive study provides a primary overview of ARG profile in swine microbiome across the lifetime and highlights the health risk and the intergenerational spread of ARGs in pig farm.

Multi-omics analysis reveals the interaction of gut microbiome and host microRNAs in ulcerative colitis.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract that co-occurs with gut microbiota dysbiosis; however, its etiology remains unclear. MicroRNA (miRNA)-microbiome interactions play an essential role in host health and disease. METHODS: To investigate the gut microbiome and host miRNA profiles in colitis, we used a Dextran Sulfate Sodium (DSS)-induced ulcerative colitis (UC) model. Metagenomic sequencing and metabolome profiling were performed to explore typical microbiota and metabolite signatures in colitis, whereas mRNA and miRNA sequencing were used to determine differentially expressed miRNAs and their target genes in the inflamed colon. RESULTS: A total of 986 miRNAs were identified between the two groups, with 41 upregulated and 21 downregulated miRNAs in colitis mice compared to the control group. Notably, the target genes of these significantly altered miRNAs were primarily enriched in the immune and inflammation-related pathways. Second, LEfSe analysis revealed bacterial biomarkers distinguishing the two groups, with significantly higher levels of commonly encountered pathogens such as Escherichia coli and Shigella flexneri in the UC group, whereas beneficial species such as Bifidobacterium pseudolongum were more abundant in the control group. Microbiota metabolites histamine, N-acetylhistamine, and glycocholic acid were found to be downregulated in colitis mice. Spearman correlation further revealed the potential crosstalk between the microbiota profile and colonic miRNA, revealing the possibility of microbiome-miRNA interactions involved in IBD development. CONCLUSIONS: Our data reveal the relationships between multi-omic features during UC and suggest that targeting specific miRNAs may provide new avenues for the development of effective miRNA-based therapeutics.

Longitudinal Investigation of Enteric Virome Signatures from Parental-Generation to Offspring Pigs.

To date, studies on the swine gut microbiome have focused almost exclusively on bacteria. Despite recent advances in the understanding of the swine gut bacteriome at different growth stages, a comprehensive longitudinal study of the lifetime dynamics of the swine gut virome is lacking. Here, we used metagenomic sequencing combined with bioinformatic analysis techniques to characterize the gut viromes of parental-generation and offspring pigs at different biological classification levels. We collected 54 fecal samples from 36 parental-generation pigs (18 breeding boars [Duroc] and 18 pregnant/lactating sows [Landrace]) and 108 fecal samples from 18 offspring pigs during the lactation (day 3), nursery (days 26, 35, and 49), growing (day 120), and finishing (day 180) stages. Alpha diversity, including community richness (richness index) and diversity (Shannon index), showed an overall increasing trend in offspring pigs. Distinct shifts (beta diversity) in the microbiome structure along different growth stages were observed. The linear discriminant analysis effect size (LEfSe) algorithm revealed 53 viral genus that are stage specific. Host prediction results showed that enteric viruses are probably correlated with carbohydrate decomposition. We identified abundant auxiliary carbohydrate-active enzyme (CAZyme) genes from enteric viruses, most of which are glycoside hydrolase genes and participate in the biolysis of complex polysaccharides. IMPORTANCE This study shows that distinct stage-associated swine gut viromes may be determined by age and/or gut physiology at different growth stages, and enteric viruses probably manipulate carbohydrate decomposition by abundant glycoside hydrolases. These findings fill a gap in the longitudinal pattern of the swine gut virome and lay the foundation for research on the function of swine enteric viruses.

Microstructural and functional impairment of the basal ganglia in Wilson's disease: a multimodal neuroimaging study.

Objectives: Magnetic susceptibility changes in brain MRI of Wilson's disease (WD) patients have been described in subcortical nuclei especially the basal ganglia. The objectives of this study were to investigate its relationship with other microstructural and functional alterations of the subcortical nuclei and the diagnostic utility of these MRI-related metrics. Methods: A total of 22 WD patients and 20 healthy controls (HCs) underwent 3.0T multimodal MRI scanning. Susceptibility, volume, diffusion microstructural indices and whole-brain functional connectivity of the putamen (PU), globus pallidus (GP), caudate nucleus (CN), and thalamus (TH) were analyzed. Receiver operating curve (ROC) was applied to evaluate the diagnostic value of the imaging data. Correlation analysis was performed to explore the connection between susceptibility change and microstructure and functional impairment of WD and screen for neuroimaging biomarkers of disease severity. Results: Wilson's disease patients demonstrated increased susceptibility in the PU, GP, and TH, and widespread atrophy and microstructural impairments in the PU, GP, CN, and TH. Functional connectivity decreased within the basal ganglia and increased between the PU and cortex. The ROC model showed higher diagnostic value of isotropic volume fraction (ISOVF, in the neurite orientation dispersion and density imaging model) compared with susceptibility. Severity of neurological symptoms was correlated with volume and ISOVF. Susceptibility was positively correlated with ISOVF in GP. Conclusion: Microstructural impairment of the basal ganglia is related to excessive metal accumulation in WD. Brain atrophy and microstructural impairments are useful neuroimaging biomarkers for the neurological impairment of WD.

Anti-Inflammatory Effect of Clostridium butyricum-Derived Extracellular Vesicles in Ulcerative Colitis: Impact on Host microRNAs Expressions and Gut Microbiome Profiles.

SCORE: Probiotics extracellular vesicles (EVs) have shown potential as EV-based nanomaterials therapy for the treatment of inflammatory bowel disease (IBD). Although probiotic Clostridium butyricum has been reported to be protective in various models of intestinal inflammation, the therapeutic effects of C. butyricum-derived extracellular vesicles (CbEVs) in IBD remain to be demonstrated. METHODS AND RESULTS: In this study, multi-omics sequencing is combined with an in vitro model of lipopolysaccharide-induced RAW264.7 cells and an in vivo mouse model of dextran sodium sulfate-induced colitis to explore the regulatory impact and mechanism of CbEVs in ulcerative colitis. Through small RNA sequencing, the study finds that microRNA is involved in the alleviation of colonic inflammation under CbEVs treatment. Mechanistically, CbEVs restore miR-199a-3p expression, interacting with map3k4, and thereby suppress proinflammatory MAPK and NF-κB signaling. Additionally, metagenomic sequencing demonstrate that CbEVs alleviate bacterial dysbiosis in colitis mice and significantly reduces the abundance of the bacterial pathogens Escherichia coli and Shigella flexneri. Furthermore, CbEVs regulate the microbial tryptophan metabolites, which further improve intestinal barrier integrity and inhibit the inflammatory response in colitis mice. CONCLUSION: C. butyricum-derived extracellular vesicles can be a novel agent for the treatment of colitis and miR-199a-3p can be a potential target for IBD treatment.

Corrigendum: A progression analysis of motor features in Parkinson's disease based on the mapper algorithm.

[This corrects the article DOI: 10.3389/fnagi.2023.1047017.].

Metagenomic Sequencing Identified Specific Bacteriophage Signature Discriminating between Healthy and Diarrheal Neonatal Piglets.

Neonatal diarrhea is one of the most severe diseases in human beings and pigs, leading to high mortality and growth faltering. Gut microbiome-related studies mostly focus on the relationship between bacteria and neonatal diarrhea onset, and no research study has investigated the role of the gut virome in neonatal diarrhea. Here, using metagenomic sequencing, we characterized the fecal viral community of diarrheal and healthy neonatal piglets. We found that the viral community of diarrheal piglets showed higher individual heterogeneity and elevated abundance of Myoviridae. By predicting the bacterial host of the identified viral genomes, phages infecting Proteobacteria, especially E. coli, were the dominant taxa in neonatal diarrheal piglets. Consistent with this, the antibiotic resistance gene of E. coli origin was also enriched in neonatal diarrheal piglets. Finally, we established a random forest model to accurately discriminate between neonatal diarrheal piglets and healthy controls and identified genus E. coli- and genus listeria-infecting bacteriophages, including psa and C5 viruses, as key biomarkers. In conclusion, we provide the first glance of viral community and function characteristics in diarrheal and healthy neonatal piglets. These findings expand our understanding of the relationship among phages, bacteria and diarrhea, and may facilitate the development of therapeutics for the prevention and treatment of neonatal diarrhea.

[Management of helicopter medical transport in 36 patients with critical cardiac disease].

OBJECTIVE: To summarize the management experience of helicopter medical transport in patients with critical heart disease, so as to provide reference for transport of patients with critical heart disease under the background of major natural disasters. METHODS: The clinical and transport data of 36 critically ill cardiac patients in Fuwai Central China Cardiovascular Hospital from 16:30 on July 21 to 19:30 on July 22, 2021 due to historically rare heavy rainstorms were collected. All 36 critically ill cardiac patients were transported by helicopter. The safe transportation was implemented under the measures of quickly forming a transport leadership and coordination group, clarifying responsibilities and division of labor, doing a good job in the pretreatment of the patient's condition, pipeline assessment and mechanical circulation support (MCS) equipment, simulating and practicing the transfer process, improving the safety of the transfer implementation process, and effectively handing over with the target hospital. The gender, age, disease type, MCS, transport and outcome of patients were collected. RESULTS: Thirty-six patients with cardiac critical illness were from adult extracardiac intensive care unit (ICU), adult cardiac care unit (CCU), children's CCU, comprehensive ICU and department of neurology. There were 24 males and 12 females; age (50.93±20.86) years old. There were 12 patients using respirator, 7 patients needing MCS, 2 of whom needed both extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pump (IABP), and 7 patients with post-cardiac surgery. The total distance of transportation of 36 patients was 1 638.4 km, the transit time was 10.5 hours, one way flight time of helicopter was about 8 minutes, and the average transport time per patient was about 17.5 minutes. The vital signs of 36 patients during transport were basically stable, without complications, and all of them reached the target hospital safely. CONCLUSIONS: Under the seamless connection of the rapid establishment of the transfer leadership coordination group, assessment of the patient's condition and pretreatment, the simulation of the transfer process, and the effective handover with the receiving hospital, the use of helicopter for medical transport for critically ill heart patients is feasible and safe, which can buy valuable time for saving patients' lives and further treatment.

How health organizations communicate about COVID-19 on social media: a comparative content analysis.

BACKGROUND: This study examined how different health organizations (i.e., the Chinese CDC, the Korean CDC, the United States CDC, and WHO) communicated about the COVID-19 pandemic on social media, thus providing implications for organizations touse social media effectively in global health crises in the future. METHODS: Three bilingual researchers conducted a content analysis ofsocial media posts (N = 1,343) of these health organizations on Twitter and Sina Weibo to explore the frames of the COVID-19 pandemic, the purposes, and the strategies to communicate about it. RESULTS: Prevention was the dominant frame of the social media content of these four health organizations. Information update was the major communication purpose for WHO, the United States CDC, and the Korean CDC; however, guidance was the primary communication purpose for the Chinese CDC. The United States CDC, the Chinese CDC, and the Korean CDC heavily relied on multiple social media strategies (i.e., visual, hyperlink, and authority quotation) in their communication to the public about the COVID-19 pandemic, whereas WHO primarily employed quoting authorities. Significantdifferences were revealed across these health organizations in frames, communication purposes, and strategies. Theoretical and practical implications and limitations were discussed. CONCLUSIONS: This study examined how different global health organizations communicate about the COVID-19 pandemic on social media. We discussed how and why these global health organizations communicate the COVID-19 pandemic, which would help health-related organizations design messages strategically on global public health issues in the future.

Remote scoring models of rigidity and postural stability of Parkinson's disease based on indirect motions and a low-cost RGB algorithm.

Background and objectives: The Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) is mostly common used for assessing the motor symptoms of Parkinson's disease (PD). In remote circumstances, vision-based techniques have many strengths over wearable sensors. However, rigidity (item 3.3) and postural stability (item 3.12) in the MDS-UPDRS III cannot be assessed remotely since participants need to be touched by a trained examiner during testing. We developed the four scoring models of rigidity of the neck, rigidity of the lower extremities, rigidity of the upper extremities, and postural stability based on features extracted from other available and touchless motions. Methods: The red, green, and blue (RGB) computer vision algorithm and machine learning were combined with other available motions from the MDS-UPDRS III evaluation. A total of 104 patients with PD were split into a train set (89 individuals) and a test set (15 individuals). The light gradient boosting machine (LightGBM) multiclassification model was trained. Weighted kappa (k), absolute accuracy (ACC ± 0), and Spearman's correlation coefficient (rho) were used to evaluate the performance of model. Results: For model of rigidity of the upper extremities, k = 0.58 (moderate), ACC ± 0 = 0.73, and rho = 0.64 (moderate). For model of rigidity of the lower extremities, k = 0.66 (substantial), ACC ± 0 = 0.70, and rho = 0.76 (strong). For model of rigidity of the neck, k = 0.60 (moderate), ACC ± 0 = 0.73, and rho = 0.60 (moderate). For model of postural stability, k = 0.66 (substantial), ACC ± 0 = 0.73, and rho = 0.68 (moderate). Conclusion: Our study can be meaningful for remote assessments, especially when people have to maintain social distance, e.g., in situations such as the coronavirus disease-2019 (COVID-19) pandemic.

A progression analysis of motor features in Parkinson's disease based on the mapper algorithm.

Background: Parkinson's disease (PD) is a neurodegenerative disease with a broad spectrum of motor and non-motor symptoms. The great heterogeneity of clinical symptoms, biomarkers, and neuroimaging and lack of reliable progression markers present a significant challenge in predicting disease progression and prognoses. Methods: We propose a new approach to disease progression analysis based on the mapper algorithm, a tool from topological data analysis. In this paper, we apply this method to the data from the Parkinson's Progression Markers Initiative (PPMI). We then construct a Markov chain on the mapper output graphs. Results: The resulting progression model yields a quantitative comparison of patients' disease progression under different usage of medications. We also obtain an algorithm to predict patients' UPDRS III scores. Conclusions: By using mapper algorithm and routinely gathered clinical assessments, we developed a new dynamic models to predict the following year's motor progression in the early stage of PD. The use of this model can predict motor evaluations at the individual level, assisting clinicians to adjust intervention strategy for each patient and identifying at-risk patients for future disease-modifying therapy clinical trials.

Free-Water Imaging of the Substantia Nigra in GBA Pathogenic Variant Carriers.

BACKGROUND: Pathogenic variants in the glucocerebrosidase gene (GBA) have been identified as the most common genetic risk factor for Parkinson's disease (PD). However, the features of substantia nigra damage in GBA pathogenic variant carriers remain unclear. OBJECTIVE: We aimed to evaluate the microstructural changes in the substantia nigra in non-manifesting GBA pathogenic variant carriers (GBA-NMC) and PD patients with GBA pathogenic variant (GBA-PD) with free-water imaging. METHODS: First, we compared free water values in the posterior substantia nigra between non-manifesting non-carriers (NMNC, n = 29), GBA-NMC (n = 26), and GBA-PD (n = 16). Then, free water values in the posterior substantia nigra were compared between GBA-PD and early- (n = 19) and late-onset (n = 40) idiopathic PD (iPD) patients. Furthermore, we examined whether the baseline free water values could predict the progressions of clinical symptoms. RESULTS: The free water values in the posterior substantia nigra were significantly higher in the GBA-NMC and GBA-PD groups compared to NMNC, and were significantly increased in the GBA-PD group than both early- and late-onset iPD. Free water values in the posterior substantia nigra could predict the progression of anxiety and cognitive decline in GBA-NMC and GBA-PD groups. CONCLUSIONS: We demonstrate that free water values are elevated in the substantia nigra and predict the development of non-motor symptoms in GBA-NMC and GBA-PD. Our findings demonstrate that a significant nigral impairment already exists in GBA-NMC, and nigral injury may be more severe in GBA-PD than in iPD. These results support that free-water imaging can as a potential early marker of substantia nigra damage. © 2023 International Parkinson and Movement Disorder Society.

Extracellular vesicle miRNAs promote the intestinal microenvironment by interacting with microbes in colitis.

Inflammatory bowel disease (IBD) is a global disease with no cure. Disruption of the microbial ecosystem is considered to be an important cause of IBD. Extracellular vesicles (EVs) are vital participants in cell-cell and cell-organism communication. Both host-derived EVs and bacteria-derived membrane vesicles (OMVs) contribute to homeostasis in the intestine. However, the roles of EVs-miRNAs and MVs in host-microbe interactions in colitis remain unclear. In the present study, the animal model of colitis was established by dextran sulfate sodium (DSS) to investigate the changes of miRNAs in colonic EVs from colitis. Several miRNAs were significantly altered in colitis EVs. miR-181b-5p transplantation inhibited M1 macrophage polarization and promoted M2 polarization to reduce the levels of inflammation both in acute and remission of chronic colitis. miR-200b-3p could interact with bacteria and regulate the composition of the microbiota, which contributed to intestinal barrier integrity and homeostasis. Notably, MVs from normal feces could effectively reverse the composition of the intestinal microbiota, restore the intestinal barrier and rescue colitis, and BMVs from colitis would also have similar effects after miR-200b-3p treatment. Our results preliminarily identify a vesicle-based host-microbe interaction cycle in colitis and provide new ideas for colitis treatment.

Liver Transcriptome and Gut Microbiome Analysis Reveals the Effects of High Fructose Corn Syrup in Mice.

High fructose corn syrup (HFCS) is a viscous mixture of glucose and fructose that is used primarily as a food additive. This article explored the effect of HFCS on lipid metabolism-expressed genes and the mouse gut microbiome. In total, ten 3-week-old male C57BL/6J mice were randomly divided into two groups, including the control group, given purified water (Group C) and 30% HFCS in water (Group H) for 16 weeks. Liver and colonic content were collected for transcriptome sequencing and 16S rRNA gene sequencing, respectively. HFCS significantly increased body weight, epididymal, perirenal fat weight in mice (p < 0.05), and the proportion of lipid droplets in liver tissue. The expression of the ELOVL fatty acid elongase 3 (Elovl3) gene was reduced, while Stearoyl-Coenzyme A desaturase 1 (Scd1), peroxisome proliferator activated receptor gamma (Pparg), fatty acid desaturase 2 (Fads2), acyl-CoA thioesterase 2 (Acot2), acyl-CoA thioesterase 2 (Acot3), acyl-CoA thioesterase 4 (Acot4), and fatty acid binding protein 2 (Fabp2) was increased in Group H. Compared with Group C, the abundance of Firmicutes was decreased in Group H, while the abundance of Bacteroidetes was increased, and the ratio of Firmicutes/Bacteroidetes was obviously decreased. At the genus level, the relative abundance of Bifidobacterium, Lactobacillus, Faecalibaculum, Erysipelatoclostridium, and Parasutterella was increased in Group H, whereas that of Staphylococcus, Peptococcus, Parabacteroides, Donghicola, and Turicibacter was reduced in Group H. Pparg, Acot2, Acot3, and Scd1 were positively correlated with Erysipelatoclostridium and negatively correlated with Parabacteroides, Staphylococcus, and Turicibacter. Bifidobacterium was negatively correlated with Elovl3. Overall, HFCS affects body lipid metabolism by affecting the expression of lipid metabolism genes in the liver through the gut microbiome.

Screening of the TMEM151A Gene in Patients With Paroxysmal Kinesigenic Dyskinesia and Other Movement Disorders.

Background: Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder characterized by recurrent involuntary movements usually triggered by sudden movements. Mutations in the TMEM151A gene were found to be the causative factor of PKD in recent studies. It has also been revealed that loss-of-function is the mechanism by which TMEM151A mutations cause PKD. Methods: To investigate the genetic basis of PKD and broaden the clinical spectrum of the TMEM151A mutations, we recruited 181 patients of Chinese origin with movement disorders (MDs), including 39 PRRT2-negative PKD, 3 paroxysmal exercise-induced dyskinesia (PED), 2 paroxysmal non-kinesigenic dyskinesia (PNKD), 127 isolated dystonia, 8 choreas, and 2 myoclonus-dystonia syndromes. Whole-exome sequencing was applied to identify their possible disease-causing mutations. Then, Sanger sequencing was performed for validation and co-segregation analysis. Genetic analysis was also performed on additional family members of patients with TMEM151A mutations. Clinical manifestations of all PKD cases with mutations in TMEM151A reported, so far, were reviewed. Results: Two novel variants of the TMEM151A gene (NM_153266.4, NP_694998.1), c.627_643dup (p.A215Gfs*53) and c.627delG (p.L210Wfs*52), were identified in 2 patients with PKD by whole-exome sequencing and further Sanger sequencing. Both variants were inherited by the patients from their respective mothers. No mutation of the TMEM151A gene was found in the other type of movement disorders. In reviewing the clinical presentation of TMEM151A-related PKD, no statistically significant difference in the age of onset, family history, duration of attacks, laterality, and phenotype was found between genders. More male patients received treatment and had a good response. A higher proportion of female patients did not receive any treatment, possibly because they had a milder condition of the disease. Conclusions: This study further validated the role of TMEM151A in PKD. Future studies on protein function will be needed to ascertain the pathogenesis of TMEM151A in PKD.

Clostridium butyricum and Its Derived Extracellular Vesicles Modulate Gut Homeostasis and Ameliorate Acute Experimental Colitis.

Microbiological treatments are expected to have a role in the future management of inflammatory bowel disease (IBD). Clostridium butyricum (C. butyricum) is a probiotic microorganism that exhibits beneficial effects on various disease conditions. Although many studies have revealed that C. butyricum provides protective effects in mice with colitis, the way C. butyricum establishes beneficial results in the host remains unclear. In this study, we investigated the mechanisms by which C. butyricum modifies the gut microbiota, produces bacterial metabolites that may be involved, and, specifically, how microbial extracellular vesicles (EVs) positively influence IBD, using a dextran sulfate sodium (DSS)-induced colitis murine model in mice. First, we showed that C. butyricum provides a protective effect against colitis, as evidenced by the prevention of body weight loss, a reduction in the disease activity index (DAI) score, a shortened colon length, decreased histology score, and an improved gut barrier function, accompanied by reduced levels of pathogenic bacteria, including Escherichia/Shigella, and an increased relative abundance of butyrate-producing Clostridium sensu stricto-1 and Butyricicoccus. Second, we also confirmed that the gut microbiota and metabolites produced by C. butyricum played key roles in the attenuation of DSS-induced experimental colitis, as supported by the profound alleviation of colitis effects following fecal transplantation or fecal filtrate insertion supplied from C. butyricum-treated mice. Finally, C. butyricum-derived EVs protected the gut barrier function, improved gut microbiota homeostasis in ulcerative colitis, and contributed to overall colitis alleviation. IMPORTANCE This study indicated that C. butyricum provided a prevention effect against colitis mice, which involved protection of the intestinal barrier and positively regulating gut microbiota. Furthermore, we confirmed that the gut microbiota and metabolites that were induced by C. butyricum also contributed to the attenuation of DSS-induced colitis. Importantly, C. butyricum-derived EVs showed an effective impact in alleviating colitis.

PINK1 mediated mitophagy attenuates early apoptosis of gingival epithelial cells induced by high glucose.

BACKGROUND: Oxidative stress mediated by hyperglycemia damages cell-reparative processes such as mitophagy. Down-regulation of mitophagy is considered to be a susceptible factor for diabetes mellitus (DM) and its complications. However, the role of mitophagy in DM-associated periodontitis has not been fully elucidated. Apoptosis of human gingival epithelial cells (hGECs) is one of the representative events of DM-associated periodontitis. Thus, this study aimed to investigate PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy activated in the process of high glucose (HG)-induced hGECs apoptosis. METHODS: For dose-response studies, hGECs were incubated in different concentrations of glucose (5.5, 15, 25, and 50 mmol/L) for 48 h. Then, hGECs were challenged with 25 mmol/L glucose for 12 h and 48 h, respectively. Apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL), caspase 9 and mitochondrial membrane potential (MMP). Subsequently, autophagy was evaluated by estimating P62, LC3 II mRNA levels, LC3 fluorescent puncta and LC3-II/I ratio. Meanwhile, the involvement of PINK1-mediated mitophagy was assessed by qRT-PCR, western blotting and immunofluorescence. Finally, hGECs were transfected with shPINK1 and analyzed by MMP, caspase 9 and annexin V-FITC apoptosis. RESULTS: The number of TUNEL-positive cells and caspase 9 protein were significantly increased in cells challenged with HG (25 mmol/L) for 48 h (HG 48 h). MMP was impaired both at HG 12 h and HG 48 h, but the degree of depolarization was more serious at HG 48 h. The autophagy improved as the amount of LC3 II increased and p62 decreased in HG 12 h. During this process, HG 12 h treatment induced PINK1-mediated mitophagy. PINK1 silencing with HG 12 h resulted in MMP depolarization and cell apoptosis. CONCLUSIONS: These results suggested that loss of the PINK1 gene may cause mitochondrial dysfunction and increase sensitivity to HG-induced apoptosis of hGECs at the early stage. PINK1 mediated mitophagy attenuates early apoptosis of gingival epithelial cells induced by high glucose.