Metabolic score and its components are associated with carotid plaque prevalence in young adults.

PURPOSE: No study has comprehensively assessed the relationship of metabolic factors including insulin resistance, hypertension, hyperuricemia, and hypercholesterolemia with the development of carotid plaque. Therefore, we constructed metabolic scores based on the above metabolic factors and examined its association with carotid plaque in young and older Chinese adults. METHODS: This study included 17,396 participants who underwent carotid ultrasound examinations, including 14,173 young adults (<65 years) and 3,223 older adults (≥65 years). Individual metabolic score was calculated using triglyceride-glucose (TyG) index, mean arterial pressure (MAP), uric acid, and total cholesterol (TC). Logistic regression models were conducted to examine the role of metabolic score and its components in the prevalence of carotid plaque. The nonlinear relationship was examined using restricted cubic spline regression. Meanwhile, subgroup, interaction, and sensitivity analyses were conducted. RESULTS: The multivariate logistic regression analysis showed that TyG (OR: 1.088; 95%CI: 1.046-1.132), MAP (OR: 1.121; 95%CI: 1.077-1.168), TC (OR: 1.137; 95%CI: 1.094-1.182) and metabolic score (OR: 1.064; 95%CI: 1.046-1.082) were associated with carotid plaque prevalence in young adults rather than older adults. The nonlinear association was not observed for metabolic scores and carotid plaque. Subgroup analyses showed significant associations between metabolic scores and carotid plaque prevalence in men, women, normal-weight, and overweight young adults. No interaction of metabolic score with sex and BMI were observed. CONCLUSIONS: The results support that control of TyG, MAP, TC, and metabolic scores is a key point in preventing the prevalence of carotid plaque in the young adults.

Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China.

BACKGROUND: Within the normal range, elevated alanine aminotransferase (ALT) levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD). AIM: To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively. METHODS: A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected. The incidence rate, cumulative times, and equally and unequally weighted cumulative effects of excess high-normal ALT levels (ehALT) were measured. Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD. RESULTS: A total of 83.13% of participants with MAFLD had normal ALT levels. The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group. Compared with those in the low-normal ALT group, the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651 [95% confidence interval (CI): 1.199-2.273] and 1.535 (95%CI: 1.119-2.106) in the third quartile and 1.616 (95%CI: 1.162-2.246) and 1.580 (95%CI: 1.155-2.162) in the fourth quartile, respectively. CONCLUSION: Most participants with MAFLD had normal ALT levels. Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.

Association between TyG index trajectory and new-onset lean NAFLD: a longitudinal study.

Objective: The purpose of this manuscript is to identify longitudinal trajectories of changes in triglyceride glucose (TyG) index and investigate the association of TyG index trajectories with risk of lean nonalcoholic fatty liver disease (NAFLD). Methods: Using data from 1,109 participants in the Health Management Cohort longitudinal study, we used Latent Class Growth Modeling (LCGM) to develop TyG index trajectories. Using a Cox proportional hazard model, the relationship between TyG index trajectories and incident lean NAFLD was analyzed. Restricted cubic splines (RCS) were used to visually display the dose-response association between TyG index and lean NAFLD. We also deployed machine learning (ML) via Light Gradient Boosting Machine (LightGBM) to predict lean NAFLD, validated by receiver operating characteristic curves (ROCs). The LightGBM model was used to create an online tool for medical use. In addition, NAFLD was assessed by abdominal ultrasound after excluding other liver fat causes. Results: The median age of the population was 46.6 years, and 440 (39.68%) of the participants were men. Three distinct TyG index trajectories were identified: "low stable" (TyG index ranged from 7.66 to 7.71, n=206, 18.5%), "moderate stable" (TyG index ranged from 8.11 to 8.15, n=542, 48.8%), and "high stable" (TyG index ranged from 8.61 to 8.67, n=363, 32.7%). Using a "low stable" trajectory as a reference, a "high stable" trajectory was associated with an increased risk of lean-NAFLD (HR: 2.668, 95% CI: 1.098-6.484). After adjusting for baseline age, WC, SBP, BMI, and ALT, HR increased slightly in "moderate stable" and "high stable" trajectories to 1.767 (95% CI:0.730-4.275) and 2.668 (95% CI:1.098-6.484), respectively. RCS analysis showed a significant nonlinear dose-response relationship between TyG index and lean NAFLD risk (χ2 = 11.5, P=0.003). The LightGBM model demonstrated high accuracy (Train AUC 0.870, Test AUC 0.766). An online tool based on our model was developed to assist clinicians in assessing lean NAFLD risk. Conclusion: The TyG index serves as a promising noninvasive marker for lean NAFLD, with significant implications for clinical practice and public health policy.

A Cohort Study on the Correlation Between Serum Uric Acid Trajectory and New-Onset Hypertension Based on Longitudinal Health Examination Data in Henan Area.

Objective: To explore the correlation between serum uric acid (SUA) trajectories and new-onset hypertension, to provide scientific basis for the prevention and treatment of hypertension. Methods: The study cohort was composed of 4372 subjects who met the inclusion criteria in the cohort study of Henan physical examination population. According to the SUA values of the subjects' physical examination from 2017 to 2019, three different SUA trajectory groups were determined by R LCTM tools, namely low stability group, medium stability group and high stability group. The incidence of hypertension during physical examination in 2020 was followed up, the cumulative incidence rate in each group was calculated by product limit method, and the correlation between different SUA trajectories and new-onset hypertension was analyzed by Cox proportional hazards regression model. Results: The incidence rate of hypertension increased with the increase of SUA locus, which was 4.65%, 9.18% and 12.43% respectively, and the difference was statistically significant (P<0.001). After adjusting multiple confounding factors, such as gender, waist circumference (WC), blood pressure, body mass index (BMI), fasting plasma glucose (FPG) and blood lipid by Cox proportional hazards regression model, the risk of hypertension in SUA medium stability and high stability group was still 1.476 times (95% CI: 1.089~2.000) and 1.692 times (95% CI: 1.152~2.484) of low-stable SUA group (P<0.05). Conclusion: The risk of hypertension increases with the increase of SUA level in the long-term normal range. It is necessary to carry out the intervention for hypertension with long-term normal high value to avoid the progress of hypertension disease, to achieve the purpose of early prevention of hypertension.

Association of the triglyceride-glucose index with the occurrence and recurrence of colorectal adenomas: a retrospective study from China.

BACKGROUND: Resection of colorectal adenoma (CRA) prevents colorectal cancer; however, recurrence is common. We aimed to assess the association of the triglyceride-glucose (TyG) index with CRA occurrence and recurrence. METHODS: Data from 3392 participants at a hospital in China from 2020 to 2022 were analyzed. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A restricted cubic spline was used to fit TyG index dose‒response curves to recurrent adenomas. The discriminatory power of TyG index for predicting later recurrence was assessed with the area under the receiver operating characteristic (ROC) curve in 170 patients with a TyG index at initial adenoma diagnosis. RESULTS: One thousand five hundred ninety-six adenoma and 1465 normal participants were included in the occurrence analysis, and 179 recurrent and 152 nonrecurrent participants were included in the recurrence analysis. The TyG mutation was an independent risk factor for CRA occurrence and recurrence. After adjusting for confounders, the risk of adenoma in the participants in Q2, Q3, and Q4 groups of TyG was 1.324 (95% CI 1.020-1.718), 1.349 (95% CI 1.030-1.765), and 1.445 (95% CI 1.055-1.980) times higher than that of the Q1, respectively, and the risk of recurrence in the Q3 and Q4 groups was 2.267 (95% CI 1.096-4.691) and 2.824 (95% CI 1.199-6.648) times in Q1 group. Multiple logistic regression showed that the highest quartile of the TyG index was associated with a greater risk of advanced adenoma recurrence (OR 4.456, 95% CI 1.157-17.164), two or more adenomas (OR 5.079, 95% CI 1.136-22.714 [after removal of TyG index extreme values]), and proximal colon or both adenomas (OR 3.043, 95% CI 1.186-7.810). Subgroup analysis revealed that the association was found to be present only in participants of all age groups who were either male or without obesity, hyperglycemia, hypertension, or dyslipidemia (p < 0.05). ROC curves illustrated that the TyG index had good predictive efficacy for identifying recurrence, especially for patients with two or more adenomas (AUC 0.777, 95% CI 0.648-0.907). CONCLUSIONS: An increase in the TyG index is associated with an increased risk of adenoma occurrence and recurrence, with a stronger association with the latter.

Effective degradation of phenol by activating PMS with bimetallic Mo and Ni Co-doped g C3N4 composite catalyst: A Fenton-like degradation process promoted by non-free radical 1O2.

The application of bimetal supported graphite phase carbon nitride in activated peroxymonosulfate (PMS) process has become a research hotspot in recent years. In this study, 8-g C3N4/Mo/Ni composite catalyst material was successfully prepared by doping Mo and Ni in graphite phase carbon nitride. The bimetallic active sites were formed in the catalyst, and PMS was activated by the metal valence Mo6+/Mo4+ and Ni2+/Ni(0) through redox double cycle to effectively degrade phenol. When pH was neutral, the degradation rate of 20 mg/L phenol solution with 8-g C3N4/Mo/Ni (0.35 g/L) and PMS (0.6 mM) could reach 95% within 20 min. The degradation rate of 8-g C3N4/Mo/Ni/PMS catalytic system could reach more than 90% within 20min under the condition of pH range of 3-11 and different anions. Meanwhile, the degradation effects of RhB, MB and OFX on different pollutants within 30min were 99%, 100% and 82%, respectively. Electron spin resonance and quenching experiments showed that in 8-g C3N4/Mo/Ni/PMS system, the degradation mechanism was mainly non-free radicals, and the main active species in the degradation process was 1O2. This study provides a new idea for the study of bimetal supported graphite phase carbon nitride activation of PMS and the theoretical study of degradation mechanism.

Efficacy and Safety of Novel Oral Antivirals in Hospitalized COVID-19 Patients: A Network Meta-Analysis of Randomized Clinical Trials.

Objective: Numerous pharmacological interventions are now under investigation for the treatment of the 2019 coronavirus pandemic (COVID-19), and the evidence is rapidly evolving. Our aim is to evaluate the comparative efficacy and safety of these drugs. Methods: We searched for randomized clinical trials (RCTs) on the efficacy and safety of novel oral antivirals for the treatment of hospitalized COVID-19 patients until November 30, 2022, including baricitinib, ivermectin (IVM), favipiravir (FVP), chloroquine (CQ), lopinavir and ritonavir (LPV/RTV), hydroxychloroquine (HCQ), and hydroxychloroquine plus azithromycin (HCQ+AZT). The main outcomes of this network meta-analysis (NMA) were in-hospital mortality, adverse event (AE), recovery time, and improvement in peripheral capillary oxygen saturation (SpO2). For dichotomous results, the odds ratio (OR) was used, and the 95% confidence interval (CI) was determined. We also used meta-regression to explore whether different treatments affected efficacy and safety. STATA 15.0 was used to conduct the NMA. The research protocol was registered with PROSPERO (#CRD 42023415743). Results: Thirty-six RCTs, with 33,555 hospitalized COVID-19 patients, were included in this analysis. First, we compared the efficacy of different novel oral antivirals. Baricitinib (OR 0.56, 95% CI: 0.35 to 0.90) showed the highest probability of being the optimal probiotic species in reducing in-hospital mortality and suggested that none of the interventions reduced AE better than placebo. In terms of safety outcomes, IVM ranked first in improving the recovery time of hospitalized COVID-19 patients (mean difference (MD) -1.36, 95% CI: -2.32 to -0.39). In addition, patients were most likely to increase SpO2 (OR 1.77, 95% CI: 0.09 to 3.45). The meta-regression revealed no significant differences between participants using different novel oral antivirals in all outcomes in hospitalized COVID-19 patients. Conclusion: Currently, baricitinib has reduced in-hospital mortality in hospitalized COVID-19 patients, with moderate certainty of evidence. IVM appeared to be a safer option than placebo in improving recovery time, while FVP was associated with increased SpO2 safety outcomes. These preliminary evidence-based observations should guide clinical practice until more data are made public.

Epidemiological characteristics and dynamic transmissions of COVID-19 pandemics in Chinese mainland: A trajectory clustering perspective analysis.

BACKGROUND: The corona virus disease 2019 (COVID-19) pandemic has spread to more than 210 countries and regions around the world, with different characteristics recorded depending on the location. A systematic summarization of COVID-19 outbreaks that occurred during the "dynamic zero-COVID" policy period in Chinese mainland had not been previously conducted. In-depth mining of the big data from the past two years of the COVID-19 pandemics must be performed to clarify their epidemiological characteristics and dynamic transmissions. METHODS: Trajectory clustering was used to group epidemic and time-varying reproduction number (Rt) curves of mass outbreaks into different models and reveal the epidemiological characteristics and dynamic transmissions of COVID-19. For the selected single-peak epidemic curves, we constructed a peak-point judgment model based on the dynamic slope and adopted a single-peak fitting model to identify the key time points and peak parameters. Finally, we developed an extreme gradient boosting-based prediction model for peak infection cases based on the total number of infections on the first 3, 5, and 7 days of the initial average incubation period. RESULTS: (1) A total of 7 52298 cases, including 587 outbreaks in 251 cities in Chinese mainland between June 11, 2020, and June 29, 2022, were collected, and the first wave of COVID-19 outbreaks was excluded. Excluding the Shanghai outbreak in 2022, the 586 remaining outbreaks resulted in 1 25425 infections, with an infection rate of 4.21 per 1 00000 individuals. The number of outbreaks varied based on location, season, and temperature. (2) Trajectory clustering analysis showed that 77 epidemic curves were divided into four patterns, which were dominated by two single-peak clustering patterns (63.3%). A total of 77 Rt curves were grouped into seven patterns, with the leading patterns including four downward dynamic transmission patterns (74.03%). These curves revealed that the interval from peak to the point where the Rt value dropped below 1 was approximately 5 days. (3) The peak-point judgment model achieved a better result in the area under the curve (0.96, 95% confidence interval = 0.90-1.00). The single-peak fitting results on the epidemic curves indicated that the interval from the slow-growth point to the sharp-decline point was approximately 4-6 days in more than 50% of mass outbreaks. (4) The peak-infection-case prediction model exhibited the superior clustering results of epidemic and Rt curves compared with the findings without grouping. CONCLUSION: Overall, our findings suggest the variation in the infection rates during the "dynamic zero-COVID" policy period based on the geographic division, level of economic development, seasonal division, and temperature. Trajectory clustering can be a useful tool for discovering epidemiological characteristics and dynamic transmissions, judging peak points, and predicting peak infection cases using different patterns.

Efficacy and safety of Omega-3 polyunsaturated fatty acids in adjuvant treatments for colorectal cancer: A meta-analysis of randomized controlled trials.

Background: Colorectal cancer (CRC) ranks third globally. There are many adverse reactions to treatments such as surgeries and post-surgical chemotherapy, which affect patients' prognosis and reduce their life quality. Omega-3 polyunsaturated fatty acids (O3FAs) have become an essential part of immune nutrition due to their anti-inflammatory properties, which improve body immunity and have attracted widespread attention. A systematic review focused on the efficacy and safety of O3FAs for patients undergoing surgeries in combination with chemotherapy or a surgery alone is lacking. Objectives: To evaluate the efficacy of O3FAs in the adjuvant treatment of CRC, a meta-analysis was conducted on patients with CRC who underwent surgeries in combination with chemotherapy or a surgery alone. Methods: As of March 2023, publications have been obtained using search terms from digital databases such as PubMed, Web of Science, Embase and Cochrane Library. Only randomized clinical trials (RCTs) evaluating the efficacy and safety of O3FAs following adjuvant treatments for CRC were included in the meta-analysis. Key outcomes were tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1beta (IL-1ß), albumin, body mass index (BMI), weight, the rate of infectious and non-infectious complications, the length of hospital stay (LOS), CRC mortality and life quality. Results: After screening 1,080 studies, 19 RCTs (n = 1,556) with O3FAs in CRC were included, in all of which at least one efficacy or safety outcome was examined. Compared to the control group, the level of TNF-α (MD = -0.79, 95% CI: 1.51 to -0.07, p = 0.03) and IL-6 was reduced due to O3FA-enriched nutrition during the perioperative period (MD = -4.70, 95% CI: 6.59 to -2.80, p < 0.00001). It also reduces LOS (MD = 9.36, 95% CI: 2.16 to 16.57, p = 0.01). No significant differences were found in CRP, IL-1ß, albumin, BMI, weight, the rate of infectious and non-infectious complications, CRC mortality or life quality. The inflammatory status of patients with CRC undergoing adjuvant therapies decreased after a total parenteral nutrition (TPN) O3FA supplementation (TNF-α, MD = -1.26, 95% CI: 2.25 to -0.27, p = 0.01, I 2 = 4%, n = 183 participants). The rate of infectious and non-infectious complications was reduced among patients with CRC undergoing adjuvant therapies after a parenteral nutrition (PN) O3FA supplementation (RR = 3.73, 95% CI: 1.52 to 9.17, p = 0.004, I 2 = 0%, n = 76 participants). Conclusion: Our observations suggest that supplementation with O3FAs has little or no effect on patients with CRC undergoing adjuvant therapies and that a prolonged inflammatory state may be modified. To validate these findings, well-designed, large-scale, randomized and controlled studies on homogeneous patient populations are expected.

Alterations in the human oral microbiota in systemic lupus erythematosus.

BACKGROUND: Alterations in oral microbiota in patients with systemic lupus erythematosus (SLE) is less evaluated. The aim of this study was to compare the characteristics of the oral microbiome in SLE patients and healthy controls, and construct an SLE classifier based on the oral microbiota. METHODS: We sequenced tongue-coating samples of individuals in treatment-naïve SLE (n = 182) and matched healthy controls (n = 280). We characterized the oral microbiome and constructed a microbial classifier in the derivation cohort and validated the results in the validation cohorts. Furthermore, the oral microbiome of posttreatment SLE (n = 73) was characterized. RESULTS: The oral microbial diversity of SLE was increased, and the microbial community was different between SLE and healthy controls. The genera Prevotella and Veillonella were enriched, while Streptococcus and Porphyromonas were reduced in SLE. In addition, an increase was noted in 27 predicted microbial functions, while a decrease was noted in 34 other functions. Thirty-nine operational taxonomy units (OTUs) were identified to be related with seven clinical indicators. Two OTUs were identified to construct a classifier, which yielded area under the curve values of 0.9166 (95% CI 0.8848-0.9483, p < 0.0001), 0.8422 (95% CI 0.7687-0.9157, p < 0.0001), and 0.8406 (95% CI 0.7677-0.9135, p < 0.0001) in the derivation, validation, and cross-regional validation groups, respectively. Moreover, as disease activity increased, Abiotrophia and Lactobacillales increased, while Phyllobacterium and unclassified Micrococcusaceae decreased. Finally, nine OTUs were selected to construct a classifier distinguishing posttreatment SLE patients from healthy controls, which achieved a diagnostic efficacy of 0.9942 (95% CI 0.9884-1, p < 0.0001). CONCLUSIONS: Our study comprehensively characterizes the oral microbiome of SLE and shows the potential of the oral microbiota as a non-invasive diagnostic biomarker in SLE.

Specially designed yogurt supplemented with combination of pro- and prebiotics relieved constipation in mice and humans.

OBJECTIVE: Functional constipation is a gastrointestinal disorder that affects millions of people and is correlated with gut microbiome dysbiosis. The currently available treatments are ineffective; therefore, novel treatment schemes targeting the gut microbiome are desired. The aim of this study was to assess the effects of yogurt supplemented with seven probiotic strains and six types of dietary fibers on functional constipation. METHODS: In the mouse study, mice with induced constipation were administered the yogurt once a day for 1 wk, with fecal parameters and intestinal transit rate measured. In the clinical study, participants with constipation (N = 86) were given the yogurt once daily (200 g) for 4 wk. Fecal and blood samples along with Patient Assessment of Constipation-symptoms and Patient Assessment of Constipation-Quality of Life Scale questionnaires were collected to evaluate the safety and efficacy of the yogurt. Shotgun metagenomic sequencing was performed to analyze fecal samples of both mice and humans. RESULTS: We found that constipated mice had different gut microbiomes compared with those in healthy controls; yogurt treatment significantly relieved constipation-related symptoms and resulted in shifts in the microbiome. Yogurt also relieved symptoms of antibiotic-induced constipation in mice and restored the gut microbiome to a certain extent. In the clinical trial with 86 patients, yogurt administration significantly improved constipation symptoms and showed no serious adverse effects (was generally considered safe). However, subsequent metagenomic profiling of the gut microbiome did not reveal significant changes in the microbial composition, in contrast to the results in mice. We hypothesize that the differences in dosage between mice and humans may attribute to such discrepancies, and microbiome changes may not be necessary for improvements of constipation symptoms in humans. CONCLUSION: Results from this study showed that yogurt can potentially be used for the treatment of constipation.

Gut microbiome is associated with metabolic syndrome accompanied by elevated gamma-glutamyl transpeptidase in men.

It is predicted that by 2035, metabolic syndrome (MS) will be found in nearly more than half of our adult population, seriously affecting the health of our body. MS is usually accompanied by the occurrence of abnormal liver enzymes, such as elevated gamma-glutamyl transpeptidase (GGT). More and more studies have shown that the gut microbiota is involved in MS; however, the correlation between gut microbiota and MS with elevated GGT has not been studied comprehensively. Especially, there are few reports about its role in the physical examination of the population of men with MS and elevated GGT. By using the whole-genome shotgun sequencing technology, we conducted a genome-wide association study of the gut microbiome in 66 participants diagnosed as having MS accompanied by high levels of GGT (case group) and 66 participants with only MS and normal GGT level (control group). We found that the number of gut microbial species was reduced in participants in the case group compared to that of the control group. The overall microbial composition between the two groups is of significant difference. The gut microbiota in the case group is characterized by increased levels of "harmful bacteria" such as Megamonas hypermegale, Megamonas funiformis, Megamonas unclassified, Klebsiella pneumoniae, and Fusobacterium mortiferum and decreased levels of "beneficial bacteria" such as Faecalibacterium prausnitzii, Eubacterium eligens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bacteroides dorei, and Alistipes putredinis. Moreover, the pathways of POLYAMSYN-PWY, ARG+POLYAMINE-SYN, PWY-6305, and GOLPDLCAT-PWY were also increased in the case group, which may play a role in the elevation of GGT by producing amine, polyamine, putrescine, and endogenous alcohol. Taken together, there are apparent changes in the composition of the gut microbiome in men with MS and abnormal GGT levels, and it is high time to discover specific gut microbiome as a potential therapeutic target in that population. More in-depth studies of relevant mechanism could offer some new methods for the treatment of MS with elevated GGT.

Comparison Of The Gut Microbiota In Different Age Groups In China.

Aging is now the most profound risk factor for almost all non-communicable diseases. Studies have shown that probiotics play a specific role in fighting aging. We used metagenomic sequencing to study the changes in gut microbes in different age groups and found that aging had the most significant effect on subjects' gut microbe structure. Our study divided the subjects (n=614) into two groups by using 50 years as the age cut-off point for the grouping. Compared with the younger group, several species with altered abundance and specific functional pathways were found in the older group. At the species level, the abundance of Bacteroides fragilis, Bifidobacterium longum, Clostridium bolteae, Escherichia coli, Klebsiella pneumoniae, and Parabacteroides merdae were increased in older individuals. They were positively correlated to the pathways responsible for lipopolysaccharide (LPS) biosynthesis and the degradation of short-chain fatty acids (SCFAs). On the contrary, the levels of Barnesiella intestinihominis, Megamonas funiformis, and Subdoligranulum unclassified were decreased in the older group, which negatively correlated with the above pathways (p-value<0.05). Functional prediction revealed 92 metabolic pathways enriched in the older group significantly higher than those in the younger group (p-value<0.05), especially pathways related to LPS biosynthesis and the degradation of SCFAs. Additionally, we established a simple non-invasive model of aging, nine species (Bacteroides fragilis, Barnesiella intestinihominis, Bifidobacterium longum, Clostridium bolteae, Escherichia coli, Klebsiella pneumoniae, Megamonas funiformis, Parabacteroides merdae, and Subdoligranulum unclassified) were selected to construct the model. The area under the receiver operating curve (AUC) of the model implied that supplemented probiotics might influence aging. We discuss the features of the aging microbiota that make it more amenable to pre-and probiotic interventions. We speculate these metabolic pathways of gut microbiota can be associated with the immune status and inflammation of older adults. Health interventions that promote a diverse microbiome could influence the health of older adults.

Comparison of gut microbiota in male MAFLD patients with varying liver stiffness.

Purpose: In this study, we examined the changes to the composition and function of the gut microbiota from patients with metabolic dysfunction-associated fatty liver disease (MAFLD).We compared patients in a case group (liver stiffness (LSM) ≥ 7.4 kPa) with a matched control group (LSM < 7.4 kPa) and investigated the correlation between characteristics of the microbiota and other biochemical indicators. Methods: The study looked at a total of 85 men with MAFLD, 17 of whom were in the case group and 68 of whom were in the control group. We measured waist circumference, blood pressure, and body mass index, as well as clinical parameters including liver stiffness, enzyme levels, cholesterol levels, and fat attenuation. Whole-genome shotgun sequencing technology and the MetaCyc database were then used to detect the composition and major pathways of the gut microbiota for each patient. Statistical analyses were performed, including the chi-square test, the student's t-test, the Wilcoxon rank-sum test, and the Mann-Whitney test. Results: Whole-genome sequencing showed that the composition of the gut microbiota in patients with an LSM of above 7.4 kPa was significantly different to that of the control group. There were seven bacterial species that were different between the two groups. Prevotella copri, Phascolarctobacterium succinatutens, Eubacterium biforme, and Collinsella aerofaciens were enriched in the case group (P < 0.05). Conversely, Bacteroides coprocola, Bacteroides stercoris and Clostridiales bacterium 1_7_47FAA were decreased in the case group (P < 0.05). Furthermore, after removing low abundance pathways, a total of 32 microbial pathways were found to be significantly different between the two groups. Most pathways enriched in the case group over the control were related to biosynthesis of metabolites including amino acids, vitamins, nucleosides, and nucleotides. Conclusion. The composition and function of the gut microbiota in patients with increased liver stiffness are significantly altered. This observation may provide new avenues to better understand the mechanism of liver fibrosis.

Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up.

BACKGROUND: Due to the outbreak and rapid spread of coronavirus disease 2019 (COVID-19), more than 160 million patients have become convalescents worldwide to date. Significant alterations have occurred in the gut and oral microbiome and metabonomics of patients with COVID-19. However, it is unknown whether their characteristics return to normal after the 1-year recovery. METHODS: We recruited 35 confirmed patients to provide specimens at discharge and one year later, as well as 160 healthy controls. A total of 497 samples were prospectively collected, including 219 tongue-coating, 129 stool and 149 plasma samples. Tongue-coating and stool samples were subjected to 16S rRNA sequencing, and plasma samples were subjected to untargeted metabolomics testing. RESULTS: The oral and gut microbiome and metabolomics characteristics of the 1-year convalescents were restored to a large extent but did not completely return to normal. In the recovery process, the microbial diversity gradually increased. Butyric acid-producing microbes and Bifidobacterium gradually increased, whereas lipopolysaccharide-producing microbes gradually decreased. In addition, sphingosine-1-phosphate, which is closely related to the inflammatory factor storm of COVID-19, increased significantly during the recovery process. Moreover, the predictive models established based on the microbiome and metabolites of patients at the time of discharge reached high efficacy in predicting their neutralizing antibody levels one year later. CONCLUSIONS: This study is the first to characterize the oral and gut microbiome and metabonomics in 1-year convalescents of COVID-19. The key microbiome and metabolites in the process of recovery were identified, and provided new treatment ideas for accelerating recovery. And the predictive models based on the microbiome and metabolomics afford new insights for predicting the recovery situation which benefited affected individuals and healthcare.

Alcohol-Related Elevation of Liver Transaminase Is Associated With Gut Microbiota in Male.

Alcoholic liver damage has become a widespread health problem as alcohol consumption increases and is usually identified by elevated liver transaminase. We conducted this study to investigate the role of the gut microbiome in the individual susceptibility to alcoholic liver injury. We divided the participants into four groups based on alcohol consumption and liver transaminase elevation, which were drinking case group, drinking control group, non-drinking case group, and non-drinking control group. The drinking case group meant participants who were alcohol consumers with elevated liver transaminase. We found that alpha and beta diversities of the drinking case group differed from the other three groups. Species Faecalibacterium prausnitzii and Roseburia hominis were significantly in lower abundance in the drinking case group and were proved the protective effect against inflammatory liver damage in the former study. Ruminococcus gnavus exhibited the most positive association to alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and contributed to liver inflammation.

The harmful intestinal microbial community accumulates during DKD exacerbation and microbiome-metabolome combined validation in a mouse model.

Objective: Diabetic kidney disease (DKD) is one of the most prevalent complications of diabetes mellitus (DM) and is associated with gut microbial dysbiosis. We aim to build a diagnostic model to aid clinical practice and uncover a crucial harmful microbial community that contributes to DKD pathogenesis and exacerbation. Design: A total of 528 fecal samples from 180 DKD patients and 348 non-DKD populations (138 DM and 210 healthy volunteers) from the First Affiliated Hospital of Zhengzhou University were recruited and randomly divided into a discovery phase and a validation phase. The gut microbial composition was compared using 16S rRNA sequencing. Then, the 180 DKD patients were stratified into four groups based on clinical stages and underwent gut microbiota analysis. We established DKD mouse models and a healthy fecal microbiota transplantation (FMT) model to validate the effects of gut microbiota on DKD and select the potential harmful microbial community. Untargeted metabolome-microbiome combined analysis of mouse models helps decipher the pathogenetic mechanism from a metabolic perspective. Results: The diversity of the gut microbiome was significantly decreased in DKD patients when compared with that of the non-DKD population and was increased in the patients with more advanced DKD stages. The DKD severity in mice was relieved after healthy gut microbiota reconstruction. The common harmful microbial community was accumulated in the subjects with more severe DKD phenotypes (i.e., DKD and DKD5 patients and DKD mice). The harmful microbial community was positively associated with the serum injurious metabolites (e.g., cholic acid and hippuric acid). Conclusion: The fecal microbial community was altered markedly in DKD. Combining the fecal analysis of both human and animal models selected the accumulated harmful pathogens. Partially recovering healthy gut microbiota can relieve DKD phenotypes via influencing pathogens' effect on DKD mice's metabolism.

The Relationship Between Osteoporosis and Intestinal Microbes in the Henan Province of China.

Osteoporosis (OP) is a chronic disease in the elderly, and China is entering an aging demographic trend. In recent years, increasing evidence has demonstrated that probiotics can treat osteoporosis. This study aimed to explore the relevant mechanisms and to validate the beneficial effect on osteoporosis by high-throughput metagenome-wide gene sequencing in humans. In this study, compared with controls, several species had altered abundances, and specific functional pathways were found in the OP group. At the species level, the species that had increased in OP individuals were positively correlated to bone resorption markers and negatively correlated to 25-OH-D3 and bone formation markers, with Streptococcus sanguinis showing the strongest relevance, followed by Streptococcus gordonii, Actinomyces odontolyticus, and Olsenella unclassified. Additionally, Actinomyces graevenitzii, enriched in the OP group, was positively correlated to inflammation indicators that included white blood cell (WBC), neutrophil count (NEC), and the neutrophil-to-lymphocyte ratio (NLR) (p < 0.05). Conversely, the levels of Akkermansia muciniphila, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides uniformis, and Butyricimonas synergistic were increased in the control group, which had a negative correlation with bone resorption markers and positive correlation with bone formation markers and 25-OH-D3. Additionally, Bacteroides fragilis had a negative correlation with inflammation indicators (WBC, NEC, and NLR) and the above pathways (p < 0.05). Functional prediction revealed that 106 metabolic pathways, enriched in the OP group, were significantly higher than in the control group (p < 0.05). In particular, pathways related to LPS biosynthesis, phytate degradation, lactate acid, and ethanol fermentation were more abundant in the OP group than in the control and were positively related to WBC and NEC. Taken together, several species with altered abundances and specific functional pathways were found in OP individuals. The role of phytases in OP provides novel epidemiological evidence to elucidate the underlying microbiota-relevant mechanisms in bone mineralization and should be explored further.

Structural and Functional Alterations of Gut Microbiota in Males With Hyperuricemia and High Levels of Liver Enzymes.

Objective: To investigate the correlation between the structure and function alterations of gut microbiota and biochemical indicators in males with hyperuricemia (HUA) and high levels of liver enzymes, in order to provide new evidences and therapeutic targets for the clinical diagnosis and treatment of HUA. Methods: A total of 69 patients with HUA (HUA group) and 118 healthy controls were enrolled in this study. Their age, height, waist circumference, weight, and pressure were measured. The clinical parameters such as fasting plasma glucose (FBG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum uric acid (SUA), serum creatinine (Scr), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), white blood cell (WBC), platelet (PLT), and absolute value of neutrophils (NEUT) were examined. We used whole-genome shotgun sequencing technology and HUMAnN2 MetaCyc pathway database to detect the composition and pathways of the gut microbiota. The main statistical methods were student's t test, chi-square tests, and Wilcoxon rank sum test. The correlations among bacterial diversity, microbial pathways, and biochemical indicators were evaluated by the R function "cor.test" with spearman method. Results: The gut bacterial diversity in HUA group reduced significantly and the community of the microbiota was of significant difference between the two groups. The pathways that can produce 5-aminoimidazole ribonucleotide (PWY-6122, PWY-6277, and PWY-6121), aromatic amino acids, and chorismate (COMPLETE-ARO-PWY, ARO-PWY, and PWY-6163) were enriched in the HUA group; while the pathways that can produce short-chain fatty acids (SCFAs, such as CENTFERM-PWY and PWY-6590) and the gut microbiotas that can produce SCFAs (Roseburia hominis, Odoribacter splanchnicus, Ruminococcus callidus, Lachnospiraceae bacterium 3_1_46FAA, Bacteroides uniformis, Butyricimonas synergistica) and equol (Adlercreutzia equolifaciens) were enriched in healthy controls. Conclusion: The structure and function of the gut microbiota in males with HUA and high levels of liver enzymes have altered apparently. In-depth study of related mechanisms may provide new ideas for the treatment of HUA.

Gut Microbiome Alterations in Patients With Carotid Atherosclerosis.

Carotid atherosclerosis (CAS) is a reflection of systemic atherosclerosis and the main pathological processes of cardiovascular disease (CVD), namely, carotid intima-media thickening, carotid plaque formation, and carotid stenosis. Accumulating evidence indicates that the gut microbiota plays an important role in CVD and gut-brain disorders, but the associations of the composition and metabolites of the gut microbiome with CAS have not been studied comprehensively. We performed a gut microbiome genome-wide association study in 31 patients with CAS and 51 healthy controls using whole-genome shotgun sequencing. We found that several risk factors (waist circumference, body mass index, diastolic blood pressure, systolic blood pressure, fasting blood glucose, glycated hemoglobin A1c, total cholesterol, triglyceride, and low-density lipoprotein cholesterol) and inflammatory markers (white blood cell count and absolute value of neutrophils) were significantly higher in the CAS group than in the control group. In addition, 21 species and 142 pathways were enriched in the CAS group, and 10 species and 1 pathway were enriched in the control group. Specifically, Bacteroides eggerthii, Escherichia coli, and Klebsiella pneumoniae were the most abundant species in the CAS group, whereas Parabacteroides unclassified, Prevotella copri, Bacteroides sp 3_1_19, and Haemophilus parainfluenzae were the most abundant species in the control group. Finally, we found that most gut microbes and microbial pathways that were enriched in the CAS group had significant positive correlations with clinical characteristics, whereas the microbes and pathways enriched in healthy controls had significant negative correlations with clinical characteristics excluding high-density lipoprotein cholesterol. In addition, the associations between gut microbes and some microbial pathways (short-chain fatty acid, lipopolysaccharide, and menaquinol biosynthesis) were identified. Our results indicate the existence of a cyclic pathway that elevates the circulating concentrations of trimethylamine-N-oxide in patients with CAS but reduces its concentrations in healthy controls.