Predictors of Mortality in Acute Myocardial Infarction Complicated by Cardiogenic Shock despite Intra-Aortic Balloon Pump: Opportunities for Advanced Mechanical Circulatory Support in Asia.

Introduction: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) mortality remains high despite revascularization and the use of the intra-aortic balloon pump (IABP). Advanced mechanical circulatory support (MCS) devices, such as catheter-based ventricular assist devices (cVAD), may impact mortality. We aim to identify predictors of mortality in AMI-CS implanted with IABP and the proportion eligible for advanced MCS in an Asian population. Methods: We retrospectively analyzed a cohort of Society for Cardiovascular Angiography and Intervention (SCAI) stage C and above AMI-CS patients with IABP implanted from 2017-2019. We excluded patients who had IABP implanted for indications other than AMI-CS. Primary outcome was 30-day mortality. Binary logistic regression was used to calculate adjusted odds ratios (aOR) for patient characteristics. Results: Over the 3-year period, 242 patients (mean age 64.1 ± 12.4 years, 88% males) with AMI-CS had IABP implanted. 30-day mortality was 55%. On univariate analysis, cardiac arrest (p < 0.001), inotrope/vasopressor use prior to IABP (p = 0.004) was more common in non-survivors. Non-survivors were less likely to be smokers (p = 0.001), had lower ejection fraction, higher creatinine/ lactate and lower pH (all p < 0.001). On multi-variate analysis, predictors of mortality were cardiac arrest prior to IABP (aOR 4.00, CI 2.28-7.03), inotrope/vasopressor prior to IABP (aOR 2.41, CI 1.18-4.96), lower arterial pH (aOR 0.02, CI 0.00-0.31), higher lactate (aOR 2.42, CI 1.00-1.19), and lower hemoglobin (aOR 0.83, CI 0.71-0.98). Using institutional MCS criteria, 106 patients (44%) would have qualified for advanced MCS. Conclusions: Early mortality in AMI-CS remains high despite IABP. Many patients would have qualified for higher degrees of MCS.

The prognostic value of metabolic dysfunction-associated steatotic liver disease in acute myocardial infarction: A propensity score-matched analysis.

AIM: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at increased risk of incident cardiovascular disease. However, the clinical characteristics and prognostic importance of MASLD in patients presenting with acute myocardial infarction (AMI) have yet to be examined. METHODS: This study compared the characteristics and outcomes of patients with and without MASLD presenting with AMI at a tertiary centre in Singapore. MASLD was defined as hepatic steatosis, with at least one of five metabolic criteria. Hepatic steatosis was determined using the Hepatic Steatosis Index. Propensity score matching was performed to adjust for age and sex. The Kaplan-Meier curve was constructed for long-term all-cause mortality. Cox regression analysis was used to investigate independent predictors of long-term all-cause mortality. RESULTS: In this study of 4446 patients with AMI, 2223 patients with MASLD were matched with patients without MASLD using propensity scores. The mean follow-up duration was 3.4 ± 2.4 years. The MASLD group had higher rates of obesity, diabetes and chronic kidney disease than their counterparts. Patients with MASLD had early excess all-cause mortality (6.8% vs. 3.6%, p < .001) at 30 days, with unfavourable mortality rates sustained in the long-term (18.3% vs. 14.5%, p = .001) compared with those without MASLD. After adjustment, MASLD remained independently associated with higher long-term all-cause mortality (hazard ratio 1.330, 95% confidence interval 1.106-1.598, p = .002). CONCLUSION: MASLD embodies a higher burden of metabolic dysfunction and is an independent predictor of long-term mortality in the AMI population. Its early identification may be beneficial for risk stratification and provide therapeutic targets for secondary preventive strategies in AMI.

The intestinal digesta microbiota of tropical marine fish is largely uncultured and distinct from surrounding water microbiota.

Studying the gut microbes of marine fishes is an important part of conservation as many fish species are increasingly threatened by extinction. The gut microbiota of only a small fraction of the more than 32,000 known fish species has been investigated. In this study we analysed the intestinal digesta microbiota composition of more than 50 different wild fish species from tropical waters. Our results show that the fish harbour intestinal digesta microbiota that are distinct from that of the surrounding water and that location, domestication status, and host intrinsic factors are strongly associated with the microbiota composition. Furthermore, we show that the vast majority (~97%) of the fish-associated microorganisms do not have any cultured representative. Considering the impact of the microbiota on host health and physiology, these findings underpin the call to also preserve the microbiota of host species, especially those that may be exposed to habitat destruction.

Practical Application of Coronary Physiologic Assessment: Asia-Pacific Expert Consensus Document: Part 1.

Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of evidence that has led to major recommendations in clinical practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region based on updated information in the field that including both wire- and image-based physiologic assessment. This is Part 1 of the whole consensus document, which describes the general concept of coronary physiology, as well as practical information on the clinical application of physiologic indices and novel image-based physiologic assessment.

Practical Application of Coronary Physiologic Assessment: Asia-Pacific Expert Consensus Document: Part 2.

Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of clinical data that has led to major recommendations in all practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region, based on updated information in the field that includes both wire- and image-based physiologic assessment. This is Part 2 of the whole consensus document, which provides theoretical and practical information on physiologic indexes for specific clinical conditions and patient statuses.

Complete genome sequence of Paramuribaculum intestinale DSM 100749T, isolated from feces of C57BL/6 laboratory mice.

Here, the complete genome of Paramuribaculum intestinale type strain DSM 100749T(=JCM 33114T) is presented. P. intestinale is a recently described species of Muribaculaceae and was isolated from the gut of C57BL/6 laboratory mice. The genome can serve as an important resource for comparative genomics approaches.

Trends and predictions of metabolic risk factors for acute myocardial infarction: findings from a multiethnic nationwide cohort.

Background: Understanding the trajectories of metabolic risk factors for acute myocardial infarction (AMI) is necessary for healthcare policymaking. We estimated future projections of the incidence of metabolic diseases in a multi-ethnic population with AMI. Methods: The incidence and mortality contributed by metabolic risk factors in the population with AMI (diabetes mellitus [T2DM], hypertension, hyperlipidemia, overweight/obesity, active/previous smokers) were projected up to year 2050, using linear and Poisson regression models based on the Singapore Myocardial Infarction Registry from 2007 to 2018. Forecast analysis was stratified based on age, sex and ethnicity. Findings: From 2025 to 2050, the incidence of AMI is predicted to rise by 194.4% from 482 to 1418 per 100,000 population. The largest percentage increase in metabolic risk factors within the population with AMI is projected to be overweight/obesity (880.0% increase), followed by hypertension (248.7% increase), T2DM (215.7% increase), hyperlipidemia (205.0% increase), and active/previous smoking (164.8% increase). The number of AMI-related deaths is expected to increase by 294.7% in individuals with overweight/obesity, while mortality is predicted to decrease by 11.7% in hyperlipidemia, 29.9% in hypertension, 32.7% in T2DM and 49.6% in active/previous smokers, from 2025 to 2050. Compared with Chinese individuals, Indian and Malay individuals bear a disproportionate burden of overweight/obesity incidence and AMI-related mortality. Interpretation: The incidence of AMI is projected to continue rising in the coming decades. Overweight/obesity will emerge as fastest-growing metabolic risk factor and the leading risk factor for AMI-related mortality. Funding: This research was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03) and National Medical Research Council Research Training Fellowship (MOH-001131). The SMIR is a national, ministry-funded registry run by the National Registry of Diseases Office and funded by the Ministry of Health, Singapore.

Complete genome sequences of butyrate producing Anaerostipes hadrus strains BA1 and GIF7 isolated from the terminal ileum of a healthy lean male.

Anaerostipes hadrus strains BA1 and GIF7 were isolated from a healthy man. The complete genomes' sizes are 2,946,270 bp (BA1) and 2,907,308 bp (GIF7), with high average nucleotide identity (ANIb = 100%) and alignments ≥96.86% between strains. Conversely, both strains share 97.47% (ANIb) identity and ≤77.36% alignments to A. hadrus ATCC 29173T.

Clinical use of optical coherence tomography during percutaneous coronary intervention and coronary procedures in Southeast Asia: a survey-based expert consensus summary.

Optical coherence tomography (OCT), an established intravascular imaging technique, enables rapid acquisition of high-resolution images during invasive coronary procedures to assist physician decision-making. OCT has utility in identifying plaque/lesion morphology (e.g., thrombus, degree of calcification, and presence of lipid) and vessel geometry (lesion length and vessel diameter) and in guiding stent optimisation through identification of malapposition and underexpansion. The use of OCT guidance during percutaneous coronary interventions (PCI) has demonstrated improved procedural and clinical outcomes in longitudinal registries, although randomised controlled trial data remain pending. Despite growing data and guideline endorsement to support OCT guidance during PCI, its use in different countries is not well established. This article is based on an advisory panel meeting that included experts from Southeast Asia (SEA) and is aimed at understanding the current clinical utility of intracoronary imaging and OCT, assessing the barriers and enablers of imaging and OCT adoption, and mapping a path for the future of intravascular imaging in SEA. This is the first Southeast Asian consensus that provides insights into the use of OCT from a clinician's point of view.

Displaced medial clavicle fractures: a systematic review of outcomes after nonoperative and operative management.

Background: Fractures of the medial clavicle are uncommon. There is no consensus regarding the optimal treatment of displaced medial clavicle fractures. Methods: A systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. PubMed, EMBASE, and the Cochrane Library were queried using the terms medial clavicle and fracture to identify all studies reporting on outcomes following either nonoperative or operative treatment of displaced medial clavicle fractures. Data extracted included patient demographics, fracture classification, surgical technique, patient-reported outcomes, physical, and radiographic findings. Study quality was evaluated using the Methodological Index for Non-Randomized Studies (MINORS) scoring system. Results: The analysis included 15 studies (mean MINORS score, 10 ± 1.5) with a total of 135 patients (85% male, mean age 47 ± 10.9 years [range, 15-87 years]). Five studies (39 patients) reported outcomes following nonoperative treatment. At a mean follow-up of 27 months, there were 5 (13%) symptomatic nonunions, 2 (5%) malunions, and 2 (5%) delayed unions. Eleven studies (96 patients) reported outcomes following surgical treatment with a mean follow-up of 23 months. There were no reported nonunions. Complications included plate prominence/ irritation (30%) and additional surgery was performed for plate removal (27%), fixation failure (3%), and wound débridement (1%). Conclusion: There is limited, low-quality evidence in the literature to guide treatment of displaced medial clavicle fractures. The available data suggest that surgical treatment is associated with good functional outcomes and a lower risk of nonunion and malunion, compared to nonoperative treatment but plate irritation and further surgery to remove the plate was common.

Hepatic steatosis and advanced hepatic fibrosis are independent predictors of long-term mortality in acute myocardial infarction.

AIM: To examine the prevalence and prognosis of hepatic steatosis and fibrosis in post-acute myocardial infarction (AMI) patients. METHODS: Patients presenting with AMI to a tertiary hospital were examined from 2014 to 2021. Hepatic steatosis and advanced hepatic fibrosis were determined using the Hepatic Steatosis Index and fibrosis-4 index, respectively. The primary outcome was all-cause mortality. Cox regression models identified determinants of mortality after adjustments and Kaplan-Meier curves were constructed for all-cause mortality, stratified by hepatic steatosis and advanced fibrosis. RESULTS: Of 5765 patients included, 24.8% had hepatic steatosis, of whom 41.7% were diagnosed with advanced fibrosis. The median follow-up duration was 2.7 years. Patients with hepatic steatosis tended to be younger, female, with elevated body mass index and an increased metabolic burden of diabetes, hypertension and hyperlipidaemia. Patients with hepatic steatosis (24.6% vs. 20.9% mortality, P < .001) and advanced fibrosis (45.6% vs. 32.9% mortality, P < .001) had higher all-cause mortality rates compared with their respective counterparts. Hepatic steatosis (adjusted hazard ratio 1.364, 95% CI 1.145-1.625, P = .001) was associated with all-cause mortality after adjustment for confounders. Survival curves showed excess mortality in patients with hepatic steatosis compared with those without (P = .002). CONCLUSIONS: Hepatic steatosis and advanced fibrosis have a substantial prevalence among patients with AMI. Both are associated with mortality, with an incrementally higher risk when advanced fibrosis ensues. Hepatic steatosis and fibrosis could help risk stratification of AMI patients beyond conventional risk factors.

Coronary CT Angiography-based Morphologic Index for Predicting Hemodynamically Significant Coronary Stenosis.

Purpose To develop a new coronary CT angiography (CCTA)-based index, α×LL/MLD4, that considers lesion entrance angle (α) in addition to lesion length (LL) and minimal lumen diameter (MLD) and to evaluate its efficacy in predicting hemodynamically significant coronary stenosis compared with invasive coronary angiography (ICA)-derived fractional flow reserve (FFR). Materials and Methods This prospective study enrolled participants (September 2016-March 2020) from two centers who underwent CCTA followed by ICA (ClinicalTrials.gov identifier: NCT03054324). CCTA images were processed semiautomatically to measure LL, MLD, and α for calculating α×LL/MLD4. Diagnostic performance and accuracy of α×LL/MLD4 and LL/MLD4 in detecting hemodynamically significant coronary stenosis were compared against the reference standard (invasive FFR ≤ 0.80). Results In total, 133 participants (mean age, 63 years ± 9 [SD]; 99 [74%] men) with 210 stenosed coronary arteries were analyzed. Median α×LL/MLD4 was 54.0 degree/mm3 (IQR, 25.3-128.7) in participants with invasive FFR of 0.80 or less and 6.7 degree/mm3 (IQR, 3.3-12.8) in participants with invasive FFR of more than 0.80 (P < .001). The per-vessel accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for discriminating ischemic lesions were 86.2%, 83.1%, 88.4%, 84.1%, and 87.7% for α×LL/MLD4 and 80.5%, 66.3%, 90.9%, 84.3%, and 78.6% for LL/MLD4, respectively. Area under the receiver operating characteristic curve for discriminating hemodynamically significant stenosis was 0.93 for α×LL/MLD4, which was significantly greater than the values of 0.84 for LL/MLD4 and 0.63 for diameter stenosis (both P < .001). Conclusion The new morphologic index, α×LL/MLD4, incorporating lesion entrance angle achieved higher diagnostic performance in detecting hemodynamically significant lesions compared with diameter stenosis and LL/MLD4. Keywords: CT Angiography, Cardiac, Coronary Arteries, Ischemia, Infarction, Technology Assessment Clinical trial registration no. NCT03054324 Supplemental material is available for this article. © RSNA, 2023 See also the commentary by Fairbairn and Nørgaard in this issue.

Management of glenoid bone loss in primary reverse shoulder arthroplasty : a systematic review and meta-analysis.

AIMS: Rates of reverse total shoulder arthroplasty (rTSA) continue to grow. Glenoid bone loss and deformity remains a technical challenge to the surgeon and may reduce improvements in patients' outcomes. However, there is no consensus as to the optimal surgical technique to best reconstruct these patients' anatomy. This review aims to compare the outcomes of glenoid bone grafting versus augmented glenoid prostheses in the management of glenoid bone loss in primary reverse total shoulder arthroplasty. METHODS: This systematic review and meta-analysis evaluated study-level data in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We performed searches of Medline (Ovid), Embase (Ovid), and PubMed from their dates of inception to January 2022. From included studies, we analyzed data for preoperative and postoperative range of motion (ROM), patient-reported functional outcomes, and complication rates. RESULTS: A total of 13 studies (919 shoulders) were included in the analysis. The mean age of patients at initial evaluation was 72.2 years (42 to 87), with a mean follow-up time of 40.7 months (24 to 120). Nine studies with 292 rTSAs evaluated the use of bone graft and five studies with 627 rTSAs evaluated the use of augmented glenoid baseplates. One study was analyzed in both groups. Both techniques demonstrated improvement in patient-reported outcome measures and ROM assessment, with augmented prostheses outperforming bone grafting on improvements in the American Shoulder and Elbow Surgeons Score. There was a higher complication rate (8.9% vs 3.5%; p < 0.001) and revision rate among the bone grafting group compared with the patients who were treated with augmented prostheses (2.4% vs 0.6%; p = 0.022). CONCLUSION: This review provides strong evidence that both bone graft and augmented glenoid baseplate techniques to address glenoid bone loss give excellent ROM and functional outcomes in primary rTSA. The use of augmented base plates may confer fewer complications and revisions.Cite this article: Bone Joint J 2022;104-B(12):1334-1342.

Trans-interaction of risk loci 6p24.1 and 10q11.21 is associated with endothelial damage in coronary artery disease.

BACKGROUND AND AIMS: Single nucleotide polymorphism rs6903956 has been identified as one of the genetic risk factors for coronary artery disease (CAD). However, rs6903956 lies in a non-coding locus on chromosome 6p24.1. We aim to interrogate the molecular basis of 6p24.1 containing rs6903956 risk alleles in endothelial disease biology. METHODS AND RESULTS: We generated induced pluripotent stem cells (iPSCs) from CAD patients (AA risk genotype at rs6903956) and non-CAD subjects (GG non-risk genotype at rs6903956). CRISPR-Cas9-based deletions (Δ63-89bp) on 6p24.1, including both rs6903956 and a short tandem repeat variant rs140361069 in linkage disequilibrium, were performed to generate isogenic iPSC-derived endothelial cells. Edited CAD endothelial cells, with removal of 'A' risk alleles, exhibited a global transcriptional downregulation of pathways relating to abnormal vascular physiology and activated endothelial processes. A CXC chemokine ligand on chromosome 10q11.21, CXCL12, was uncovered as a potential effector gene in CAD endothelial cells. Underlying this effect was the preferential inter-chromosomal interaction of 6p24.1 risk locus to a weak promoter of CXCL12, confirmed by chromatin conformation capture assays on our iPSC-derived endothelial cells. Functionally, risk genotypes AA/AG at rs6903956 were associated significantly with elevated levels of circulating damaged endothelial cells in CAD patients. Circulating endothelial cells isolated from patients with risk genotypes AA/AG were also found to have 10 folds higher CXCL12 transcript copies/cell than those with non-risk genotype GG. CONCLUSIONS: Our study reveals the trans-acting impact of 6p24.1 with another CAD locus on 10q11.21 and is associated with intensified endothelial injury.

Genome-centric analysis of short and long read metagenomes reveals uncharacterized microbiome diversity in Southeast Asians.

Despite extensive efforts to address it, the vastness of uncharacterized 'dark matter' microbial genetic diversity can impact short-read sequencing based metagenomic studies. Population-specific biases in genomic reference databases can further compound this problem. Leveraging advances in hybrid assembly (using short and long reads) and Hi-C technologies in a cross-sectional survey, we deeply characterized 109 gut microbiomes from three ethnicities in Singapore to comprehensively reconstruct 4497 medium and high-quality metagenome assembled genomes, 1708 of which were missing in short-read only analysis and with >28× N50 improvement. Species-level clustering identified 70 (>10% of total) novel gut species out of 685, improved reference genomes for 363 species (53% of total), and discovered 3413 strains unique to these populations. Among the top 10 most abundant gut bacteria in our study, one of the species and >80% of strains were unrepresented in existing databases. Annotation of biosynthetic gene clusters (BGCs) uncovered more than 27,000 BGCs with a large fraction (36-88%) unrepresented in current databases, and with several unique clusters predicted to produce bacteriocins that could significantly alter microbiome community structure. These results reveal significant uncharacterized gut microbial diversity in Southeast Asian populations and highlight the utility of hybrid metagenomic references for bioprospecting and disease-focused studies.

Long-term outcomes in acute coronary syndrome patients without standard modifiable risk factors: a multi-ethnic retrospective cohort study Of 5400 asian patients.

A sizeable number of patients without standard modifiable cardiovascular risk factors (SMuRFs), such as hypertension, diabetes, hypercholesterolemia and smoking, suffer from acute coronary syndrome (ACS). These SMuRF-less patients have high short-term morbidity and mortality. We compared both short- and long-term outcomes of SMuRF-less and SMuRF ACS patients in a multi-ethnic Asian cohort.This was a retrospective study of patients with first ACS from 2011 to 2017. The primary outcome was long-term all-cause mortality. Secondary outcomes were 30-day all-cause mortality, cardiac-mortality, unplanned cardiac readmission, cardiogenic shock, heart failure, and stroke. Subgroup analysis was carried out by sex and ACS type.Of 5400 patients, 8.6% were SMuRF-less. The median follow-up time was 6.3 years (interquartile range [IQR] 4.2-8.2 years). SMuRF-less patients were younger and tended to present with ST-segment elevation myocardial infarction (STEMI). They were more likely to require inotropic support, intubation, and have cardiac arrest. At 30 days, SMuRF-less patients had higher rates of all-cause mortality, cardiac-related mortality and cardiogenic shock, but lower rates of heart failure. At 6 years, all-cause mortality was similar in both groups (18.0% versus 17.1% respectively, p = 0.631). Kaplan-Meier curves showed increased early mortality in the SMuRF-less group, but the divergence in survival curves was no longer present in the long-term. The absence of SMuRF was an independent predictor of mortality, regardless of sex or ACS type.In a multi-ethnic cohort of patients with ACS, SMuRF-less patients were observed to have higher mortality than SMuRF patients during the early stages which was attenuated over time.

Long-Term Trajectories in Weight and Health Outcomes Following Multidisciplinary Publicly Funded Bariatric Surgery in Patients with Clinically Severe Obesity (≥ 3 Associated Comorbidities): A Nine-Year Prospective Cohort Study in Australia.

Background: Real-world data on long-term (> 5 years) weight loss and obesity-related complications after newer bariatric surgical procedures are currently limited. The aim of this longitudinal study was to examine the effectiveness and sustainability of bariatric surgery in a cohort with clinically severe obesity in a multidisciplinary publicly funded service in two teaching hospitals in New South Wales, Australia. Methods: Patients were adults with complex clinically severe obesity with a BMI ≥ 35 kg/m2 and at least three significant obesity-related comorbidities, who underwent bariatric surgeries between 2009 and 2017. Detailed obesity-related health outcomes were reported from annual clinical data and assessments for up to 9 years of follow-up. Data were also linked with the national joint replacement registry. Results: A total of 65 eligible patients were included (mean, 7; range, 3−12 significant obesity-related comorbidities); 53.8% female; age 54.2 ± 11.2 years, with baseline BMI 52.2 ± 12.5 kg/m2 and weight 149.2 ± 45.5 kg. Most underwent laparoscopic sleeve gastrectomy (80.0%), followed by laparoscopic adjustable gastric banding (10.8%) and one anastomosis gastric bypass (9.2%). Substantial weight loss was maintained over 9 years of follow-up (p < 0.001 versus baseline). Significant total weight loss (%TWL ± SE) was observed (13.2 ± 2.3%) following an initial 1-year preoperative intensive lifestyle intervention, and ranged from 26.5 ± 2.3% to 33.0 ± 2.0% between 1 and 8 years following surgery. Type 2 diabetes mellitus (T2DM), osteoarthritis-related joint pain and depression/severe anxiety were the most common metabolic, mechanical and mental health comorbidities, with a baseline prevalence of 81.5%, 75.4% and 55.4%, respectively. Clinically significant composite cumulative rates of remission and improvement occurred in T2DM (50.0−82.0%) and hypertension (73.7−82.9%) across 6 years. Dependence on continuous positive airway pressure treatment in patients with sleep-disordered breathing fell significantly from 63.1% to 41.2% in 6 years. Conclusion: Bariatric surgery using an intensive multidisciplinary approach led to significant long-term weight loss and improvement in obesity-related comorbidities among the population with clinically complex obesity. These findings have important implications in clinical care for the management of the highest severity of obesity and its medical consequences. Major challenges associated with successful outcomes of bariatric surgery in highly complex patients include improving mental health in the long run and reducing postoperative opioid use. Long-term follow-up with a higher volume of patients is needed in publicly funded bariatric surgery services to better monitor patient outcomes, enhance clinical data comparison between services, and improve multidisciplinary care delivery.

Host Age Prediction from Fecal Microbiota Composition in Male C57BL/6J Mice.

The lifelong relationship between microorganisms and hosts has a profound impact on the overall health and physiology of the holobiont. Microbiome composition throughout the life span of a host remains largely understudied. Here, the fecal microbiota of conventionally raised C57BL/6J male mice was characterized throughout almost the entire adult life span, from "maturing" (9 weeks) until "very old" (112 weeks) age. Our results suggest that microbiota changes occur throughout life but are more pronounced in maturing to middle-age mice than in mice later in life. Phylum-level analysis indicates a shift of the Bacteroidota-to-Firmicutes ratio in favor of Firmicutes in old and very old mice. More Firmicutes amplicon sequence variants (ASVs) were transient with varying successional patterns than Bacteroidota ASVs, which varied primarily during maturation. Microbiota configurations from five defined life phases were used as training sets in a Bayesian model, which effectively enabled the prediction of host age. These results suggest that age-associated compositional differences may have considerable implications for the interpretation and comparability of animal model-based microbiome studies. The sensitivity of the age prediction to dietary perturbations was tested by applying this approach to two age-matched groups of C57BL/6J mice that were fed either a standard or western diet. The predicted age for the western diet-fed animals was on average 27 ± 11 (mean ± standard deviation) weeks older than that of standard diet-fed animals. This indicates that the fecal microbiota-based predicted age may be influenced not only by the host age and physiology but also potentially by other factors such as diet. IMPORTANCE The gut microbiome of a host changes with age. Cross-sectional studies demonstrate that microbiota of different age groups are distinct but do not demonstrate the temporal change that a longitudinal study is able to show. Here, we performed a longitudinal study of adult mice for over 2 years. We identified life stages where compositional changes were more dynamic and showed temporal changes for the more abundant species. Using a Bayesian model, we could reliably predict the life stages of the mice. Application of the same training set to mice fed different dietary regimens revealed that life-stage age predictions were possible for mice fed the same diet but less so for mice fed different diets. This study sheds light on the temporal changes that occur within the gut microbiota of laboratory mice over their life span and may inform researchers on the appropriate mouse age for their research.

Mutual Exclusion of Methanobrevibacter Species in the Human Gut Microbiota Facilitates Directed Cultivation of a Candidatus Methanobrevibacter Intestini Representative.

Methanogenic Archaea (methanogens) are a phylogenetically diverse group of microorganisms and are considered to be the most abundant archaeal representatives in the human gut. However, the gut methanogen diversity of human populations in many global regions remains poorly investigated. Here, we report the abundance and diversity of gut methanogenic Archaea in a multi-ethnic cohort of healthy Singaporeans by using a concerted approach of metagenomic sequencing, 16S rRNA gene amplicon sequencing, and quantitative PCR. Our results indicate a mutual exclusion of Methanobrevibacter species, i.e., the highly prevalent Methanobrevibacter smithii and the less prevalent Candidatus Methanobrevibacter intestini in more than 80% of the samples when using an amplicon sequencing-based approach. Leveraging on this finding, we were able to select a fecal sample to isolate a representative strain, TLL-48-HuF1, for Candidatus Methanobrevibacter intestini. The analyzed physiological parameters of M. smithii DSM 861T and strain TLL-48-HuF1 suggest high similarity of the two species. Comparative genome analysis and the mutual exclusion of the Methanobrevibacter species indicate potentially different niche adaptation strategies in the human host, which may support the designation of Candidatus M. intestini as a novel species. IMPORTANCE Methanogens are important hydrogen consumers in the gut and are associated with differing host health. Here, we determine the prevalence and abundance of archaeal species in the guts of a multi-ethnic cohort of healthy Singapore residents. While Methanobrevibacter smithii is the most prevalent and abundant methanogen in the human gut of local subjects, the recently proposed Candidatus Methanobrevibacter intestini is the abundant methanogen in a minority of individuals that harbor them. The observed potential mutual exclusion of M. smithii and Ca. M. intestini provides further support to the proposal that the two physiologically similar strains may belong to different Methanobrevibacter species.