Altered diversity and composition of gut microbiota in Chinese patients with chronic pancreatitis

Background/ObjectivesGut microbiota alterations in chronic pancreatitis (CP) are seldomly described systematically. It is unknown whether pancreatic exocrine insufficiency (PEI) and different etiologies in patients with CP are associated with gut microbiota dysbiosis.MethodsThe fecal microbiota of 69 healthy controls (HCs) and 71 patients with CP were compared to investigate gut microbiome alterations in CP and the relationship among gut microbiome dysbiosis, PEI and different etiologies. Fecal microbiomes were analyzed through 16S ribosomal RNA gene profiling, based on next-generation sequencing. Pancreatic exocrine function was evaluated by determining fecal elastase 1 activity.ResultsPatients with CP showed gut microbiota dysbiosis with decreased diversity and richness, and taxa-composition changes. On the phylum level, the gut microbiome of the CP group showed lower Firmicutes and Actinobacteria abundances than the HC group and higher Proteobacteria abundances. The abundances of Escherichia-Shigella and other genera were high in gut microbiomes in the CP group, whereas that of Faecalibacterium was low. Kyoto Encyclopedia of Genes and Genomes pathways (lipopolysaccharide biosynthesis and bacterial invasion of epithelial cells) were predicted to be enriched in the CP group. Among the top 5 phyla and 8 genera (in terms of abundance), only Fusobacteria and Eubacterium rectale group showed significant differences between CP patients, with or without PEI. Correlation analysis showed that Bifidobacterium and Lachnoclostridium correlated positively with fecal elastase 1 (r = 0.2616 and 0.2486, respectively, P < 0.05).ConclusionsThe current findings indicate that patients with CP have gut microbiota dysbiosis that is partly affected by pancreatic exocrine function.     

Soy food intake associates with changes in the metabolome and reduced blood pressure in a gut microbiota dependent manner

Background and aimsConsumption of soy foods has been associated with protection against cardiometabolic disease, but the mechanisms are incompletely understood.We hypothesized that habitual soy food consumption associates with gut microbiome composition, metabolite production, and the interaction between diet, microbiota and metabolites.Methods and resultsWe analyzed dietary soy intake, plasma and stool metabolites, and gut microbiome data from two independent cross-sectional samples of healthy US individuals (N = 75 lean or overweight, and N = 29 obese).Habitual soy intake associated with several circulating metabolites. There was a significant interaction between soy intake and gut microbiome composition, as defined by gut enterotype, on metabolites in plasma and stool. Soy consumption associated with reduced systolic blood pressure, but only in a subset of individuals defined by their gut microbiome enterotype, suggesting that responsiveness to soy may be dependent on microbiome composition. Soy intake was associated with differences in specific microbial taxa, including two taxa mapping to genus Dialister and Prevotella which appeared to be suppressed by high soy intake We identified context-dependent effects of these taxa, where presence of Prevotella was associated with higher blood pressure and a worse cardiometabolic profile, but only in the absence of Dialister.ConclusionsThe gut microbiome is an important intermediate in the interplay between dietary soy intake and systemic metabolism. Consumption of soy foods may shape the microbiome by suppressing specific taxa, and may protect against hypertension only in individuals with soy-responsive microbiota.Clinical trials registryNCT02010359 at clinicaltrials.gov.     

The interplay between the gut microbiota and NLRP3 activation affects the severity of acute pancreatitis in mice

ABSTRACT

Early dysbiosis of the gut microbiota is associated with the severity of acute pancreatitis (AP), although the underlying mechanism is unclear. Here, we investigated the role of crosstalk between NLRP3 and the gut microbiota in the development of AP utilizing gut microbiota deficient mice, as well as NLRP3 knockout (KO) mouse models. Pancreatic damage and systemic inflammation were improved in antibiotic-treated (Abx) and germ-free (GF) mice, accompanied by weakened activity of the intestinal NLRP3 inflammasome. Interestingly, fecal microbiota transplantation (FMT) reactivated the intestinal NLRP3 inflammasome and exacerbated the disease in Abx and GF mice. Although the gut barrier in GF and Abx mice was disrupted, gut microbiota deficiency ameliorated the severity of AP, probably due to the reduction in bacterial translocation from the gut to the pancreas. The composition of the gut microbiota was significantly different between NLRP3 KO mice and wild-type (WT) mice at baseline, and there were alterations in response to the induction of AP. While a dramatic shift in the gut microbiota with overgrowth of Escherichia-Shigella was observed in WT mice suffering from AP, there was no significant change in NLRP3 KO mice with or without AP, suggesting that NLRP3 deficiency counteracts AP-induced microbial disturbance. With a strengthened gut barrier and decreased systemic inflammation, NLRP3 KO mice showed less severe AP, as revealed by reduced pancreatic neutrophilic infiltration and necrosis. Taken together, these results identified the bidirectional modulation between the gut microbiota and NLRP3 in the progression of AP, which suggests the interplay of the host and microbiome during AP.     

Chronic pancreatitis in a caerulein-induced mouse model is associated with an altered gut microbiome

BackgroundChronic pancreatitis (CP) is an inflammatory disease of the pancreas with loss of exocrine/endocrine functions as well as development of fibrosis. Dysbiosis of gut microbiome has been shown to be involved in the pathogenesis of many disease processes. Therefore, we aim to investigate the alteration in gut microbiome associated with CP in caerulein-induced mouse model.MethodsCP was induced in C57Bl/6 by using caerulein injections (50 μg/kg/h, i.p., x7, twice weekly for 10 weeks). Stool samples were collected either one week after end of injection (10-week CP) or 6 weeks (16-week CP). DNA was extracted from stool samples and V4 region of 16S rDNA was sequenced for microbiome analysis.ResultsCP was strongly associated with the alteration in the composition of the gut microbiome, evidenced by differences in α and β diversity. When β diversity was measured using both weighted and unweighted UniFrac distances, stool from control mice is significantly different from mice on 10-week or 16-week CP (q < 0.01). The α-diversity measured by Faith's phylogenetic diversity was lowest in stool from healthy control and highest in stool from mice with 16-week CP (p < 0.001). Bacteria taxa differentially enriched in CP samples were detected using linear discriminant analysis. Bacteria from genera Bifidobacterium, Akkermansia, and Desulfovibrio were enriched in samples from 10-week CP mice. Bacteria from genera Allobaculum, Prevotella, and Bacteroides were enriched in samples from 16-week CP mice.ConclusionTogether, these analyses reveal pronounced alteration in the gut microbiome composition, diversity, and function when mice develop CP.     

Alternations of gut microbiota composition in neonates conceived by assisted reproductive technology and its relation to infant growth

ABSTRACT

The gut microbiome in newborns may be strongly influenced by their intrinsic host microenvironmental factors (e.g., the gestational age) and has been linked to their short-term growth and potentially future health. It is yet unclear whether early microbiota composition is significantly different in newborns conceived by assisted reproductive technology (ART) when compared with those who were conceived spontaneously. Additionally, little is known about the effect of gut microbiota composition on weight gain in early infancy. We aimed to characterize the features and the determinants of the gut microbiome in ART newborns and to assess the impact of early microbiota composition on their weight gain in early infancy in mother-infant dyads enrolled in the China National Birth Cohort (CNBC). Among 118 neonates born by ART and 91 neonates born following spontaneous conception, we observed significantly reduced gut microbiota α-diversity and declined Bacteroidetes relative abundance in ART neonates. The microbiota composition of ART neonates was largely driven by specific ART treatments, hinting the importance of fetus intrinsic host microenvironment on the early microbial colonization. Following up these neonates for six months after their births, we observed the effects of gut microbiome composition on infant rapid weight gaining. Collectively, we identified features and determinants of the gut microbiota composition in ART neonates, and provided evidence for the importance of microbiota composition in neonatal growth.     

Differences in the gut microbiota of women according to ultra-processed food consumption

Background and aimsHigh consumption of ultra-processed food (UPF) has been associated with increased risk of obesity and other metabolic diseases, and this dietary pattern seems to be responsible for chronic changes in the gut microbiota. The aim of this study was to assess the associations of UPF with the gut microbiota and obesity-associated biometrics in women.Methods and resultsThis cross-sectional study examined 59 women. The following parameters were evaluated: food consumption using NOVA classification, anthropometric and metabolic parameters, and gut microbiome by next-generation sequencing. The mean age was 28.0 ± 6.6 years. The mean caloric intake was 1624 ± 531 kcal, of which unprocessed or minimally processed food (G1) accounted for 52.4 ± 13.5%, and UPF accounted for 31.4 ± 13.6%. Leptin levels adjusted for fat mass were negatively associated with G1 and positively associated with UPF. We found 15 species in the gut microbiota that correlated with G1 (3 positively and 12 negatively) and 9 species associated with UPF (5 positively and 4 negatively).ConclusionHigher consumption of UPF was directly associated with leptin resistance, and this study suggests that the consumption of UPF or G1 may affect the composition of the gut microbiota.     

Intra-pancreatic fat deposition across the pancreatitis spectrum and the influence of gut hormones

Background and AimsAcute pancreatitis (AP) and chronic pancreatitis (CP) often represent parts of the spectrum of disease. While growing evidence indicates that intra-pancreatic fat deposition (IPFD) plays an important role in the pathogenesis of pancreatitis, no study of living individuals has investigated IPFD in both AP and CP. Further, the associations between IPFD and gut hormones remain to be elucidated. The aims were to investigate the associations of IPFD with AP, CP, and health; and to study whether gut hormones affect these associations.MethodsMagnetic resonance imaging on the same 3.0 Tesla scanner was used to determine IPFD in 201 study participants. These participants were arranged into the health, AP, and CP groups. Gut hormones (ghrelin, glucagon-like peptide-1, gastric inhibitory peptide, peptide YY, and oxyntomodulin) were measured in blood, both after an 8-hour overnight fasting and after ingestion of a standardised mixed meal. A series of linear regression analyses was run, accounting for age, sex, ethnicity, body mass index, glycated haemoglobin, and triglycerides.ResultsBoth the AP group and CP group had significantly higher IPFD in comparison with the health group, consistently across all models (p for trend 0.027 in the most adjusted model). Ghrelin in the fasted state had a significant positive association with IPFD in the AP group (but not the CP or health group), consistently across all models (p = 0.019 in the most adjusted model). None of the studied gut hormones in the postprandial state was significantly associated with IPFD.ConclusionFat deposition in the pancreas is similarly high in individuals with AP and those with CP. The gut-brain axis, and more specifically overexpression of ghrelin, may contribute to increased IPFD in individuals with AP.     

Effects of 12-week treatment with dapagliflozin and gliclazide on faecal microbiome: Results of a double-blind randomized trial in patients with type 2 diabetes

Aims/hypothesisPatients with type 2 diabetes (T2D) are usually treated with (combinations of) glucose-lowering medication. The effects of these drugs can be influenced by intestinal microbiota and vice versa, as these drugs can also influence microbiome composition. However, as there is currently little clinical insight into this bug–drug interaction, our study aimed to evaluate the effects of 12-week treatment with the SGLT2 inhibitor dapagliflozin and sulphonylurea gliclazide on gut microbiome composition in T2D patients treated with metformin.MethodsA total of 44 patients were randomized to either dapagliflozin or gliclazide treatment for 12 weeks. At baseline and after 12 weeks, faecal samples and 24-h urine were collected. During study visits, anthropometric data were measured and blood samples drawn after an overnight fast. Microbiome composition was determined by 16S rRNA gene sequencing. Plasma glucose, insulin, HbA_1c and urinary glucose excretion were measured using conventional methods.ResultsWhile dapagliflozin and gliclazide similarly improved glycaemic control, dapagliflozin reduced and gliclazide increased fasting insulin. Dapagliflozin also greatly increased urinary glucose excretion whereas gliclazide did not, while body mass index, fat mass percentage and waist circumference were reduced by dapagliflozin, but increased by gliclazide. However, neither treatment significantly affected either gut microbiome alpha diversity or composition and, after treatment, no associations were found between microbiome composition and other clinical parameters.ConclusionEven though gliclazide and dapagliflozin have different metabolic actions in patients with T2D, neither treatment altered the faecal microbiome, thereby suggesting that the observed metabolic changes are not mediated by their effects on the microbiota.     

Probiotics drive gut microbiome triggering emotional brain signatures

ABSTRACT

Experimental manipulation of the gut microbiome was found to modify emotional and cognitive behavior, neurotransmitter expression and brain function in rodents, but corresponding human data remain scarce. The present double-blind, placebo-controlled randomised study aimed at investigating the effects of 4 weeks’ probiotic administration on behavior, brain function and gut microbial composition in healthy volunteers. Forty-five healthy participants divided equally into three groups (probiotic, placebo and no intervention) underwent functional MRI (emotional decision-making and emotional recognition memory tasks). In addition, stool samples were collected to investigate the gut microbial composition. Probiotic administration for 4 weeks was associated with changes in brain activation patterns in response to emotional memory and emotional decision-making tasks, which were also accompanied by subtle shifts in gut microbiome profile. Microbiome composition mirrored self-reported behavioral measures and memory performance. This is the first study reporting a distinct influence of probiotic administration at behavioral, neural, and microbiome levels at the same time in healthy volunteers. The findings provide a basis for future investigations into the role of the gut microbiota and potential therapeutic application of probiotics.     

Integrating tumor genomics into studies of the microbiome in colorectal cancer

ABSTRACT

Although the gut microbiome has been linked to colorectal cancer (CRC) development, associations of microbial taxa with CRC status are often inconsistent across studies. We have recently shown that tumor genomics, a factor that is rarely incorporated in analyses of the CRC microbiome, has a strong effect on the composition of the microbiota. Here, we discuss these results in the wider context of studies characterizing interaction between host genetics and the microbiome, and describe the implications of our findings for understanding the role of the microbiome in CRC.     

Gut microbiota dysbiosis in patients with hepatitis B virus-related cirrhosis

Introduction and aimChronic hepatitis B (CHB) is a global epidemic disease that results from hepatitis B virus (HBV) infection and may progress to liver cirrhosis. The relationship between hepatitis B virus-related cirrhosis (HBV-RC) and gut microbiota dysbiosis is still unclear. The aim of this study is to elucidate the compositional and functional characteristics of the gut microbiota in the patients with liver cirrhosis and healthy individuals.Materials and methodsWe analyzed the gut microbiome in patients with HBV-RC and healthy individuals by 16S rRNA sequencing and metagenomic sequencing of fecal samples. A total of 113 genera, 85 families, 57 orders, 44 classes and 21 phyla were performed.ResultsOur results suggests that the composition of the gut microbiota had changed in the early stages of cirrhosis. We further identified more than 17 genera with different richness in compensated and decompensated cirrhosis groups. PICRUSt analysis showed that changes in bacterial composition can lead to significant changes in gene function, which may be one of the causes of liver cirrhosis.ConclusionOur study demonstrated that the composition of gut microbiota changed at different phases of HBV-RC. Gut microbiome transformation may be a biological factor in the progression of cirrhosis.     

Diet and Gut Microbial Function in Metabolic and Cardiovascular Disease Risk

Over the past decade, the gut microbiome has emerged as a novel and largely unexplored source of variability for metabolic and cardiovascular disease risk, including diabetes. Animal and human studies support several possible pathways through which the gut microbiome may impact health, including the production of health-related metabolites from dietary sources. Diet is considered important to shaping the gut microbiota; in addition, gut microbiota influence the metabolism of many dietary components. In the present paper, we address the distinction between compositional and functional analysis of the gut microbiota. We focus on literature that highlights the value of moving beyond surveys of microbial composition to measuring gut microbial functioning to delineate mechanisms related to the interplay between diet and gut microbiota in cardiometabolic health.     

Microbial modulation of the gut microbiome for treating autoimmune diseases

ABSTRACT

Introduction: Many studies have shown the relationship between autoimmune diseases and the gut microbiome in humans: those with autoimmune conditions display gut microbiome dysbiosis. The big question that needs to be addressed is if restoring eubiosis of the gut microbiota can help suppress the autoimmune condition by activating various immune regulatory mechanisms. Inducing these self-healing mechanisms should prolong good health in affected individuals.

Area covered: Here, we review the available clinical and preclinical studies that have used selective bacteria for modulating gut microbiota for treating autoimmune diseases. The potential bacterial candidates and their mechanism of action in treating autoimmune diseases will be discussed. We searched for genetically modified and potential probiotics for diseases and discuss the most likely candidates.

Expert commentary: To achieve eubiosis, manipulation of the gut microbiota must occur in some form. Several approaches for modulating gut microbiota include prebiotic diets, antimicrobial interventions, fecal microbiota transplants, and selective probiotics. One novel approach showing promising results is the use of selective bacterial candidates to modulate microbial composition. Use of single microbe for treatment has an advantage as compared to multi-species as microbes grow at different rates and if needed, a single microbe is easy to target.     

Gut microbiome in acute pancreatitis: A review based on current literature

The gut microbiome is a complex microbial community, recognized for its potential role in physiology, health, and disease. The available evidence supports the role of gut dysbiosis in pancreatic disorders, including acute pancreatitis (AP). In AP, the presence of gut barrier damage resulting in increased mucosal permeability may lead to translocation of intestinal bacteria, necrosis of pancreatic and peripancreatic tissue, and infection, often accompanied by multiple organ dysfunction syndrome. Preserving gut microbial homeostasis may reduce the systemic effects of AP. A growing body of evidence suggests the possible involvement of the gut microbiome in various pancreatic diseases, including AP. This review discusses the possible role of the gut microbiome in AP. It highlights AP treatment and supplementation with prebiotics, synbiotics, and probiotics to maintain gastrointestinal microbial balance and effectively reduce hospitalization, morbidity and mortality in an early phase. It also addresses novel therapeutic areas in the gut microbiome, personalized treatment, and provides a roadmap of human microbial contributions to AP that have potential clinical benefit.     

Endoscopic sphincterotomy (ES) may not alter the natural history of idiopathic recurrent acute pancreatitis (IRAP)

BackgroundThe role of endoscopic sphincterotomy (ES) in idiopathic recurrent acute pancreatitis (IRAP) is unclear. We hypothesized that ES will alter the natural history of IRAP.MethodsWe retrospectively studied the course of 50 IRAP patients from the NAPS2 study from UPMC based on whether they underwent ES or were managed medically. Data included age at first AP, rate of attacks, and history of severe AP. Primary outcomes were any subsequent AP and rate of attacks; secondary outcome was chronic pancreatitis (CP) diagnosis during follow-up. Similar data was abstracted for alcoholic RAP.ResultsWhen compared with medically managed IRAP patients (n = 24, 48%), those who underwent ES (n = 26, 52%) had similar rate of attacks/year (median 1.54 vs. 1.41, p = 0.63), but significantly more attacks (median 3 vs. 2, p = 0.04) at baseline. During follow-up (median 7 years), rate of attacks/year decreased significantly, and were similar in both groups (median 0.16 vs. 0, p = ns). Predictors for rate of attacks during follow-up were sex (ratio 0.54 in females, p = 0.045) and rate of attacks at baseline (ratio for doubling 1.2, p = 0.025), but not ES. Alcoholic RAP patients had lower rate of attacks at baseline, but higher risk of subsequent AP (80 vs. 46%, p = 0.021) and rate of attacks/year (median 0.25 vs. 0, p = 0.016) during follow-up. Progression to CP occurred in IRAP and ES, medically managed IRAP, and alcoholic RAP in 27%, 8% and 27% respectively (p = ns).ConclusionsES, chosen in patients with higher burden of attacks, does not seem to impact the natural history of IRAP.     

Factors associated with prior acute pancreatitis episodes among patients with chronic pancreatitis

BackgroundThe relationship between chronic pancreatitis (CP) and acute pancreatitis (AP) is complex and not well understood. CP could be preceded by antecedent episodes of AP.AimsThe aim of this study was to explore both genetic and environmental factors associated with AP episodes before the diagnosis of CP.MethodsThis was a cross-sectional study including 1022 patients. Detailed demographic, genetic, and clinical data were collected. Based on the presence of AP episode(s) before diagnosis of CP, patients were divided into AP group (further classified into single episode of AP group and recurrent AP group) and non-AP group. Related factors among these groups were assessed using multivariate logistic regression model.ResultsBefore diagnosis of CP, 737 patients (72.1%) had a history of AP. Smoking(P = 0.005) and heavy alcohol consumption(P = 0.002) were risk factors for AP while age at CP onset(P < 0.001), harboring the SPINK1 mutation(P < 0.001), diabetes(P < 0.001) and steatorrhea(P < 0.001) were protective factors. Further, alcoholic CP(P = 0.019) was the only independent risk factor for recurrent AP attacks while age at onset of CP(P < 0.001), pancreatic stones(P = 0.024). and pseudocysts(P = 0.018) served as protective factors.ConclusionsSPINK1 mutations served as protective factor for AP episodes, suggesting SPINK1 mutation might play a pathogenic role in CP occurrence with occult clinical manifestations.     

Compositional and functional alterations of gut microbiota in patients with stroke

Background and aimsThere is accumulating evidence that gut microbiota plays a key role in cardiovascular diseases. Gut bacteria can transform dietary choline, l-carnitine, and trimethylamine N-oxide (TMAO) into trimethylamine, which can be oxidized into TMAO again in the liver. However, the alterations of the gut microbiota in large artery atherosclerotic (LAA) stroke and cardioembolic (CE) stroke have been less studied.Methods and resultsWe performed a case–control study in patients with LAA and CE types of strokes. We profiled the gut microbiome using Illumina sequencing of the 16S ribosomal RNA gene (V4–V5 regions), and TMAO was determined via liquid chromatography–tandem mass spectrometry. Our results showed that the TMAO levels in the plasma of patients with LAA and CE strokes were significantly higher than those in controls (LAA stroke, 2931 ± 456.4 ng/mL; CE stroke, 4220 ± 577.6 ng/mL; healthy control, 1663 ± 117.8 ng/mL; adjusted p < 0.05). The TMAO level in the plasma of patients with LAA stroke was positively correlated with the carotid plaque area (rho = 0.333, 95% CI = 0.08–0.55, p = 0.0093). Notably, the composition and the function of gut microbiota in the LAA stroke group were significantly different from those in the control group (FDR-adjusted p-value < 0.05). There was no significant association between gut microbiota and CE stroke in our study.ConclusionThis study provides evidence for significant compositional and functional alterations of the gut microbiome in patients with LAA stroke. Gut microbiota might serve as a potential biomarker for patients with LAA stroke.     

Factors that drive variation among gut microbial communities

Surveys of humans from around the world have revealed differences in gut microbiota composition among geographically separated populations. But because humans from the same regions often share common ancestry as well as dietary and cultural habits, most studies have not been able to differentiate among the effects of heritable factors and external factors on the composition of the gut microbiota. Here we discuss how the analysis of gut microbial communities of chimpanzees residing in Gombe Stream National Park has provided an unprecedented opportunity to measure the effects of external factors while controlling for heritable factors. The differences in gut microbiota composition between separated host populations of chimpanzees are due almost entirely to external factors, with the contribution of heritable factors to intraspecific variation in gut microbiota composition being too small to detect. The dominant influence of external factors in generating differences among the gut microbiota of our closest relatives lends promise to the possibility of manipulating the composition of the gut microbiome within human hosts. These results highlight the need for controlled studies that isolate the roles of specific external factors, such as diet, cultural practices and geography, in generating differences in the gut microbiota composition.     

The gut microbial influence on cholestatic liver disease

Patients with cholestatic liver diseases like primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) have a different gut microbiome composition than healthy controls. In contrast with PBC, PSC has a strong association with inflammatory bowel disease and is the prototypical disease of the gut‐liver axis. Still, there are some distinct overlapping microbial features in the microbiome of patients with PSC and PBC suggesting similarities in cholestatic diseases, although the possible pathogenetic involvement of these shared microbial changes is unknown. Herein, we present an overview of the available data and discuss the relevance for potential disease relevant host‐microbiota interactions. In general, the microbiome interacts with the host via the immunobiome (interactions between the host immune system and the gut microbiome), the endobiome (where the gut microbiome contributes to host physiology by producing or metabolizing endogenous molecules) and the xenobiome (gut microbial transformation of exogenous compounds, including nutrients and drugs). Experimental and human observational evidence suggest that the presence and functions of gut microbes are relevant for the severity and progression of cholestatic liver disease. Interestingly, the majority of new drugs that are currently being tested in PBC and PSC in clinical trials act on bile acid homeostasis, where the endobiome is important. In the future, it will be paramount to perform longitudinal studies, through which we can identify new intervention targets, biomarkers or treatment‐stratifiers. In this way, gut microbiome‐based clinical care and therapy may become relevant in cholestatic liver disease within the foreseeable future.     

Gut microbiota dysbiosis in stable coronary artery disease combined with type 2 diabetes mellitus influences cardiovascular prognosis

Background and aimsHost–microbiota interactions involving metabolic pathways have been linked to the pathogenesis of atherosclerotic disease and type 2 diabetes. As stable coronary artery disease (SCAD) patients combined with type 2 diabetes have significantly increased risk for cardiac event, we focused on elucidating the role of microbiota affecting cardiometabolic disease development.Methods and resultsWe used multi-omics analyses (metagenomics and metabolomics) of fecal and serum samples from a prospective cohort including stable coronary artery disease combined with diabetes mellitus (SCAD + T2DM, n = 38), SCAD (n = 71), and healthy control (HC, n = 55). We linked microbiome features to disease severity in a three-pronged association analysis and identified prognostic bacterial biomarkers. We identified that bacterial and metabolic signatures varied significantly between SCAD and SCAD + T2DM groups. SCAD + T2DM individuals were characterized by increased levels of aromatic amino acids and carbohydrates, which correlate with a gut microbiome with enriched biosynthetic potential. Our study also addressed how metformin may confound gut dysbiosis and increase the potential for nitrogen metabolism. In addition, we found that specific bacterial taxa Ruminococcus torques [HR: 2.363 (08–4.56), P = 0.03] was predictive of cardiac survival outcomes.ConclusionOverall, our study identified relationships between features of the gut microbiota (GM) and circulating metabolites, providing a new direction for future studies aiming to understand the host–GM interplay in atherosclerotic cardiovascular pathogenesis.