Longitudinal Multi-omic Phenotyping Reveals Host-microbe Responses to Bariatric Surgery, Glycaemic Control and Obesity

Resolution of type-2 diabetes (T2D) is common following bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB). However, the underlying mechanisms have not been fully elucidated. To address this we compared the integrated serum, urine and faecal metabolic profiles of obese participants with and without T2D (n=81, T2D=42) with participants who underwent RYGB or sleeve gastrectomy (pre and 3-months post-surgery; n=27), taking diet into account. We co-modelled these data with shotgun metagenomic profiles of the gut microbiota to provide a comprehensive atlas of host-gut microbe responses to bariatric surgery, weight-loss and glycaemic control at the systems level. Bariatric surgery reversed a number of disrupted pathways characteristic of T2D. The differential metabolite set representative of bariatric surgery overlapped with both diabetes (19.3% commonality) and BMI (18.6% commonality). However, the percentage overlap between diabetes and BMI was minimal (4.0% commonality), consistent with weight-independent mechanisms of T2D resolution. The gut microbiota was more strongly correlated to BMI than T2D, although we identified some pathways such as amino acid metabolism that correlated with changes to the gut microbiota and which influence glycaemic control. Improved understanding of GM-host co-metabolism may lead to novel therapies for weight-loss or diabetes.

The gut microbiome and hepatocellular carcinoma: Implications for early diagnostic biomarkers and novel therapies

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. HCC almost exclusively develops in patients with chronic liver disease, driven by a vicious cycle of liver injury, inflammation and regeneration that typically spans decades. Recently, increasing investigation of the microbiome–gut–liver axis enhances our understanding of the role of the gut microbiota in promoting the progression of liver disease and the development of HCC. In this review, we summarize mechanisms by which the gut microbiota promotes hepatocarcinogenesis, focusing on bacterial dysbiosis, the leaky gut, microbe-associated molecular patterns and bacterial metabolites as key pathways that drive cancer-promoting liver inflammation, fibrosis and genotoxicity. Furthermore, we discuss the important potential of gut microbiota as an early diagnostic biomarker of HCC. Gut microbiota may be as a promising target for the simultaneous prevention of chronic liver disease progression and HCC development in patients with advanced liver disease. We outlook in detail therapeutic modalities in which targeting the gut microbiota for the prevention of disease progression and HCC development seems promising.

Biosynthesis-Guided Discovery of Enteropeptins, Unusual Sactipeptides Containing an N-Methylornithine

The combination of next-generation DNA sequencing technologies and bioinformatics have revitalized natural product discovery. Using a new bioinformatic search strategy, we recently identified ~600 gene clusters in animal microbiomes that code for ribosomal peptide natural products synthesized by radical S-adenosylmethionine enzymes. These grouped into 16 subfamilies and pointed to an unexplored microbiome biosynthetic landscape. Herein, we report the structure, biosynthesis, and function of one of these natural product groups, that we term enteropeptins, from the gut microbe Enterococcus cecorum. We elucidate three novel reactions, each catalyzed by a different family of metalloenzymes, in the biosynthesis of enteropeptins. Among these, we characterize the founding member of a widespread superfamily of Fe-S-containing methyltransferases, which, together with a di-Mn-dependent arginase, installs an N-methylornithine in the peptide sequence. Biological assays with the mature product revealed bacteriostatic activity only against the producing strain, extending an emerging theme of fratricidal or self-inhibitory metabolites in microbiome firmicutes.

Citrus reticulatae pericarpium Extract Decreases the Susceptibility to HFD-Induced Glycolipid Metabolism Disorder in Mice Exposed to Azithromycin in Early Life

BackgroundStudies have shown that gut microbe disorder in mice due to early-life antibiotic exposure promotes glycolipid metabolism disorder in adulthood. However, the underlying mechanism remains unclear and there is not yet an effective intervention or treatment for this process.PurposeThe study investigated whether early-life azithromycin (AZT) exposure in mice could promote high-fat diet (HFD)-induced glycolipid metabolism disorder in adulthood. Moreover, the effect of citrus reticulata pericarpium (CRP) extract on glycolipid metabolism disorder via regulation of gut microbiome in mice exposed to antibodies early in life were investigated.Methods and ResultsThree-week-old mice were treated with AZT (50 mg/kg/day) via drinking water for two weeks and then were fed a CRP diet (1% CRP extract) for four weeks and an HFD for five weeks. The results showed that early-life AZT exposure promoted HFD-induced glycolipid metabolism disorder, increased the levels of inflammatory factors, promoted the flora metabolism product trimethylamine N-oxide (TMAO), and induced microbial disorder in adult mice. Importantly, CRP extract mitigated these effects.ConclusionTaken together, these findings suggest that early-life AZT exposure increases the susceptibility to HFD-induced glycolipid metabolism disorder in adult mice, and CRP extract can decrease this susceptibility by regulating gut microbiome.

Understanding the Functional Activity of Polyphenols Using Omics-Based Approaches

Plant polyphenols are the main category of natural active substances, and are distributed widely in vegetables, fruits, and plant-based processed foods. Polyphenols have a beneficial performance in preventing diseases and maintaining body health. However, its action mechanism has not been well understood. Foodomics is a novel method to sequence and widely used in nutrition, combining genomics, proteomics, transcriptomics, microbiome, and metabolomics. Based on multi-omics technologies, foodomics provides abundant data to study functional activities of polyphenols. In this paper, physiological functions of various polyphenols based on foodomics and microbiome was discussed, especially the anti-inflammatory and anti-tumor activities and gut microbe regulation. In conclusion, omics (including microbiomics) is a useful approach to explore the bioactive activities of polyphenols in the nutrition and health of human and animals.

Changes in Trimethylamine-N-oxide Levels in Obese Patients following Laparoscopic Roux-en-Y Gastric Bypass or Sleeve Gastrectomy in a Korean Obesity Surgical Treatment Study (KOBESS)

Trimethylamine N-oxide (TMAO), a gut microbe-dependent metabolite, has been implicated as a novel risk factor for cardiovascular events related to obesity and type 2 diabetes mellitus (T2DM). The aim of the study was to test the hypothesis if TMAO is associated with the reduction of cardiovascular disease in the Korean obese patients who underwent bariatric surgery. From a subgroup of a multicenter, nonrandomized, controlled trial, titled KOBESS, 38 obese patients, 18 with and 20 without T2DM, who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were investigated. Bariatric surgery is indicated for Korean patients with a body mass index (BMI) ≥ 35 kg/m2 or for Korean patients with a BMI ≥ 30 kg/m2 who have comorbidities. Serum levels of TMAO and its precursors, betaine, carnitine, and choline were measured before and six months after bariatric surgery. The levels of TMAO and its precursors did not differ between obese patients with T2DM and non-T2DM at baseline. However, TMAO increased more than twofold in patients with T2DM after RYGB surgery, but not in patients without T2DM. Choline levels were decreased by half in all patients after RYGB. In patients with T2DM who underwent SG, TMAO, betaine, and carnitine levels did not change after the surgery. Furthermore, in obese patients who underwent bariatric surgery, increased TMAO levels were associated with both T2DM and RYGB, while reduced choline levels were associated with RYGB. These associations need to be further elucidated in follow-up studies to gain further insights into the relationship between TMAO levels and bariatric surgery outcomes.

The Potential Role of Vitamin B12 in the Prevention of COVID-19 Complications: A Narrative Review

The elderly are more prone to mortality from COVID-19 infection, as they are susceptible to develop acute respiratory distress syndrome (ARDS). For COVID-19 patients with ARDS caused by sepsis or septic shock, high-dose parenteral vitamin B12 appears to be a potential new treatment option. Vitamin B12 may play a substantial impact in COVID-19 morbidity and mortality reduction owing to its function in DNA synthesis, cellular control, improvement of anti-inflammatory immune responses, and decrease of pro-inflammatory responses. This review aims to assess the functional role of Vitamin B12 in COVID-19 in terms of its immunomodulatory effect, role in cellular and humoral immunity and maintaining the gut microbe homeostasis. From data inception to June 2021, accessible electronic databases were searched for research/review articles reporting on the function of Vitamin B12 in COVID-19. Scopus, Web of Science, PubMed, WHO worldwide research on COVID-19 and the clinical trials registration “https://clinicaltrials.gov/” were used to conduct the systematic search by using keywords: “COVID-19 and “Vitamin B12”. Also, based on these outcomes, it can be concluded that Vitamin B12 may have a potential role in preventing COVID-19 complications. Further, studies evaluating the role of Vitamin B12 in COVID-19 may open a new array of ideas on the optimal and the well-tolerated dose and timing of its administration in COVID-19 patients.

Network of Interactions Between Gut Microbiome, Host Biomarkers, and Urine Metabolome in Carotid Atherosclerosis

Comprehensive analyses of multi-omics data may provide insights into interactions between different biological layers concerning distinct clinical features. We integrated data on the gut microbiota, blood parameters and urine metabolites of treatment-naive individuals presenting a wide range of metabolic disease phenotypes to delineate clinically meaningful associations. Trans-omics correlation networks revealed that candidate gut microbial biomarkers and urine metabolite feature were covaried with distinct clinical phenotypes. Integration of the gut microbiome, the urine metabolome and the phenome revealed that variations in one of these three systems correlated with changes in the other two. In a specific note about clinical parameters of liver function, we identified Eubacteriumeligens, Faecalibacteriumprausnitzii and Ruminococcuslactaris to be associated with a healthy liver function, whereas Clostridium bolteae, Tyzzerellanexills, Ruminococcusgnavus, Blautiahansenii, and Atopobiumparvulum were associated with blood biomarkers for liver diseases. Variations in these microbiota features paralleled changes in specific urine metabolites. Network modeling yielded two core clusters including one large gut microbe-urine metabolite close-knit cluster and one triangular cluster composed of a gut microbe-blood-urine network, demonstrating close inter-system crosstalk especially between the gut microbiome and the urine metabolome. Distinct clinical phenotypes are manifested in both the gut microbiome and the urine metabolome, and inter-domain connectivity takes the form of high-dimensional networks. Such networks may further our understanding of complex biological systems, and may provide a basis for identifying biomarkers for diseases. Deciphering the complexity of human physiology and disease requires a holistic and trans-omics approach integrating multi-layer data sets, including the gut microbiome and profiles of biological fluids. By studying the gut microbiome on carotid atherosclerosis, we identified microbial features associated with clinical parameters, and we observed that groups of urine metabolites correlated with groups of clinical parameters. Combining the three data sets, we revealed correlations of entities across the three systems, suggesting that physiological changes are reflected in each of the omics. Our findings provided insights into the interactive network between the gut microbiome, blood clinical parameters and the urine metabolome concerning physiological variations, and showed the promise of trans-omics study for biomarker discovery.