[Distribution characteristics of trimethylamine N-oxide and its association with gut microbiota].

OBJECTIVE: To analyze the distribution of trimethylamine N-oxide (TMAO) in healthy adults with different risk factors and explore its association with gut microbiota. METHODS: We collected fasting blood samples and fresh fecal samples from 181 subjects without atherogenesis in the carotid arteries. Plasma TMAO levels of the subjects were determined using stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS). The fecal DNA was extracted, and the 16S rRNA V4 tags were amplified and sequenced by Illumina HiSeq 2000. The association between TMAO and classical cardiovascular risk factors were analyzed. Gut microbial community structure was analyzed with QIIME, and LEfSe was used to identify the biomarkers. RESULTS: The median (IQR) TMAO level was 2.66 (1.96-4.91) µmol/L in the subjects. TMAO level was significantly correlated with body mass index and operational taxonomic units (OTU). Individuals with high TMAO levels were found to have abundant Clostridiales, Phascolarctobacterium, Oscillibacter, and Alistipes but less abundant Anaerosprobacter. CONCLUSION: Chinese subjects have in general low levels of TMAO. TMAO levels are not significantly correlated with the classical cardiovascular risk factors or the gut microbial structures.

Dysbiosis of Gut Microbiota With Reduced Trimethylamine-N-Oxide Level in Patients With Large-Artery Atherosclerotic Stroke or Transient Ischemic Attack.

BACKGROUND: Gut microbiota has been suggested to play a role in almost all major diseases including cardio- and cerebrovascular diseases. A possible mechanism is the transformation of dietary choline and l-carnitine into trimethylamine by gut bacteria. This metabolite is further oxidized into trimethylamine-N-oxide (TMAO) in liver and promotes atherogenesis. Nevertheless, little is known about gut microbial diversity and blood TMAO levels in stroke patients. METHODS AND RESULTS: We performed a case-control study of patients with large-artery atherosclerotic ischemic stroke and transient ischemic attack. TMAO was determined with liquid chromatography tandem mass spectrometry. Gut microbiome was profiled using Illumina sequencing of the 16S rRNA V4 tag. Within the asymptomatic control group, participants with and without carotid atherosclerotic plaques showed similar levels of TMAO without a significant difference in gut microbiota; however, the gut microbiome of stroke and transient ischemic attack patients was clearly different from that of the asymptomatic group. Stroke and transient ischemic attack patients had more opportunistic pathogens, such as Enterobacter, Megasphaera, Oscillibacter, and Desulfovibrio, and fewer commensal or beneficial genera including Bacteroides, Prevotella, and Faecalibacterium. This dysbiosis was correlated with the severity of the disease. The TMAO level in the stroke and transient ischemic attack patients was significantly lower, rather than higher, than that of the asymptomatic group. CONCLUSIONS: Participants with asymptomatic atherosclerosis did not exhibit an obvious change in gut microbiota and blood TMAO levels; however, stroke and transient ischemic attack patients showed significant dysbiosis of the gut microbiota, and their blood TMAO levels were decreased.

Different Dynamic Patterns of ß-Lactams, Quinolones, Glycopeptides and Macrolides on Mouse Gut Microbial Diversity.

The adverse impact of antibiotics on the gut microbiota has attracted extensive interest, particularly due to the development of microbiome research techniques in recent years. However, a direct comparison of the dynamic effects of various types of antibiotics using the same animal model has not been available. In the present study, we selected six antibiotics from four categories with the broadest clinical usage, namely, ß-lactams (Ceftriaxone Sodium, Cefoperazone/Sulbactam and meropenem), quinolones (ofloxacin), glycopeptides (vancomycin), and macrolides (azithromycin), to treat BALB/c mice. Stool samples were collected during and after the administration of antibiotics, and microbial diversity was analyzed through Illumina sequencing and bioinformatics analyses using QIIME. Both α and ß diversity analyses showed that ceftriaxone sodium, cefoperazone/sulbactam, meropenem and vancomycin changed the gut microbiota dramatically by the second day of antibiotic administration whereas the influence of ofloxacin was trivial. Azithromycin clearly changed the gut microbiota but much less than vancomycin and the ß-lactams. In general, the community changes induced by the three ß-lactam antibiotics showed consistency in inhibiting Papillibacter, Prevotella and Alistipes while inducing massive growth of Clostridium. The low diversity and high Clostridium level might be an important cause of Clostridium difficile infection after usage of ß-lactams. Vancomycin was unique in that it inhibited Firmicutes, mainly the genus Clostridium. On the other hand, it induced the growth of Escherichia and effect lasted for months afterward. Azithromycin and meropenem induced the growth of Enterococcus. These findings will be useful for understanding the potential adverse effects of antibiotics on the gut microbiome and ensuring their better usage.