An expanding body of research indicates a correlation between the gut microbiota and various diseases. Metabolites produced by the gut microbiota act as mediators between the gut microbiota and the host, interacting with multiple systems in the human body to regulate physiological or pathological functions. However, further investigation is still required to elucidate the underlying mechanisms. One such metabolite involved in choline metabolism by gut microbes is trimethylamine (TMA), which can traverse the intestinal epithelial barrier and enter the bloodstream, ultimately reaching the liver where it undergoes oxidation catalyzed by flavin-containing monooxygenase 3 (FMO3) to form trimethylamine N-oxide (TMAO). While some TMAO is eliminated through renal excretion, remaining amounts circulate in the bloodstream, leading to systemic inflammation, endoplasmic reticulum (ER) stress, mitochondrial stress, and disruption of normal physiological functions in humans. As a representative microbial metabolite originating from the gut, TMAO has significant potential both as a biomarker for monitoring disease occurrence and progression and for tailoring personalized treatment strategies for patients. This review provides an extensive overview of TMAO sources and its metabolism in human blood, as well as its impact on several major human diseases. Additionally, we explore the latest research areas related to TMAO along with future directions.

Ferredoxin 1 (FDX1) functions by transferring electrons from NADPH to mitochondrial cytochrome P450 via the ferredoxin reductase and is the key regulator in copper-dependent cell death. Although mounting evidence supports a vital role for FDX1 in tumorigenesis of some cancers, no pan-cancer analysis of FDX1 has been reported. Therefore, we aimed to explore the prognostic value of FDX1 in pan-cancer and investigate its potential immune function. Based on data from The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, Human Protein Atlas, and Gene Set Cancer Analysis, we used a range of bioinformatics approaches to explore the potential carcinogenic role of FDX1, including analyzing the relationship between FDX1 expression and prognosis, DNA methylation, RNA methylation-related genes, mismatch repair (MMR) gene, microsatellite instability (MSI), tumor mutation burden (TMB), tumor microenvironment (TME), immune-related genes, and drug sensitivity in different tumors. The results show that FDX1 was lowly expressed in most cancers but higher in glioblastoma multiforme, stomach adenocarcinoma, and uterine corpus endometrial carcinoma. Moreover, FDX1 expression was positively or negatively associated with prognosis in different cancers. FDX1 expression was significantly associated with DNA methylation in 6 cancers, while there was a correlation between FDX1 expression and RNA methylation-related genes and MMR gene in most cancers. Furthermore, FDX1 expression was significantly associated with MSI in 8 cancers and TMB in 10 cancers. In addition, FDX1 expression was also significantly correlated with immune cell infiltration, immune-related genes, TME, and drug resistance in various cancers. An experiment in vitro showed FDX1 is downregulated by elesclomol, resulting in inhibiting cell viability of bladder cancer, clear cell renal cell carcinoma, and prostate cancer cells. Our study reveals that FDX1 can serve as a potential therapeutic target and prognostic marker for various malignancies due to its vital role in tumorigenesis and tumor immunity.

An increasing number of studies have shown that the consumption of soybeans and soybeans products is beneficial to human health, and the biological activity of soy products may be attributed to the presence of Soy Isoflavones (SI) in soybeans. In the intestinal tracts of humans and animals, certain specific bacteria can metabolize soy isoflavones into equol. Equol has a similar chemical structure to endogenous estradiol in the human body, which can bind with estrogen receptors and exert weak estrogen effects. Therefore, equol plays an important role in the occurrence and development of a variety of hormone-dependent malignancies such as breast cancer and prostate cancer. Despite the numerous health benefits of equol for humans, only 30-50% of the population can metabolize soy isoflavones into equol, with individual variation in gut microbiota being the main reason. This article provides an overview of the relevant gut microbiota involved in the synthesis of equol and its anti-tumor effects in various types of cancer. It also summarizes the molecular mechanisms underlying its anti-tumor properties, aiming to provide a more reliable theoretical basis for the rational utilization of equol in the field of cancer treatment.

Alterations in the microbiome of the gut and oral cavity are involved in the etiopathogenesis of systemic lupus erythematosus (SLE). We aimed to assess whether both microbiome compositions in feces and saliva were specific in patients with SLE. A total of 35 patients with SLE, as well as sex- and age-matched asymptomatic subjects as healthy control (HC) group were recruited. Fecal swabs and saliva samples were collected from the participants. 16S ribosomal RNA gene sequencing was performed on the samples. Compared with the HC group, reduced bacterial richness and diversity were detected in the feces of patients with SLE, and increased bacterial diversity in their saliva. Both feces and saliva samples explained the cohort variation. The feces were characterized by enrichment of Lactobacillus, and depletion of an unclassified bacterium in the Ruminococcaceae family and Bifidobacterium. Lack of Bifidobacterium was observed in patients with arthritis. Akkermansia and Ruminococcus negatively correlated with the serum levels of C3. In saliva, Veillonella, Streptococcus, and Prevotella were dominant, and Bacteroides was negatively associated with disease activity. These findings can assist us to comprehensively understand the bacterial profiles of different body niches in SLE patients.

Background: Kidney stone disease (KSD) is more common in individuals with hypertension (HTN) than in individuals with normotension (NTN). Urinary dysbiosis is associated with urinary tract disease and systemic diseases. However, the role of the urinary microbiome in KSD complicated with HTN remains unclear. Methods: This study investigated the relationship between the pelvis urinary microbiome and blood pressure (BP) in patients with KSD co-occurring with HTN (KSD-HTN) and healthy controls (HC) by conducting 16S rRNA gene sequencing of bacteria in urine samples. The urine samples were collected (after bladder disinfection) from 50 patients with unilateral kidney calcium stones and NTN (n = 12), prehypertension (pHTN; n = 11), or HTN (n = 27), along with 12 HCs. Results: Principal coordinates analysis showed that there were significant differences in the urinary microbiomes not only between KSD patients and HCs but also between KSD-pHTN or KSD-HTN patients and KSD-NTN patients. Gardnerella dominated in HCs, Staphylococcus dominated in KSD-NTN patients and Sphingomonas dominated in both KSD-pHTN and KSD-HTN patients. The abundance of several genera including Acidovorax, Gardnerella and Lactobacillus was correlated with BP. Adherens junction and nitrogen and nucleotide metabolism pathways, among others, were associated with changes in BP. Conclusions: The findings suggest that patients with KSD complicated with HTN have a unique urinary microbiome profile and that changes in the microbiome may reflect disease progression and may be useful to monitor response to treatments.