Shotgun metagenomics reveals both taxonomic and tryptophan pathway differences of gut microbiota in major depressive disorder patients.

BACKGROUND: The microbiota-gut-brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients. METHODS: We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD. RESULTS: The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890. CONCLUSIONS: The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.

Shotgun metagenomics reveals both taxonomic and tryptophan pathway differences of gut microbiota in bipolar disorder with current major depressive episode patients.

BACKGROUND: The microbiome-gut-brain axis, especially the microbial tryptophan biosynthesis and metabolism pathway (MiTBamp), is closely connected to bipolar disorder with current major depressive episode (BPD). METHODS: We performed shotgun metagenomics sequencing (SMS) of faecal samples from 25 BPD patients and 28 healthy controls (HCs). Except for the microbiota taxa and MiTBamp analyses, we also built a classification model using the Random Forests (RF) and Boruta algorithm to find the microbial biomarkers for BPD. RESULTS: Compared to HCs, the phylum Bacteroidetes abundance was significantly reduced, whereas that of the Actinobacteria and Firmicutes were significantly increased in BPD patients. We also identified 38 species increased and 6 species decreased significantly in the BPD group. In the MiTBamp, we identified that two Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K00658 and K00837) were significantly lower in the BPD, and five KOs (K01696, K00382, K00626, K01667, and K03781) were significantly higher in the BPD group. We also identified significant genera and species which were closely related to these KOs. Finally, RF classification based on gut microbiota at the genus level can achieve an area under the receiver operating characteristic curve of 0.997. LIMITATIONS: The features of cross-sectional design, limited sample size, the heterogeneity of bipolar disorders, and a lack of serum/plasma tryptophan concentration measurements. CONCLUSIONS: The present findings enable a better understanding of changes in gastrointestinal microbiome and MiTBamp in BPD. Alterations of microbes may have potential as biomarkers for distinguishing the BPD patients form HCs.

Similarly in depression, nuances of gut microbiota: Evidences from a shotgun metagenomics sequencing study on major depressive disorder versus bipolar disorder with current major depressive episode patients.

BACKGROUND: To probe the differences of gut microbiota among major depressive disorder (MDD), bipolar disorder with current major depressive episode (BPD) and health participants. METHODS: Thirty one MDD patients, thirty BPD patients, and thirty healthy controls (HCs) were recruited. All the faecal samples were analyzed by shotgun metagenomics sequencing. Except for routine analyses of alpha diversity, we specially designed a new indicator, the Gm coefficient, to evaluate the inequality of relative abundances of microbiota for each participant. RESULTS: The Gm coefficients are significant decreased in both MDD and BPD groups. The relative abundances of increased phyla Firmicutes and Actinobacteria and decreased Bacteroidetes were significantly in the MDD and BPD groups. At genus level, four of top five enriched genera (Bacteroides, Clostridium, Bifidobacterium, Oscillibacter and Streptococcus) were found increased significantly in the MDD and BPD groups compared with HCs. The genera Escherichia and Klebsiella showed significant changes in abundances only between the BPD and HC groups. At the species level, compared with BPD patients, MDD patients had a higher abundance of Prevotellaceae including Prevotella denticola F0289, Prevotella intermedia 17, Prevotella ruminicola, and Prevotella intermedia. Furthermore, the abundance of Fusobacteriaceae, Escherichia blattae DSM 4481 and Klebsiella oxytoca were significantly increased, whereas the Bifidobacterium longum subsp. infantis ATCC 15697 = JCM 1222 was significantly reduced in BPD group compared with MDD group. CONCLUSIONS: Our study suggested that gut microbiota may be involved in the pathogenesis of both MDD and BPD patients, and the nuances of bacteria may have the potentiality of being the biomarkers of MDD and BPD.

Upregulation of Circulating miR-195-3p in Heart Failure.

OBJECTIVES: Many circulating microRNAs (miRs) have been shown to have potential biomarker effects in cardiovascular disease. We studied the dysregulation of circulating miR-195-3p in patients with heart failure (HF) to elucidate its value as a potential biomarker for HF. METHODS: Eight ischemic HF (IHF) patients, 8 nonischemic HF patients (NIHF), and 8 healthy volunteers (matched by age and sex - normal controls [NCs]) were chosen for miR sequencing. The plasma RNA was extracted, and a small RNA library of HF was established and then sequenced using next-generation sequencing (NGS) technology. The miR-195-3p was selected for a second clinical study in 60 IHF, 48 NIHF patients, and 35 NCs for qRT-PCR validation. RESULTS: The expression of circulating miR-195-3p in the IHF group was increased 69.5-fold compared with the NC group using NGS technique, and it was the most elevated in all upregulated miRs. MiR-195-3p was ranked in the top 1 of all upregulated miRs in contribution to HF based on a random forest model analysis. The upregulation of circulating miR-195-3p was also validated with the qRT-PCR method, and receiver operating characteristic curve analysis showed that the area under the curve (AUC) was 0.831. CONCLUSIONS: The circulating miR-195-3p was upregulated in IHF and NIHF patients and could be a potential biomarker for HF.