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result(s) for
"Du, Meng-Xuan"
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Metabolite profiling of human‐originated Lachnospiraceae at the strain level
2022
The human gastrointestinal (GI) tract harbors diverse microbes, and the family Lachnospiraceae is one of the most abundant and widely occurring bacterial groups in the human GI tract. Beneficial and adverse effects of the Lachnospiraceae on host health were reported, but the diversities at species/strain levels as well as their metabolites of Lachnospiraceae have been, so far, not well documented. In the present study, we report on the collection of 77 human‐originated Lachnospiraceae species (please refer hLchsp, https://hgmb.nmdc.cn/subject/lachnospiraceae) and the in vitro metabolite profiles of 110 Lachnospiraceae strains (https://hgmb.nmdc.cn/subject/lachnospiraceae/metabolites). The Lachnospiraceae strains in hLchsp produced 242 metabolites of 17 categories. The larger categories were alcohols (89), ketones (35), pyrazines (29), short (C2–C5), and long (C > 5) chain acids (31), phenols (14), aldehydes (14), and other 30 compounds. Among them, 22 metabolites were aromatic compounds. The well‐known beneficial gut microbial metabolite, butyric acid, was generally produced by many Lachnospiraceae strains, and Agathobacter rectalis strain Lach‐101 and Coprococcus comes strain NSJ‐173 were the top 2 butyric acid producers, as 331.5 and 310.9 mg/L of butyric acids were produced in vitro, respectively. Further analysis of the publicly available cohort‐based volatile‐metabolomic data sets of human feces revealed that over 30% of the prevailing volatile metabolites were covered by Lachnospiraceae metabolites identified in this study. This study provides Lachnospiraceae strain resources together with their metabolic profiles for future studies on host–microbe interactions and developments of novel probiotics or biotherapies. The human‐originated Lachnospiraceae biobank included 77 species was constructed. In vitro metabolite profiling of 110 Lachnospiraceae strains yielded 242 metabolites of 17 categories. Many Lachnospiraceae strains produce short‐chain fatty acids, and Agathobacter rectalis strain Lach‐101 and Coprococcus comes strain NSJ‐173 are the top two butyric acid producers in vitro. Highlights The human‐originated Lachnospiraceae biobank included 77 species was constructed. In vitro metabolite profiling of 110 Lachnospiraceae strains yielded 242 metabolites of 17 categories. Many Lachnospiraceae strains produce SCFAs, and Agathobacter rectalis strain Lach‐101 and Coprococcus comes strain NSJ‐173 are the top two butyric acid producers in vitro.
Journal Article
The Mouse Gut Microbial Biobank expands the coverage of cultured bacteria
2020
Mice are widely used as experimental models for gut microbiome (GM) studies, yet the majority of mouse GM members remain uncharacterized. Here, we report the construction of a mouse gut microbial biobank (mGMB) that contains 126 species, represented by 244 strains that have been deposited in the China General Microorganism Culture Collection. We sequence and phenotypically characterize 77 potential new species and propose their nomenclatures. The mGMB includes 22 and 17 species that are significantly enriched in ob/ob and wild-type C57BL/6J mouse cecal samples, respectively. The genomes of the 126 species in the mGMB cover 52% of the metagenomic nonredundant gene catalog (sequence identity ≥ 60%) and represent 93–95% of the KEGG-Orthology-annotated functions of the sampled mouse GMs. The microbial and genome data assembled in the mGMB enlarges the taxonomic characterization of mouse GMs and represents a useful resource for studies of host-microbe interactions and of GM functions associated with host health and diseases.
Here, the authors established and characterized the mouse gut microbial biobank (mGMB), which includes 244 strains and 126 species that enlarges previous mouse intestinal bacterial collections and represents a resource for studies using mouse models to investigate microbiome-associated health and disease.
Journal Article
Enlightening the taxonomy darkness of human gut microbiomes with a cultured biobank
2021
Background
In gut microbiome studies, the cultured gut microbial resource plays essential roles, such as helping to unravel gut microbial functions and host-microbe interactions. Although several major studies have been performed to elucidate the cultured human gut microbiota, up to 70% of the Unified Human Gastrointestinal Genome species have not been cultured to date. Large-scale gut microbial isolation and identification as well as availability to the public are imperative for gut microbial studies and further characterizing human gut microbial functions.
Results
In this study, we constructed a human Gut Microbial Biobank (hGMB; homepage:
hgmb.nmdc.cn
) through the cultivation of 10,558 isolates from 31 sample mixtures of 239 fresh fecal samples from healthy Chinese volunteers, and deposited 1170 strains representing 400 different species in culture collections of the International Depository Authority for long-term preservation and public access worldwide. Following the rules of the International Code of Nomenclature of Prokaryotes, 102 new species were characterized and denominated, while 28 new genera and 3 new families were proposed. hGMB represented over 80% of the common and dominant human gut microbial genera and species characterized from global human gut 16S rRNA gene amplicon data (
n
= 11,647) and cultured 24 “most-wanted” and “medium priority” taxa proposed by the Human Microbiome Project. We in total sequenced 115 genomes representing 102 novel taxa and 13 previously known species. Further in silico analysis revealed that the newly sequenced hGMB genomes represented 22 previously uncultured species in the Unified Human Gastrointestinal Genome (UHGG) and contributed 24 representatives of potentially “dark taxa” that had not been discovered by UHGG. The nonredundant gene catalogs generated from the hGMB genomes covered over 50% of the functionally known genes (KEGG orthologs) in the largest global human gut gene catalogs and approximately 10% of the “most wanted” functionally unknown proteins in the FUnkFams database.
Conclusions
A publicly accessible human Gut Microbial Biobank (hGMB) was established that contained 1170 strains and represents 400 human gut microbial species. hGMB expands the gut microbial resources and genomic repository by adding 102 novel species, 28 new genera, 3 new families, and 115 new genomes of human gut microbes.
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Video abstract
Journal Article
Gut commensal Christensenella minuta modulates host metabolism via acylated secondary bile acids
2024
A strong correlation between gut microbes and host health has been observed in numerous gut metagenomic cohort studies. However, the underlying mechanisms governing host–microbe interactions in the gut remain largely unknown. Here we report that the gut commensal
Christensenella minuta
modulates host metabolism by generating a previously undescribed class of secondary bile acids with 3-O-acylation substitution that inhibit the intestinal farnesoid X receptor. Administration of
C. minuta
alleviated features of metabolic disease in high fat diet-induced obese mice associated with a significant increase in these acylated bile acids, which we refer to as 3-O-acyl-cholic acids. Specific knockout of intestinal farnesoid X receptor in mice counteracted the beneficial effects observed in their wild-type counterparts. Finally, we showed that 3-O-acyl-CAs were prevalent in healthy humans but significantly depleted in patients with type 2 diabetes. Our findings indicate a role for
C. minuta
and acylated bile acids in metabolic diseases.
The gut commensal
Christensenalla minuta
produces a previously undescribed class of secondary bile acids that counteract features of metabolic disease and are depleted in patients with type 2 diabetes.
Journal Article
Alkaliphilus flagellata sp. nov., Butyricicoccus intestinisimiae sp. nov., Clostridium mobile sp. nov., Clostridium simiarum sp. nov., Dysosmobacter acutus sp. nov., Paenibacillus brevis sp. nov., Peptoniphilus ovalis sp. nov., and Tissierella simiarum sp. nov., isolated from monkey feces
2021
Non-human primates harbor diverse microbiomes in their guts. As a part of China Microbiome Initiatives, we cultivated and characterized the gut microbiome of cynomolgus monkeys (Macaca fascicularis). In this report, we communicate the characterization and taxonomy of 8 bacterial strains that were obtained from fecal samples of captive cynomolgus monkeys. The results revealed that they represented 8 novel bacterial species. The proposed names of the 8 novel species are Alkaliphilus flagellate (type strain MSJ-5T =CGMCC 1.45007T=KCTC 15974T), Butyricicoccus intestinisimiae MSJd-7T (type strain MSJd-7T =CGMCC 1.45013T =KCTC 25112T), Clostridium mobile (type strain MSJ-11T =CGMCC 1.45009T=KCTC 25065T), Clostridium simiarum (type strain MSJ-4T =CGMCC 1.45006T =KCTC 15975T), Dysosmobacter acutus (type strain MSJ-2T =CGMCC 1.32896T=KCTC 15976T), Paenibacillus brevis MSJ-6T (type strain MSJ-6T =CGMCC 1.45008T=KCTC 15973T), Peptoniphilus ovalis (type strain MSJ-1T =CGMCC 1.31770T=KCTC 15977T), and Tissierella simiarum (type strain MSJ-40T =CGMCC 1.45012T=KCTC 25071T). Competing Interest Statement The authors have declared no competing interest.
Energy Metabolism Enhance Perylenequinone Biosynthesis in Shiraia sp. Slf14 through Promoting Mitochondrial ROS Accumulation
2024
Perylenequinones (PQs) are important natural compounds that have been extensively utilized in recent years as agents for antimicrobial, anticancer, and antiviral photodynamic therapies. In this study, we investigated the molecular mechanisms regulating PQ biosynthesis by comparing Shiraia sp. Slf14 with its low PQ titer mutant, Slf14(w). The results indicated that the strain Slf14 exhibited a higher PQ yield, a more vigorous energy metabolism, and a more pronounced oxidation state compared to Slf14(w). Transcriptome analysis consistently revealed that the differences in gene expression between Slf14 and Slf14(w) are primarily associated with genes involved in redox processes and energy metabolism. Additionally, reactive oxygen species (ROS) were shown to play a crucial role in promoting PQ synthesis, as evidenced by the application of ROS-related inhibitors and promoters. Further results demonstrated that mitochondria are significant sources of ROS, which effectively regulate PQ biosynthesis in Shiraia sp. Slf14. In summary, this research revealed a noteworthy finding: the higher energy metabolism of the strain Slf14 is associated with increased intracellular ROS accumulation, which in turn triggers the activation and expression of gene clusters responsible for PQ synthesis.
Journal Article
Sirolimus treatment for cirrhosis or hepatocellular carcinoma patients accompanied by psoriasis after liver transplantation: A single center experience
by
Pan, Li-Chao
,
Zheng, Yong-Gen
,
Yang, Shao-Zhen
in
Complications and side effects
,
Cytokines
,
Development and progression
2017
There is currently no consensus on the most suitable therapeutic approach for psoriasis (PS) co-existing with posthepatic cirrhosis (PCs) and hepatocellular carcinoma (HCC) following liver transplantation (LT). The present study provides an analysis of the therapeutic experience of such patients. Five LT recipients (two with PC and three with HCC) with accompanying PS were included. The induction program consisted of methylprednisolone plus basiliximab treatment. The initial postoperative treatment scheme consisted of tacrolimus (FK506) plus mycophenolate mofetil (MMF) and hormone; the latter was withdrawn 1 week after LT. The patients with PC had been using FK506 with or without a postoperative MMF program; the patients with HCC and recurrence of PS had been switched to a sirolimus (SRL)-based replacement therapy. Furthermore, all patients received anti-hepatitis B virus (HBV) therapy. The patients were followed up after 8.3±1.5 years. There was a positive correlation between HBV-DNA copy numbers, and psoriatic area and severity index (PASI) scores (r=0.97; P=0.006). The PASI scores were decreased significantly at 6 months following surgery compared with pre-transplantation (P<0.05). The patients who had received the FK506-based treatment experienced PS recurrence two years post-transplantation. The PASI scores increased significantly (P<0.05) and then declined gradually, maintaining a stable level (P<0.05) by 1 year after switching to the SRL-based treatment. The patients who had received the SRL-based treatment exhibited no recurrence of PS. The results of the present study suggest that SRL therapy provides a promising novel treatment method for patients with PS following LT that may be superior to tacrolimus treatment. When co-existing HBV is present pre-transplantation, regular injection of human hepatitis B immunoglobulin should be used to prevent the HBV from relapsing or aggravating the PS.
Journal Article
Synthesis and bioassay of β-(1,4)-D-mannans as potential agents against Alzheimer's disease
by
Ru-wei JIANG Xiao-guang DU Xuan ZHANG Xin WANG Ding-yu HU Tao MENG Yue-lei CHEN Mei-yu GENG Jing-kang SHEN
in
SH-SY5Y
,
甘露聚糖
,
生物测定
2013
Aim: Oligomannurarate 971 derived from a marine plant has shown neuroprotective effects. In this study we synthesized a series of truncated derivatives of the oligosaccharide, and investigated the effect of these derivatives against Aβ peptide toxicity in vitro. Methods: The sulfoxide method was applied to synthesize the derivatives. SH-SY5Y human neuroblastoma cells were treated with Aβ1-40 (2 pmol/L), and the cell viability was detected using a CCK8 assay. Results: A series of β-(1,4)-D-mannosyl oligosaccharide, ranging from the disaccharide to the hexasaccharide, were synthesized. Addition of 10 pmol/L β-(1,4)-D-mannobiose 6, β-(1,4)-D-mannotriose 9 or β-(1,4)-D-mannotetraose 12 in SH-SY5Y cells significantly attenuated Aβ1-40-induced toxicity. The efficacies were similar to those caused by 10 pmol/L oligomannurarate 971 or alzhemed. Other oligosaccharides including oligomaltoses and oligocelluloses were less active. Conclusion: Synthetic homogeneous short chain β-(1,4)-D-mannans shows neuroprotective effect against Aβ peptide toxicity similar to that of heterogeneous oligomannurarate 971 and alzhemed.
Journal Article