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.
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.
Abstract
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.
The human gastrointestinal tract is inhabited by various microorganisms, including thousands of bacterial taxa that have yet to be cultured and characterized. In this report, we describe the ...isolation, cultivation, genotypic and phenotypic characterization and taxonomy of five novel anaerobic bacterial strains that were recovered during the massive cultivation and isolation of gut microbes from human faecal samples. On the basis of the polyphasic taxonomic results, we propose two novel genera and five novel species. They are
sp. nov. (type strain NSJ-142
=CGMCC 1.17903
=KCTC 25346
),
sp. nov. (type strain NSJ-176
=CGMCC 1.17933
=KCTC 25355
),
gen. nov. sp. nov. (type strain NSJ-141
=CGMCC 1.17902
=KCTC 25345
),
gen. nov. sp. nov. (type strain NSJ-153
=CGMCC 1.17915
=KCTC 25350
) and
sp. nov. (type strain NSJ-152
=CGMCC 1.17914
=KCTC 25349
).
Non-human primates harbour diverse microbiomes in their guts. As a part of the China Microbiome Initiatives, we cultivated and characterized the gut microbiome of cynomolgus monkeys (
). In this ...report, we communicate the characterization and taxonomy of eight bacterial strains that were obtained from faecal samples of captive cynomolgus monkeys. The results revealed that they represented eight novel bacterial species. The proposed names of the eight novel species are
(type strain MSJ-5
=CGMCC 1.45007
=KCTC 15974
),
MSJd-7
(MSJd-7
=CGMCC 1.45013
=KCTC 25112
),
(MSJ-11
=CGMCC 1.45009
=KCTC 25065
),
(MSJ-4
=CGMCC 1.45006
=KCTC 15975
),
(MSJ-2
=CGMCC 1.32896
=KCTC 15976
),
MSJ-6
(MSJ-6
=CGMCC 1.45008
=KCTC 15973
),
(MSJ-1
=CGMCC 1.31770
=KCTC 15977
) and
(MSJ-40
=CGMCC 1.45012
=KCTC 25071
).
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.
Pericardial effusion (PE) is correlated with outcomes in patients with pulmonary arterial hypertension (PAH). Pulmonary artery denervation (PADN) was used for treatment of PAH. The present study ...aimed to analyze the prognostic value of PE for outcomes after PADN in patients with WHO Group I, Group II and Group IV PAH.
PE, frequently seen in patients with connective tissue disease, was featured by fast heart rate, decreased exercise capacity, more syncope, worsening pulmonary arterial hemodynamic and right atrium size. PADN procedure resulted in dramatic reduction of PE. After a median of 376 days follow-up, the rate of PAH-related event, all-cause death and rehospitalization increased over the PE amount and occurred in 29.8%, 19.7% and 25.2% of patients with PE, different to 3.4%, 3.4% and 6.8% of patients without PE (
= 0.034,
= 0.041 and
= 0.039, respectively). The reduction of PE during follow-up was similar among three groups.
Between March 2012 and July 2014, a total of 66 consecutive patients (52 ± 16 years) who underwent PADN were stratified by no PE (
= 20), PE < 10 mm (
= 29) and PE ≥ 10 mm (
= 17) according to baseline echocardiograph. Dynamic change of PE and its correlation with PAH-related event after PADN were measured.
PE is associated with increased PAH-related event after PADN. PADN results in significant similar reduction of PE among patients with Group I, Group II and Group IV PAH.
Investigate immunoregulation and anti-tumor immunity of FoxP3
Tregs after treatment with rapamycin (RAPA/SRL) plus thymalfasin (Zadaxin) and Huaier extract (PS-T) in a hepatocellular carcinoma (HCC) ...rat model simulating HCC relapse after liver transplant (LT).
We successfully established a rat model simulating HCC relapse after LT using an optimized chemical induction method with TACROLIMUS, methylprednisolone, and diethylnitrosamine as identified by visible liver nodules and hematoxylin-eosin staining. The model rats were then treated with RAPA, Zadaxin, and PS-T. Immune status changes were analyzed by flow cytometry, and protein expression of Akt and mTOR was determined by western blotting. Cytokines were measured by ELISAs.
Combined therapy by RAPA plus Zadaxin and PS-T obviously alleviated hepatic pathological changes and significantly decreased the levels of FoxP3
Tregs in peripheral blood, the spleen, and the liver (P<0.05) and expression of mTOR protein (P<0.01) in the liver, obviously improved survival time (P=0.02). Moreover, the levels of CD8
T cells were increased significantly to almost normal levels (P<0.05) in comparison with no SRL monotherapy protocols. Inhibitory cytokines were also decreased in accordance with FoxP3
Tregs. Significant decreases of IL-10 and TGF-β were observed after SRL-based therapy (P<0.01) in comparison with the other groups. Serum alpha fetoprotein (AFP) and vascular endothelial growth factor (VEGF) levels were also decreased significantly (P<0.05). FoxP3
Tregs showed a negative correlation with CD8
and CD4
/CD8
T cells and a positive correlation with AFP, and VEGF (P<0.05).
SRL-based therapy reduces FoxP3
Tregs to decrease secreted inhibitory cytokines which may enhancement the viability and number of CD8
T cells to exert anti-tumor effects that are mainly mediated through the AKT-mTOR signaling pathway.
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