A single bacterium restores the microbiome dysbiosis to protect bones from destruction in a rat model of rheumatoid arthritis

Pan, Hudan; Guo, Ruijin; Ju, Yanmei; Wang, Qi; Zhu, Jun; Xie, Ying; Zheng, Yanfang; Li, Ting; Liu, Zhongqiu; Lu, Linlin; Li, Fēi; Tong, Bin; Xiao, Liang; Xu, Xun; Leung, Elaine Lai‐Han; Li, Runze; Yang, Huanming; Wang, Jian; Zhou, Hua; Jia, Huijue; Liu, Liang

doi:10.1186/s40168-019-0719-1

Cited by 119 publications

(83 citation statements)

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“…The universally present species were Streptococcus thermophilus and Bifidobacterium animalis instead of commonly tested probiotics from Lactobacillus . An orally administered strain of B. longum has been shown to persist in 30% of individuals for at least 6 months 87 , while we failed to detect in feces an L. casei strain gavaged to rats 88, 89 , suggesting general differences between Bifidobacterium and Lactobacillus . The strains used by Zmora et al included a number of Lactobacillus , Bifidobacterium , as well as Streptococcus and Lactococcus , all detectable in various gastrointestinal sites despite laxative and colonoscopy 11 .…”

Section: Discussioncontrasting

confidence: 60%

A multi-omic cohort as a reference point for promoting a healthy human gut microbiome

Jie

Liang

Ding

et al. 2019

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1 More than a decade of gut microbiome studies have a common goal for human 2 health. As most of the disease studies sample the elderly or the middle-aged, a 3 reference cohort for young individuals has been lacking. It is also not clear what 4 other omics data need to be measured to better understand the gut microbiome.5 Here we present high-depth metagenomic shotgun sequencing data for the fecal 6 microbiome together with other omics data in a cohort of 2,183 adults, and observe 7 a number of vitamins, hormones, amino acids and trace elements to correlate with 8 the gut microbiome and cluster with T cell receptors. Associations with physical 9 fitness, sleeping habits and dairy consumption are identified in this large multi-omic 1 0 cohort. Many of the associations are validated in an additional cohort of 1,404 1 1 individuals. Our comprehensive data are poised to advise future study designs to 1 2 better understand and manage our gut microbiome both in population and in 1 3 mechanistic investigations.

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Section: Discussioncontrasting

confidence: 60%

A multi-omic cohort as a reference point for promoting a healthy human gut microbiome

Jie

Liang

Ding

et al. 2019

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“…It is now clear that changes in the gut microbiota can impact bone density and health . For example, intestinal infection with pathogenic bacteria can induce bone loss in male mice .…”

Section: Introductionmentioning

confidence: 99%

“…(49) It is now clear that changes in the gut microbiota can impact bone density and health. (50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69) For example, intestinal infection with pathogenic bacteria can induce bone loss in male mice. (70) In contrast, treatment with beneficial bacteria (probiotics) alters gut microbiota composition (50,(53)(54)(55)57,(71)(72)(73)(74) and enhances bone density in healthy male mice, (53) post-antibiotic treated male mice, (68) ovariectomized mice, (50,54,55) inflamed intact female mice, (75) and type 1 diabetic male mice.…”

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confidence: 99%

Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

Schepper

Collins

Rios‐Arce

et al. 2019

Journal of Bone and Mineral Research

133

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Glucocorticoids (GCs) are potent immune‐modulating drugs with significant side effects, including glucocorticoid‐induced osteoporosis (GIO). GCs directly induce osteoblast and osteocyte apoptosis but also alter intestinal microbiota composition. Although the gut microbiota is known to contribute to the regulation of bone density, its role in GIO has never been examined. To test this, male C57/Bl6J mice were treated for 8 weeks with GC (prednisolone, GC‐Tx) in the presence or absence of broad‐spectrum antibiotic treatment (ABX) to deplete the microbiota. Long‐term ABX prevented GC‐Tx‐induced trabecular bone loss, showing the requirement of gut microbiota for GIO. Treatment of GC‐Tx mice with a probiotic (Lactobacillus reuteri [LR]) prevented trabecular bone loss. Microbiota analyses indicated that GC‐Tx changed the abundance of Verrucomicobiales and Bacteriodales phyla and random forest analyses indicated significant differences in abundance of Porphyromonadaceae and Clostridiales operational taxonomic units (OTUs) between groups. Furthermore, transplantation of GC‐Tx mouse fecal material into recipient naïve, untreated WT mice caused bone loss, supporting a functional role for microbiota in GIO. We also report that GC caused intestinal barrier breaks, as evidenced by increased serum endotoxin level (2.4‐fold), that were prevented by LR and ABX treatments. Enhancement of barrier function with a mucus supplement prevented both GC‐Tx–induced barrier leakage and trabecular GIO. In bone, treatment with ABX, LR or a mucus supplement reduced GC‐Tx–induced osteoblast and osteocyte apoptosis. GC‐Tx suppression of Wnt10b in bone was restored by the LR and high‐molecular‐weight polymer (MDY) treatments as well as microbiota depletion. Finally, we identified that bone‐specific Wnt10b overexpression prevented GIO. Taken together, our data highlight the previously unappreciated involvement of the gut microbiota and intestinal barrier function in trabecular GIO pathogenesis (including Wnt10b suppression and osteoblast and osteocyte apoptosis) and identify the gut as a novel therapeutic target for preventing GIO. © 2019 American Society for Bone and Mineral Research.

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“…Interestingly, the two new RA dental markers appeared more abundant in control saliva samples. The strongest marker from healthy saliva remained Lactococcus lactis 5 , and Lactobacillus paracasei, Streptococcus infantarius, w ere identified, reminiscent of beneficial effects of L. casei gavage in rat model of RA 42, 43 . The assembled genomes allowed matching of different species in the Veillonella genus as RA saliva markers.…”

Section: Resultsmentioning

confidence: 98%

Over 50000 metagenomically assembled draft genomes for the human oral microbiome reveal new taxa

Zhu

Liang

Chen

et al. 2019

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21The oral cavity of each person is home for hundreds of bacterial species. While 22 taxa for oral diseases have been well studied using culture-based as well as 23 amplicon sequencing methods, metagenomic and genomic information remain 24 scarce compared to the fecal microbiome. Here we provide metagenomic shotgun 25 data for 3346 oral metagenomics samples, and together with 808 published 26 samples, assemble 56,213 metagenome-assembled genomes (MAGs). 64% of the 27 3,589 species-level genome bins contained no publicly available genomes, others 28 with only a handful. The resulting genome collection is representative of samples 29 around the world and across physiological conditions, contained many genomes 30 from Candidate phyla radiation (CPR) which lack monoculture, and enabled 31 discovery of new taxa such as a family within the Acholeplasmataceae order. 32 New biomarkers were identified for rheumatoid arthritis or colorectal cancer, 33 which would be more convenient than fecal samples. The large number of 34 metagenomic samples also allowed assembly of many strains from important 35 oral taxa such as Porphyromonas and Neisseria. Predicted functions enrich in 36 drug metabolism and small molecule synthesis. Thus, these data lay down a 37 genomic framework for future inquiries of the human oral microbiome. 38 39The human microbiome has been implicated in a growing number of diseases. 40The majority of microbial cells is believed to reside in the large intestine 1 and cohorts 41 with fecal metagenomic data contain over 1000 individuals 2, 3 . For the oral 42 microbiome, hundreds of metagenomic shotgun-sequenced samples have been 43 available from the Human Microbiome Project (HMP) and for rheumatoid arthritis 4-6 . 44A number of other diseases studied by Metagenome-wide association studies (MWAS) 45 using gut microbiome data also indicated potential contribution from the oral 46 microbiome in disease etiology 7-12 . Although the MWAS on rheumatoid arthritis was 47 the oral microbiome is believed to be well covered by culturing 13 , and analyses by 54 16S rRNA gene amplicon sequencing or polymerase chain reaction (PCR) are 55 common. Recently published large-scale metagenomic assembly efforts mostly 56 included fecal metagenomic data [14][15][16] . It is not clear how much is really missing for 57 the oral microbiome. The saliva, in particular, seems to have more bacterial species 58 per individual than the fecal microbiome 17 . 59After getting contigs using assembly algorithms suitable for metagenomic 60 data 18 , a central idea used by metagenomic binning algorithms is that genes or contigs 61 that co-vary in abundance among many samples belong to the same microbial 62 genome 8,[19][20][21] . Large cohorts are therefore prerequisites for high-quality assembly. 63Here we present 3346 new oral metagenomic samples, and 56,213 64 metagenome-assembled genomes (MAGs) which represent 3,589 species-level clades, 65revealing new taxa as well as substantially complementing the genomic content of 66 known species. This ...

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A single bacterium restores the microbiome dysbiosis to protect bones from destruction in a rat model of rheumatoid arthritis

Cited by 119 publications

References 46 publications

A multi-omic cohort as a reference point for promoting a healthy human gut microbiome

A multi-omic cohort as a reference point for promoting a healthy human gut microbiome

Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

Over 50000 metagenomically assembled draft genomes for the human oral microbiome reveal new taxa

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