Functional Redundancy of Human Microbiome and its Implication in Fecal Microbiota Transplantation

人类微生物组的功能冗余及其在粪便微生物移植中的意义

• 批准号: 10668456
• 负责人: Yang-Yu LIU
• 金额: $ 89.43万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10668456
• 关键词: Behavior; Clinical; Clinical Research; Clostridium difficile; Communities; Complex; Data; Data Analyses; Disease; Ecology; Ecosystem; Engraftment; Gastrointestinal Diseases; Genomics; Goals; Health; Human; Human Microbiome; Infection; Inflammatory Bowel Diseases; Irritable Bowel Syndrome; Knowledge; Measures; Medical; Metagenomics; Methods; Mission; Modification; Nature; Network-based; Obesity; Organism; Outcome; Patients; Phylogenetic Analysis; Physiology; Play; Population; Probability; Public Health; Recurrence; Research; Resistance; Role; Sampling; System; Taxonomy; Testing; Therapeutic Intervention; Translating; United States National Institutes of Health; Whole-Genome Shotgun Sequencing; Work; autism spectrum disorder; dysbiosis; effective therapy; fecal transplantation; gut microbiome; gut microbiota; improved; innovation; microbial community; microbiome; microbiota; microbiota transplantation; microorganism; models and simulation; novel strategies; resilience; stool sample; success; translational impact

Project Summary  Commensal  microorganisms  play  critical  roles  in  human  physiology  and  diseases.  Despite  rapidly  expanding  knowledge  of  the  composition  of  the  human  gut  microbiota,  our  understanding  of  the  ecological  principles  that  govern  the  assembly  and  resilience  of  the  highly  complex  and  dynamic  ecosystem of the gut microbiota is rudimentary. This knowledge gap becomes more problematic as new  approaches  to  modify  the  microbiota,  such  as  fecal  microbiota  transplantation  (FMT),  are  being  developed  as  therapeutic  interventions.  The  overall  objective  of  the  proposed  studies  is  to  construct  an  ecological framework to understand the efficacy of FMT in treating recurrent C. difficile infection (rCDI) at  the  systems  level.  The  central  hypothesis  is  that  the  functional  redundancy  of  the  recipient’s  pre-­FMT  microbiota  can  be  used  to  predict  the  extent  of  donor  microbiota  engraftment  and  predict  the  efficacy  of  FMT.  As  a  classical  concept  in  ecology,  functional  redundancy  (FR)  means  that  phylogenetically  unrelated  species  perform  similar  functions  in  ecosystems  so  that  they  can  be  interchanged  with  little  impact  on  the  overall  ecosystem  functioning.  The  rationale  for  the  proposed  research  is  that  understanding the efficacy of FMT in treating rCDI has the potential to translate into better understanding  of  its  efficacy  in  treating  a  variety  of  other  diseases  associated  with  disrupted  microbiomes.  Guided  by  strong preliminary data, the central hypothesis will be tested by pursuing three specific aims: 1) Develop  a  network-­based  method  to  quantify  the  within-­sample  FR  of  human  microbiome  samples.  The  applicant’s  preliminary  results  suggest  that  the  FR  of  a  microbiome  sample  can  be  calculated  from  its  taxonomic profile and a reference genomic content network. 2) Develop an ecological framework to study  the relationship between the FR of a microbial community and its resistance to new species. The working  hypothesis  is  that  the  higher  the  within-­sample  FR  of  a  microbial  community,  the  more  resistant  it  is  against species addition, e.g., through FMT. Both ecological modeling/simulations and real data analysis  will  be  performed  to  verify  this  hypothesis.  3)  Clinical  study  to  test  that  FMT  has  a  lower  efficacy  in  treating  rCDI  patients  with higher  FR  in  their  pre-­FMT  microbiota.  Stool  samples  from  the  recipients  and  their  respective  donors  will  be  collected  for  metagenomic  whole  genome  shotgun  sequencing.  Subsequently,  the  relationships  among  the  FR  of  the  recipients’  pre-­FMT  microbiota,  the  engraftment  of  donor-­specific species in the recipients’ post-­FMT microbiota, and the FMT efficacy will be quantitatively  analyzed. The approach is innovative because it shifts focus from specific taxa or functions to a systems  level  understanding  of  the  human  gut  microbiome  using  network  and  ecological  approaches.  The  proposed research is significant because it will improve our understanding on the ecological principles of  FMT for rCDI as well for other conditions associated with disrupted microbiomes.

项目总结

项目成果

Structured community transitions explain the switching capacity of microbial systems.

结构化群落转变解释了微生物系统的转换能力。

• DOI: 10.1073/pnas.2312521121
• 发表时间: 2024
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Long,Chengyi;Deng,Jie;Nguyen,Jen;Liu,Yang-Yu;Alm,EricJ;Solé,Ricard;Saavedra,Serguei
• 通讯作者: Saavedra,Serguei

Removal of false positives in metagenomics-based taxonomy profiling via targeting Type IIB restriction sites.

• DOI: 10.1038/s41467-023-41099-8
• 发表时间: 2023-09-01
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Sun, Zheng;Liu, Jiang;Zhang, Meng;Wang, Tong;Huang, Shi;Weiss, Scott T.;Liu, Yang-Yu
• 通讯作者: Liu, Yang-Yu

Gut feelings: associations of emotions and emotion regulation with the gut microbiome in women.

• DOI: 10.1017/s0033291723000612
• 发表时间: 2023-11
• 期刊: PSYCHOLOGICAL MEDICINE
• 影响因子: 6.9
• 作者: Ke, Shanlin;Guimond, Anne-Josee;Tworoger, Shelley S.;Huang, Tianyi;Chan, Andrew T. T.;Liu, Yang-Yu;Kubzansky, Laura D. D.
• 通讯作者: Kubzansky, Laura D. D.

Establishment and resilience of transplanted gut microbiota in aged mice.

老年小鼠移植肠道微生物群的建立和恢复能力

• DOI: 10.1016/j.isci.2021.103654
• 发表时间: 2022-01-21
• 期刊: iScience
• 影响因子: 5.8
• 作者: Wang Y;Tang J;Lv Q;Tan Y;Dong X;Liu H;Zhao N;He Z;Kou Y;Tan Y;Liu XA;Wang L;Liu YY;Dai L
• 通讯作者: Dai L