TY - JOUR
T1 - Identifying determinants of bacterial fitness in a model of human gut microbial succession
AU - Feng, Lihui
AU - Raman, Arjun S.
AU - Hibberd, Matthew C.
AU - Cheng, Jiye
AU - Griffin, Nicholas W.
AU - Peng, Yangqing
AU - Leyn, Semen A.
AU - Rodionov, Dmitry A.
AU - Osterman, Andrei L.
AU - Gordon, Jeffrey I.
N1 - Funding Information:
We thank Maria Karlsson, Marty Meier, Sabrina Wagoner, Su Deng, Justin Serugo, and Jessica Hoisington-L?pez for superb technical assistance; Janaki Guruge for help with culturing human infant bacterial strains; and Barbara Warner and Philip Tarr for their earlier work in establishing a biospecimen repository of serially collected fecal samples from members of the twin birth cohort, an effort that was supported by a grant from Children?s Discovery Institute. Work described in the current study was supported by NIH grant DK30292. L.F. was the recipient of a postdoctoral fellowship from the Helen Hay Whitney Foundation and the Simons Foundation. A.S.R. was supported by the Washington University School of Medicine?s Physician Scientist Training Program. J.I.G. is the recipient of a Thought Leader award from Agilent Technologies.
Funding Information:
ACKNOWLEDGMENTS. We thank Maria Karlsson, Marty Meier, Sabrina Wagoner, Su Deng, Justin Serugo, and Jessica Hoisington-López for superb technical assistance; Janaki Guruge for help with culturing human infant bacterial strains; and Barbara Warner and Philip Tarr for their earlier work in establishing a biospecimen repository of serially collected fecal samples from members of the twin birth cohort, an effort that was supported by a grant from Children’s Discovery Institute. Work described in the current study was supported by NIH grant DK30292. L.F. was the recipient of a postdoctoral fellowship from the Helen Hay Whitney Foundation and the Simons Foundation. A.S.R. was supported by the Washington University School of Medicine’s Physician Scientist Training Program. J.I.G. is the recipient of a Thought Leader award from Agilent Technologies.
Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.
PY - 2020/2/4
Y1 - 2020/2/4
N2 - Human gut microbiota development has been associated with healthy growth but understanding the determinants of community assembly and composition is a formidable challenge. We cultured bacteria from serially collected fecal samples from a healthy infant; 34 sequenced strains containing 103,102 genes were divided into two consortia representing earlier and later stages in community assembly during the first six postnatal months. The two consortia were introduced alone (singly), or sequentially in different order, or simultaneously into young germ-free mice fed human infant formula. The pattern of fitness of bacterial strains observed across the different colonization conditions indicated that later-phase strains substantially outcompete earlier-phase strains, although four early-phase members persist. Persistence was not determined by order of introduction, suggesting that priority effects are not prominent in this model. To characterize succession in the context of the metabolic potential of consortium members, we performed in silico reconstructions of metabolic pathways involved in carbohydrate utilization and amino acid and B-vitamin biosynthesis, then quantified the fitness (abundance) of strains in serially collected fecal samples and their transcriptional responses to different histories of colonization. Applying feature-reduction methods disclosed a set of metabolic pathways whose presence and/or expression correlates with strain fitness and that enable early-stage colonizers to survive during introduction of later colonizers. The approach described can be used to test the magnitude of the contribution of identified metabolic pathways to fitness in different community contexts, study various ecological processes thought to govern community assembly, and facilitate development of microbiota-directed therapeutics.
AB - Human gut microbiota development has been associated with healthy growth but understanding the determinants of community assembly and composition is a formidable challenge. We cultured bacteria from serially collected fecal samples from a healthy infant; 34 sequenced strains containing 103,102 genes were divided into two consortia representing earlier and later stages in community assembly during the first six postnatal months. The two consortia were introduced alone (singly), or sequentially in different order, or simultaneously into young germ-free mice fed human infant formula. The pattern of fitness of bacterial strains observed across the different colonization conditions indicated that later-phase strains substantially outcompete earlier-phase strains, although four early-phase members persist. Persistence was not determined by order of introduction, suggesting that priority effects are not prominent in this model. To characterize succession in the context of the metabolic potential of consortium members, we performed in silico reconstructions of metabolic pathways involved in carbohydrate utilization and amino acid and B-vitamin biosynthesis, then quantified the fitness (abundance) of strains in serially collected fecal samples and their transcriptional responses to different histories of colonization. Applying feature-reduction methods disclosed a set of metabolic pathways whose presence and/or expression correlates with strain fitness and that enable early-stage colonizers to survive during introduction of later colonizers. The approach described can be used to test the magnitude of the contribution of identified metabolic pathways to fitness in different community contexts, study various ecological processes thought to govern community assembly, and facilitate development of microbiota-directed therapeutics.
KW - Feature-reduction algorithms
KW - Gut microbiome
KW - Metabolic pathways
KW - Microbial community assembly/succession
UR - http://www.scopus.com/inward/record.url?scp=85079018548&partnerID=8YFLogxK
U2 - 10.1073/pnas.1918951117
DO - 10.1073/pnas.1918951117
M3 - Article
C2 - 31969452
AN - SCOPUS:85079018548
VL - 117
SP - 2622
EP - 2633
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 5
ER -