Distinct microbial and immune niches of the human colon


Gastrointestinal microbiota and immune cells interact closely and display regional specificity; however, little is known about how these communities differ with location. Here, we simultaneously assess microbiota and single immune cells across the healthy, adult human colon, with paired characterization of immune cells in the mesenteric lymph nodes, to delineate colonic immune niches at steady state. We describe distinct helper T cell activation and migration profiles along the colon and characterize the transcriptional adaptation trajectory of regulatory T cells between lymphoid tissue and colon. Finally, we show increasing B cell accumulation, clonal expansion and mutational frequency from the cecum to the sigmoid colon and link this to the increasing number of reactive bacterial species.

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Fig. 1: Variation in the microbiome from proximal to distal colon.
Fig. 2: Profiling immune cells along the steady-state colon.
Fig. 3: Dissemination of helper T cells in the colon and region-determined transcriptional profiles.
Fig. 4: Treg activation pathway from lymphoid to peripheral tissue.
Fig. 5: B cells are more abundant, clonally expanded and mutated in the sigmoid colon.
Fig. 6: Increasing number of microbiome species recognized by antibodies in the sigmoid colon.

Data availability

Raw sequencing data files are available at ArrayExpress (accession nos. E-MTAB-8007, E-MTAB-8474, E-MTAB-8476, E-MTAB-8484 and E-MTAB-8486). Sequencing data for the microbiome are available at MGnify. (ERA numbers are listed in Supplementary Table 6.) Processed scRNA-seq data are available for online visualization and download at the Gut Cell Atlas (https://www.gutcellatlas.org/).


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We acknowledge the support received from the Wellcome Sanger Cytometry Core Facility, Cellular Genetics Informatics team and Core DNA Pipelines. We thank F. Rouhani and T. Castro-Dopico for insightful discussions about project and experimental design and K. Mahbubani for help with the collection of human tissue. We acknowledge J. Eliasova for the graphical images. This research was supported by funding from the Wellcome Trust (grant no. WT206194 to S.A.T.) and the European Research Council (grant no. 646794 ThDEFINE to S.A.T.). K.R.J. holds a Non-Stipendiary Junior Research Fellowship from Christ’s College, University of Cambridge. T.G. was funded by the European Union’s H2020 research and innovation programme ‘ENLIGHT-TEN’ under Marie Skłodowska-Curie grant agreement no. 675395. H.W.K. was funded by a Sir Henry Wellcome Postdoctoral Fellowship (grant no. 213555/Z/18/Z). B.R.B. was funded by the NIHR Cambridge Biomedical Research Centre (grant no. RG92051). We thank the deceased organ donors, donor families and the Cambridge Biorepository for Translational Medicine for access to the tissue samples. This publication is part of the Human Cell Atlas (https://www.humancellatlas.org/publications/).

Author information




K.R.J. initiated this project, designed and performed the scRNA-seq and microbiome experiments, analyzed the data and wrote the manuscript. T.G. analyzed the bulk BCR-seq data and contributed extensively to the scRNA-seq data analysis. R.E. contributed to data interpretation and scRNA-seq data analysis. N.K. and E.L.G. analyzed the 16S ribosomal sequencing and metagenomics data. M.D.S. assisted in the microbiome-related experiments. H.W.K. and L.K.J. analyzed the 10x Genomics VDJ datasets and contributed to the generation of figures. B.R.B. and K.S.P. carried out the tissue collection. J.R.F. designed the flow-sorting panel and assisted with flow-sorting. V.N.P. assisted with bulk BCR library preparation and analysis. L.B.J., O.S., S.H. and J.L.J. dissociated tissues from donor 390c. K.P. carried out the scRNA-seq read alignment and quality control. S.C.F., K.B.M. and M.R.C. designed the experiments and interpreted the data. T.D.L. and S.A.T. initiated and supervised the project and interpreted the data. All authors edited the paper.

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Correspondence to Kylie R. James or Sarah A. Teichmann.

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S.C.F. and T.D.L. are either employees of, or consultants to, Microbiotica.

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Editor recognition statement Zoltan Fehervari was the primary editor(s) on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

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James, K.R., Gomes, T., Elmentaite, R. et al. Distinct microbial and immune niches of the human colon. Nat Immunol 21, 343–353 (2020). https://doi.org/10.1038/s41590-020-0602-z

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