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Peer-reviewedCC BYGut Microbes

A stratified human colon model reveals SCFA cross-feeding-driven host–microbe dynamics associated with epithelial and immune responses

  • Taewon Kim1
  • Joon-Young Park2
  • Minae Kim1
  • Na Young Kim1
  • Seol-A Jang2
  • Han-Gyeol Park3
  • Dong-Woo Lee4
  • Keunwook Lee3
  • Bong-Soo Kim5,6,7
  • Nam Joo Kang1
7 affiliations
  1. 1Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea.
  2. 2Department of Life Science, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
  3. 3Department of Biomedical Sciences, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.
  4. 4Department of Biotechnology, Yonsei University, Seoul, Republic of Korea.
  5. 5Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Republic of Korea.
  6. 6Global Food and Nutrition Research Institute, Ewha Womans University, Seoul, Republic of Korea.
  7. 7Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, Republic of Korea.
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Abstract

Host–microbe interactions are essential for maintaining intestinal homeostasis, yet most in vitro models lack physiological oxygen gradients, mucosal architecture, and reproducibility. We developed the Mucosal Mimetic 3D–Host Aerobic Microbiota Anaerobic Co-culture (Mm 3D-HaeMan) system, a colon-mimetic, oxygen-stratified platform enabling stable co-culture of colonic epithelial cells, human peripheral blood mononuclear cells (hPBMCs), and obligate anaerobes. Oxygen profiling confirmed a stable gradient consistent with human colonic stratification. Using a canonical short-chain fatty acid (SCFA) cross-feeding pair (Anaerostipes caccae and Bifidobacterium bifidum, AcBb consortium), we performed integrated, multilayered analyzes of the host-microbe interface. Co-culture with the SCFA-producing AcBb consortium was associated with enhanced epithelial-mitochondrial respiration, maintenance of transepithelial resistance, tight junction protein expression without barrier disruption, and rebalanced cytokine profiles. Host transcriptomics identified 41 differentially expressed genes (15 upregulated, 26 downregulated) associated with homeostatic-relevant epithelial responses. Simultaneously, bacterial metatranscriptomics revealed 29 differentially expressed gene families; notably, glaK was enriched in bacteria-only cultures; SORD, nuoG, and nuoE were specifically induced during co-culture, indicating host-associated bacterial transcriptional changes. The compartmentalized design permits independent sampling for layer-resolved multi-omics and functional readouts. These findings establish Mm 3D-HaeMan as a physiologically grounded platform for dissecting bidirectional host–microbe responses and immune-associated interactions. This model offers broad applicability for mechanistic research and translational screening of probiotics and microbiome-based therapeutics.

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Cite

BibTeXRIS
BibTeX
@article{kim2026stratified,
  title = {{A stratified human colon model reveals SCFA cross-feeding-driven host–microbe dynamics associated with epithelial and immune responses}},
  author = {Taewon Kim and Joon-Young Park and Minae Kim and Na Young Kim and Seol-A Jang and Han-Gyeol Park and Dong-Woo Lee and Keunwook Lee and Bong-Soo Kim and Nam Joo Kang},
  journal = {Gut Microbes},
  year = {2026},
  month = oct,
  doi = {10.1080/19490976.2026.2749954},
  url = {https://doi.org/10.1080/19490976.2026.2749954},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - A stratified human colon model reveals SCFA cross-feeding-driven host–microbe dynamics associated with epithelial and immune responses
AU  - Taewon Kim
AU  - Joon-Young Park
AU  - Minae Kim
AU  - Na Young Kim
AU  - Seol-A Jang
AU  - Han-Gyeol Park
AU  - Dong-Woo Lee
AU  - Keunwook Lee
AU  - Bong-Soo Kim
AU  - Nam Joo Kang
PY  - 2026
DA  - 2026/10/23
JO  - Gut Microbes
DO  - 10.1080/19490976.2026.2749954
UR  - https://doi.org/10.1080/19490976.2026.2749954
AB  - Host–microbe interactions are essential for maintaining intestinal homeostasis, yet most in vitro models lack physiological oxygen gradients, mucosal architecture, and reproducibility. We developed the Mucosal Mimetic 3D–Host Aerobic Microbiota Anaerobic Co-culture (Mm 3D-HaeMan) system, a colon-mimetic, oxygen-stratified platform enabling stable co-culture of colonic epithelial cells, human peripheral blood mononuclear cells (hPBMCs), and obligate anaerobes. Oxygen profiling confirmed a stable gradient consistent with human colonic stratification. Using a canonical short-chain fatty acid (SCFA) cross-feeding pair (Anaerostipes caccae and Bifidobacterium bifidum, AcBb consortium), we performed integrated, multilayered analyzes of the host-microbe interface. Co-culture with the SCFA-producing AcBb consortium was associated with enhanced epithelial-mitochondrial respiration, maintenance of transepithelial resistance, tight junction protein expression without barrier disruption, and rebalanced cytokine profiles. Host transcriptomics identified 41 differentially expressed genes (15 upregulated, 26 downregulated) associated with homeostatic-relevant epithelial responses. Simultaneously, bacterial metatranscriptomics revealed 29 differentially expressed gene families; notably, glaK was enriched in bacteria-only cultures; SORD, nuoG, and nuoE were specifically induced during co-culture, indicating host-associated bacterial transcriptional changes. The compartmentalized design permits independent sampling for layer-resolved multi-omics and functional readouts. These findings establish Mm 3D-HaeMan as a physiologically grounded platform for dissecting bidirectional host–microbe responses and immune-associated interactions. This model offers broad applicability for mechanistic research and translational screening of probiotics and microbiome-based therapeutics.
SN  - 1949-0984
SN  - 1949-0976
ER  -