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Small Intestine Microbiota Regulate Host Digestive and Absorptive Adaptive Responses to Dietary Lipids
Open accessAbstract
The gut microbiota play important roles in lipid metabolism and absorption. However, the contribution of the small bowel microbiota of mammals to these diet-microbe interactions remains unclear. We determine that germ-free (GF) mice are resistant to diet-induced obesity and malabsorb fat with specifically impaired lipid digestion and absorption within the small intestine. Small bowel microbes are essential for host adaptation to dietary lipid changes by regulating gut epithelial processes involved in their digestion and absorption. In addition, GF mice conventionalized with high-fat diet-induced jejunal microbiota exhibit increased lipid absorption even when fed a low-fat diet. Conditioned media from specific bacterial strains directly upregulate lipid absorption genes in murine proximal small intestinal epithelial organoids. These findings indicate that proximal gut microbiota play key roles in host adaptability to dietary lipid variations through mechanisms involving both the digestive and absorptive phases and that these functions may contribute to conditions of over- and undernutrition.
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Al-Baadani, H. H., Al-Mufarrej, S. I., Azzam, M. M., Alharthi, A. S., Al-Garadi, M. A., Al-Gabri, N. A., Al-Abdullatif, A. A., Al-Sagan, A. A., Qaid, M. M., & Alhidary, I. A. (2022) · Tropical Animal Health and Production · doi:10.1007/s11250-022-03245-0 · Cited by 9
“In recent years, there has been increasing interest in the health of broiler chickens to achieve their optimal performance, with the structure and integrity of the intestine, liver, and kidneys providing important information on health status (Martinez-Guryn et al. 2018; Elnesr et al. 2020).”
BackgroundRienzi, S. C. D., Johnson, E. L., Waters, J. L., Kennedy, E. A., Jacobson, J., Lawrence, P., Wang, D. H., Worgall, T. S., Brenna, J. T., & Ley, R. E. (2021) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2021.108808 · Cited by 9
Evans, L., Price, T., Hubert, N., Moore, J., Shen, Y., Athukorala, M., Frese, S. A., Martinez, K., & Ferguson, B. S. (2023) · Biomolecules · doi:10.3390/biom13091274 · Cited by 8
“Quality filtering and downstream analyses were performed using previously published protocols [29].”
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Wang, S., Li, B., Tan, H., Sun, X., Tian, J., Li, S., Xu, Y., Bian, Y., & Wang, Y. (2024) · Food Frontiers · doi:10.1002/fft2.482 · Cited by 8
Kuang, J., Zheng, X., & Jia, W. P. (2024) · Protein & Cell · doi:10.1093/procel/pwae058 · Cited by 10
“…upper intestine’s local microenvironment influences the survival, colonization, and proliferation of microbiota, resulting in a lower bacterial density due to factors such as oxygen presence, rapid transit time, variable pH, and enzymatic activity (Kastl et al., 2020; Martinez-Guryn et al., 2018).”
Li, Y., Zhang, Z., Han, Q., Liu, G., Yin, Y., & Yin, J. (2025) · Science China Life Sciences · doi:10.1007/s11427-024-2794-4 · Cited by 10
“Gut microbiotas are involved in the absorption and deposition of FAs in the host (Martinez-Guryn et al., 2018; Araújo et al., 2020; Yin et al., 2020; Ma et al., 2023; Yin et al., 2023).”
Towards airway microbiome engineering for improving respiratory health
Hern, K. E., & Prindle, A. B. (2025) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2025.115662 · Cited by 8
“…meaning the collection of bacteria, viruses, fungi and archaea that are associated with an individual [13], has been shown to impact several aspects of host heath including digestion [14,15], the immune system [16,17], metabolism [14,15,18] and influences the progression to disease [19 – 22].”
Genetic heterogeneity of colorectal cancer and the microbiome
Senchukova, M. A. (2023) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v15.i3.443 · Cited by 9
Tea polyphenols improve lipid deposition via modulation of gut microbiota in rats and Ningxiang pigs
Wang, Q., Wang, Z., Shang, B., Li, Y., Zhou, F., Zeng, X., Liu, Z., Yang, H., & Zhu, M. (2024) · Journal of Functional Foods · doi:10.1016/j.jff.2024.106049 · Cited by 8
Wan, L., Li, L., Zhang, X., Li, B., Harro, J. M., & Shirtliff, M. E. (2022) · Food Chemistry · doi:10.1016/j.foodchem.2022.134693 · Cited by 8
Metagenomic characterization of the maternal prenatal gastrointestinal microbiome by pregravid BMI
Dreisbach, C., Alhusen, J. L., Prescott, S. M., Dudley, D., Trinchieri, G., & Siega‐Riz, A. M. (2022) · Obesity · doi:10.1002/oby.23659 · Cited by 8
“The Peptostreptococcaceae family regulates lipid absorption in the small intestine, and it was shown to decrease in the ileum and cecum when mice are fed a high-fat diet in a mouse model [27].”
BackgroundLiu, W., Luo, X., Huang, Y. S., Feng, F., & Zhao, M. (2023) · Food Bioscience · doi:10.1016/j.fbio.2023.102944 · Cited by 8
Intestinal organoid technology and applications in probiotics
Tan, H., Chen, X., Wang, C., Song, J., Xu, J., Zhang, Y., & Suo, H. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2023.2288887 · Cited by 9
“Conversely, the effects of Lactobacillus rhamnosus on lipid digestion-related processes were not statistically significant (Martinez-Guryn et al. 2018) (Table 2).”
Gregory, A., Gerhardt, K., Zhong, Z.-P., Bolduc, B., Temperton, B., Konstantinidis, K. T., & Sullivan, M. B. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.01.363960 · Cited by 8
Effect of gum Arabic as natural prebiotic on intestinal ecosystem of post-hatched broiler chicks
Al-Baadani, H. H., Alhotan, R. A., Azzam, M. M., Alhidary, I. A., Alharthi, A. S., & Al-Abdullatif, A. A. (2023) · Journal of Animal Science and Technology · doi:10.5187/jast.2023.e57 · Cited by 7
“Rapid colonization of the gut with commensal bacteria acts as an environmental factor that influences host physiology, metabolism, and gut health [11,12].”
Zhang, Z., Chen, W., Xu, T., Liu, H., Jin, J., Yang, Y., Zhu, X., Han, D., & Xie, S. (2024) · Aquaculture · doi:10.1016/j.aquaculture.2024.742080 · Cited by 7
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“Accumulating evidence from previous studies under-scores the critical role of gut microbiota in maintaining host energy balance [10].”
Zhang, Z., Liu, B., & Ding, S. (2025) · The FASEB Journal · doi:10.1096/fj.202501289r · Cited by 7
“There is compelling evidence that the gut microbiota plays an important part in host metabolic homeostasis [96, 97].”
A newborn derived monoclonal IgM antibody selectively modulates microbial metabolism in the gut
He, Z., Gong, S., Mu, F., Gu, Q., Kundu, P., Gao, Y., Lo‐Man, R., & Draheim, M. (2025) · Nature Communications · doi:10.1038/s41467-025-63585-x · Cited by 7
“Adaptive responses to dietarylipids are regulated by epithelial processes involved in both digestion and absorption 56,57 .”
Understanding the human gut microbiome: from composition to disease association
Alali, M. A., & Shori, A. B. (2026) · Frontiers in Microbiomes · doi:10.3389/frmbi.2026.1717288 · Cited by 11
Dietary Inulin Supplementation Affects Specific Plasmalogen Species in the Brain
Bizeau, J.-B., Albouery, M., Gregoire, S., Buteau, B., Martine, L., Crépin, M., Bron, A. M., Berdeaux, O., Acar, N., Chassaing, B., et al. (2022) · Nutrients · doi:10.3390/nu14153097 · Cited by 7
Lee, J. G., Yun, H. M., Han, G., Lee, G. J., Jeon, C. O., & Hyun, S. (2022) · BMC Biology · doi:10.1186/s12915-022-01458-1 · Cited by 7
“Metabolites produced by microbiota also influence host health [1, 2].”
BackgroundCao, Y., Ibrahim, K. S., Li, X., Wong, A., Wu, Y., Yu, X., Zhou, X., Tan, Z., He, Z., Craft, J. A., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1274401 · Cited by 7
Wang, L., Chen, Y., Yang, Y., Xiao, N., & Lai, C. (2024) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-023-00990-6 · Cited by 7
“Also, small intestine microbiota is important for host adaptive responses to the digestion and absorption of dietary lipids [14].”
BackgroundLong Noncoding RNAs in Diet-Induced Metabolic Diseases
Brandt, A., & Kopp, F. B. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115678 · Cited by 8
“Moreover, intestinal microbiota also seems to affect intestinal lipid absorption [72], and lncRNAs might be able to affect microbiome-host-interaction [73].”
BackgroundKlag, K. A., Bell, R. S., Jia, X., Seguin, A., Maschek, J. A., Bronner, M. P., Cox, J. E., Round, J. L., & Ward, D. M. (2024) · Nutrients · doi:10.3390/nu16121804 · Cited by 9
Dual Regulation Mechanism of Obesity: DNA Methylation and Intestinal Flora
Ren, Y., Huang, P., Zhang, L., Tang, Y.-F., Luo, S., She, Z., Peng, H., Chen, Y.-Q., Luo, J., Duan, W.-X., et al. (2024) · Biomedicines · doi:10.3390/biomedicines12081633 · Cited by 8
“Moreover, a high-fat diet fails to restore the systemic lipid levels of germ-free mice after LFD, which demonstrates the importance of IM in lipid absorption [142].”
BackgroundInfluentialZhang, G., Huang, J., Sun, Z., Guo, Y., Lin, G., Zhang, Z., & Zhao, J. (2024) · Antioxidants · doi:10.3390/antiox13101227 · Cited by 7
“Although the absorption of dietary fats is nearly entirely confined to the small intestine, upon substantial consumption, some fats do reach the colon, where these minute quantities can still exert an influence on colonic microbial ecology [65].”
Background
Metadata
- Authors
- Martinez-Guryn, K., Hubert, N., Frazier, K., Urlass, S., Musch, M. W., Ojeda, P., Pierre, J. F., Miyoshi, J., Sontag, T. J., Cham, C. M., Reardon, C. A., Leone, V., & Chang, E. B.
- Affiliations
- University of Chicago (US)
- Corresponding author
- Chang, Eugene B.
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 23
- Issue
- 4
- Pages
- 458-469.e5
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC5912695
- OpenAlex
- W2796527107
- Cited by
- 663
- References
- 53
- Citations by year
- 2026: 54 · 2025: 85 · 2024: 101 · 2023: 98 · 2022: 88 · 2021: 93 · 2020: 82 · 2019: 43 · 2018: 18
- FWCI
- 21.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK42086)
- Digestive Diseases Research Core Center, University of Chicago (DK097268, T32DK007074)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Keywords
- small intestinal microbiota, dietary fat absorption, lipid digestion, germ-free mice, diet-induced obesity, fat malabsorption, high-fat diet, jejunal microbiota, overnutrition, malnutrition
- MeSH terms
- Gastrointestinal Microbiome, Animals, Diet, Intestine, Small, Lipid Metabolism, Mice
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