Cited by 527Gut microbiota and healthGastrointestinal motility and disordersProbiotics and Fermented Foods

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Modulation of intestinal barrier by intestinal microbiota: Pathological and therapeutic implications

Natividad, Jane M.M., Verdu, Elena F.·2013·Pharmacological Research

DOI 10.1016/j.phrs.2012.10.007

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Abstract

Mammals and their intestinal microbiota peacefully coexist in a mutualistic relationship. Commensal bacteria play an active role in shaping and modulating physiological processes in the host, which include, but are not restricted to, the immune system and the intestinal barrier. Both play a crucial role in containing intestinal bacteria and other potentially noxious luminal antigens within the lumen and mucosal compartment. Although mutualism defines the relationship between the host and the intestinal microbiota, disruptions in this equilibrium may promote disease. Thus, alterations in gut microbiota (dysbiosis) have been linked to the recent increased expression of obesity, allergy, autoimmunity, functional and inflammatory disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). In this article, we review the evidence supporting a role of gut microbiota in regulating intestinal barrier function. We discuss the hypothesis that microbial factors can modulate the barrier in ways that can prevent or promote gastrointestinal disease. A better understanding of the role of the intestinal microbiota in maintaining a functional intestinal barrier may help develop targeted strategies to prevent and treat disease.

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Crossref · 10.1016/j.phrs.2012.10.007

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“…microbiota is crucial for the proper functioning of the mucosal immune system (Thursby and Juge, 2017) and to maintain mucosal barrier integrity (Natividad and Verdu, 2013), amongst many other benefits to the host, such as e.g. protection against pathogens (B ¨ aumler and Sper-andio, 2016) and…”
Dietary Interventions Ameliorate Infectious Colitis by Restoring the Microbiome and Promoting Stem Cell Proliferation in Mice
Ahmed, I., Yusuf, K., Roy, B. C., Stubbs, J. R., Anant, S., Attard, T. M., Sampath, V., & Umar, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010339 · Cited by 16
“The gut’s protective effects against external insults depend on the activity of a functional intestinal epithelium which is constantly maintained by the continuous and rapid proliferation of undifferentiated cells located within the crypts [13].”
Anti-tumor necrosis factor α therapy associates to type 17 helper T lymphocytes immunological shift and significant microbial changes in dextran sodium sulphate colitis
Petito, V., Graziani, C., Lopetuso, L. R., Fossati, M., Battaglia, A., Arena, V., Scannone, D., Quaranta, G., Quagliariello, A., CHIERICO, F. D., et al. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i12.1465 · Cited by 15
Impact of Fruit Dietary Fibers and Polyphenols on Modulation of the Human Gut Microbiota
Quirós-Sauceda, A. E., Pacheco‐Ordaz, R., Ayala-Zavala, J. F., Hernández‐Mendoza, A., González-Córdova, A. F., Vallejo‐Galland, B., & González-Aguilar, G. A. (2017) · Wiley eBooks · doi:10.1002/9781119158042.ch19 · Cited by 15
Altered intestinal microflora and barrier injury in severe acute pancreatitis can be changed by zinc
Su, S., & Tang, Q. (2021) · International Journal of Medical Sciences · doi:10.7150/ijms.45980 · Cited by 14
In Vitro Fermentation of Pleurotus eryngii Mushrooms by Human Fecal Microbiota: Metataxonomic Analysis and Metabolomic Profiling of Fermentation Products
Christodoulou, P., Vlassopoulou, M., Zervoú, M., Xanthakos, E., Moulos, P., Koutrotsios, G., Zervakis, G. I., Kerezoudi, E. N., Mitsou, E. K., Saxami, G., et al. (2023) · Journal of Fungi · doi:10.3390/jof9010128 · Cited by 16
“Its composition is remarkably diverse and demonstrates great variability across individuals, as more than 1800 genera and 15,000–36,000 species are potential gut inhabitants [16], with the distal gut being dominated by the phyla Bacteroidetes and Firmicutes (>90%) [13,17].”
Background
Glutamine Peptides: Preparation, Analysis, Applications, and Their Role in Intestinal Barrier Protection
Wang, J., He, Y., Liu, Z., Liu, X., & Jing, Y. (2025) · Nutrients · doi:10.3390/nu17061017 · Cited by 14
“…most researchers still use synthetic glutamine dipeptides as the research object to study their physiological function in the human body or animal body, while as mentioned above, the synthetic method has the disadvantages of high cost, complicated process, environmental pollution and so on.”
Impaired gastric mucosal integrity identified by confocal endomicroscopy in Helicobacter pylori‐negative functional dyspepsia
Ji, R., Wang, P., Kou, G., Zuo, X., Wang, X., & Li, Y. (2019) · Neurogastroenterology & Motility · doi:10.1111/nmo.13719 · Cited by 14
Higher bacterial DNAemia can affect the impact of a polyphenol-rich dietary pattern on biomarkers of intestinal permeability and cardiovascular risk in older subjects
Gargari, G., Taverniti, V., Bo’, C. D., Bernardi, S., Hidalgo‐Liberona, N., Meroño, T., Andrés‐Lacueva, C., Kroon, P. A., Cherubini, A., Riso, P., et al. (2021) · European Journal of Nutrition · doi:10.1007/s00394-021-02680-3 · Cited by 14
“In particular, the intestinal microbial ecosystem plays an active role in both immune responses and intestinal barrier integrity [9].”
Background
Editorial: Human Microbiome: Symbiosis to Pathogenesis
Lee, L., Wong, S. H., Chin, S., Singh, V., & Mutalib, N. A. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.605783 · Cited by 17
“The dysbiosis can occur due to overgrowth or invasion of pathogens in the gut, compromising the gut epithelial barrier integrity and exacerbating inflammation (Natividad and Verdu, 2013; Zhang et al., 2015; Wong et al., 2017).”
Background
Effects of probiotic supplementation on the gut microbiota composition of adults: a systematic review of randomized clinical trials
Mörschbächer, A. P., Pappen, E., Henriques, J. A. P., & Granada, C. E. (2023) · Anais da Academia Brasileira de Ciências · doi:10.1590/0001-3765202320230037 · Cited by 15
“…epithelial cell proliferation and differentiation (Sekirov et al. 2010); strengthening gut integrity or shaping the intestinal epithelium (Natividad & Verdu 2013); acting on nutrient uptake, vitamin synthesis, and energy harvesting (Ursell et al. 2012); protecting against pathogens…”
Background
Unveiling the relationship between gut microbiota and heart failure: Recent understandings and insights
Jain, H., Marsool, M. D. M., Goyal, A., Sulaiman, S. A., Fatima, L., Idrees, M., Sharma, B., Borra, V., Gupta, P., Nadeem, A., et al. (2023) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2023.102179 · Cited by 13
Causal relationship between gut microbiota and autoimmune thyroiditis: A mendelian study
Xiong, Y., Zhu, X., & Luo, Q. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e25652 · Cited by 16
“Specifically, the gut microbiota is known to contribute to the production of various metabolites, including short-chain fatty acids (SCFAs), which serve to mitigate bacterial translocation, uphold intestinal integrity, and curtail intestinal inflammation [18].”
Background
Microbiota and Digestive Metabolites Alterations in Functional Dyspepsia
Fărcaș, R. A., Grad, S., Grad, C., & Dumitrascu, D. L. (2024) · Journal of Gastrointestinal and Liver Diseases · doi:10.15403/jgld-5024 · Cited by 13
β-1,3-glucans from Euglena Gracilis protects against ulcerative colitis via modulating the gut barrier, T-cell immunity and gut microbiota
Guo, B., Zhang, W., Zou, J., Sun, L., Dong, N., & Liu, B. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.141288 · Cited by 13
Hydroxytyrosol Ameliorates Colon Inflammation: Mechanistic Insights into Anti-Inflammatory Effects, Inhibition of the TLR4/NF-κB Signaling Pathway, Gut Microbiota Modulation, and Liver Protection
Tang, J., Zhang, M., Wang, J., Zhang, H., Wang, Z., Lei, Z., Wang, C., & Chen, W. (2025) · Foods · doi:10.3390/foods14071270 · Cited by 14
“Disruption of the gut microbiota and impairment of the gut barrier can lead to increased permeability and translocation of microbial products, which can then reach the liver and potentially activate the hepatic toll-like receptor 4 (TLR4) signaling pathway [17,18].”
Fisiologia da Barreira Epitelial Intestinal
Rodrigues, F. A. P., de Medeiros, P. H. Q. S., Prata, M. D. M. G., & Lima, A. Â. M. (2016) · Editora Blucher eBooks · doi:10.5151/9788580391893-18 · Cited by 12
Effects of a farm-specific fecal microbial transplant (FMT) product on clinical outcomes and fecal microbiome composition in preweaned dairy calves
Slanzon, G. S., Ridenhour, B. J., Parrish, L. M., Trombetta, S. C., Moore, D. A., Sischo, W. M., & McConnel, C. S. (2022) · PLoS ONE · doi:10.1371/journal.pone.0276638 · Cited by 12
A new strategy for treating colorectal cancer: Regulating the influence of intestinal flora and oncolytic virus on interferon
Yi, J., Lin, P., Li, Q., Zhang, A., & Kong, X. (2023) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2023.08.010 · Cited by 17
The Role of the Gut Microbiome in Hematological Cancers
Hussein, N., Rajasuriar, R., Khan, A. M., Lim, Y. A. L., & Gan, G. G. (2023) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-23-0080 · Cited by 12
Emerging implications of bacterial biofilm in cancer biology: Recent updates and major perspectives
Kushwaha, M., Nukala, V., Singh, A. K., Makharia, G. K., Mohan, A., Kumar, A., & Dalal, N. (2024) · Gut Microbes Reports · doi:10.1080/29933935.2024.2339270 · Cited by 13
Causal relationships between the gut microbiota, inflammatory cytokines, and alcoholic liver disease: a Mendelian randomization analysis
Li, S., Zhou, C., Liu, T., Zhang, L., Liu, S., Zhao, Q., Liu, J., & Zhao, W. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1442603 · Cited by 13
Antihypertensive effects of rice peptides involve intestinal microbiome alterations and intestinal inflammation alleviation in spontaneously hypertensive rats
Li, J., Wei, W., Ma, X., Ji, J., Ling, X., Xu, Z., Guan, Y., Zhou, L., Wu, Q., Huang, W., et al. (2024) · Food & Function · doi:10.1039/d4fo04251d · Cited by 12
The pelvic flexure separates distinct microbial communities in the equine hindgut
Reed, K. J., Kunz, I. G. Z., Scare, J. A., Nielsen, M. K., Turk, P. J., Coleman, R., & Coleman, S. J. (2021) · Scientific Reports · doi:10.1038/s41598-021-83783-z · Cited by 13
Microbiota-Gut-Brain Axis in Neurological Disorders: From Leaky Barriers Microanatomical Changes to Biochemical Processes
Boschetti, E., Neri, I., Follo, M. Y., GIORGIO, R. D., Cocco, L., Manzoli, L., & Ratti, S. (2022) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557522666220622111501 · Cited by 13
Hot-Melt Extrusion Enhances Antioxidant Effects of Mulberry on Probiotics and Pathogenic Microorganisms
Go, E. J., Ryu, B. R., Gim, G.-J., Lee, H. Y., You, H.-S., Kim, H., Lee, H. T., Lee, J. Y., Shim, M. S., Baek, J.-S., et al. (2022) · Antioxidants · doi:10.3390/antiox11112301 · Cited by 12
Perinatal exposure to foodborne inorganic nanoparticles: A role in the susceptibility to food allergy?
Issa, M., Rivière, G., Houdeau, É., & Adel‐Patient, K. (2022) · Frontiers in Allergy · doi:10.3389/falgy.2022.1067281 · Cited by 12
Impacts of Habitual Diets Intake on Gut Microbial Counts in Healthy Japanese Adults
Sugimoto, T., Shima, T., Amamoto, R., Kaga, C., Kado, Y., Watanabe, O., Shiinoki, J., Iwazaki, K., Shigemura, H., Tsuji, H., et al. (2020) · Nutrients · doi:10.3390/nu12082414 · Cited by 12
Citri Reticulatae Pericarpium modulates gut microbiota: Impacts on human health
Cai, Y., Ma, W., Hou, Y., Nisar, M. F., Long, Y., Chen, B., Zhang, X., Huang, L. T., Zheng, G., Yan, T., et al. (2025) · Food Research International · doi:10.1016/j.foodres.2025.116745 · Cited by 13
Preterm Delivery: Microbial Dysbiosis, Gut Inflammation and Hyperpermeability
Arboleya, S., Ríos-Covián, D., Maillard, F., Langella, P., Gueimonde, M., & Martín, R. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.806338 · Cited by 14
Understanding the roles of the microbiome in autoimmune rheumatic diseases
Amarnani, A., & Silverman, G. J. (2023) · Rheumatology and Immunology Research · doi:10.2478/rir-2023-0027 · Cited by 13
“[3,4] While some studies have shown a correlation between gut microbiota imbalances (also termed dysbiosis) and inflammatory and autoimmune conditions, [5] recent re ports have suggested that the overgrowth, or bloom, of typi cally harmless gut bacteria can perturb the gut epithelial bar rier…”
Background
The silent threat: Nanopolystyrene and chrysene pollutants disrupt the intestinal mucosal barrier, new insights from juvenile Siniperca chuatsi
Chen, T., Aly, R. S. S., Shen, Y., Tang, S., Zhao, Y., Zhao, J., & Chen, X. (2024) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2024.172001 · Cited by 11
Modulation of gut microbiota in targeted cancer therapy: insights on the EGFR/VEGF/KRAS pathways
Gong, L., Yang, S., Huang, J., & Li, Y. (2024) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2024.0320 · Cited by 11
“While the gut microbiota have an essential role in various physiologic functions, the gut microbiota are also associated with a range of diseases, including neurodegenerative disorders 10 , psychological disorders 11 , and inflammatory disorders 12 .”
Oral Exposure to Epoxiconazole Disturbed the Gut Micro-Environment and Metabolic Profiling in Male Mice
Weng, Y. Z., Xu, T., Wang, C., & Jin, Y. (2023) · Metabolites · doi:10.3390/metabo13040522 · Cited by 11
“The intestinal barrier prevents foreign substances from entering the body through microbial recognition, mucus secretion, tight junction, AMP production, and ion transport [20].”
Background
Site-specific impact of polyphenols on the gastrointestinal microbiome
Ebrahimi, F., Subbiah, V., Ağar, O. T., Legione, A. R., & Suleria, H. A. R. (2024) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2024.2434961 · Cited by 10
“…microbiota is an essential factor in maintaining our homeostasis through various pathways, such as affecting intestinal barrier functions (Natividad and Verdu 2013), metabolic pathways (Andreu et al. 2021), host signaling (Schroeder and Bäckhed 2016), immune-inflammatory functions…”
AQP3 mediates autophagy through SIRT1/p62 signal to alleviate intestinal epithelial cell damage caused by sepsis
Wang, C., Hu, Y., Song, Y., & Hu, X. (2024) · International Journal of Colorectal Disease · doi:10.1007/s00384-024-04788-4 · Cited by 10
Unveiling the Neurotoxic Effects of Ochratoxin A and Its Impact on Neuroinflammation
García-Esparza, M. Á., Mateo, E. M., Robles, J. A., Capoferri, M., Jiménez, M., & Soria, J. M. (2025) · Toxins · doi:10.3390/toxins17060264 · Cited by 11
“…the gut lining is composed of four principal intestinal cell types: absorptive enterocytes, which form the majority of the cellular components; protective mucus-producing goblet cells; Paneth cells, which generate antimicrobial peptides (AMPs); and hormone-secreting enteroendocrine cells [39].”
Effects of Replacing Fishmeal and Soybean Protein Concentrate with Degossypolized Cottonseed Protein in Diets on Growth Performance, Nutrient Digestibility, Intestinal Morphology, Cecum Microbiome and Fermentation of Weaned Piglets
Wang, L., Gao, W., Shi, H., Hu, Q., & Lai, C. (2022) · Animals · doi:10.3390/ani12131667 · Cited by 10
“The gut microbiota offers many benefits to the host through a range of physiological functions such as strengthening gut integrity or shaping the intestinal epithelium [26].”
Background
Administration of the probiotic Lactiplantibacillus paraplantarum is effective in controlling hyperphosphatemia in 5/6 nephrectomy rat model
Moon, S. J., Hwang, J., Kang, W. K., Ahn, J.-P., & Kim, H. J. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120856 · Cited by 10

Authors: Natividad, J. M. M., & Verdu, E. F.
Affiliations: McMaster University (CA)
Corresponding author: Verdu, Elena F.
ORCID: Verdu, Elena F.
Venue: Pharmacological Research
Publisher: Elsevier BV
Published: 2013-03
Volume: 69
Issue: 1
Pages: 42-51
ISSN: 1043-6618 (ISSN-L)
DOI: 10.1016/j.phrs.2012.10.007
OpenAlex: W2149848289
Cited by: 525
References: 146
Citations by year: 2026: 30 · 2025: 44 · 2024: 68 · 2023: 79 · 2022: 56 · 2021: 65 · 2020: 53 · 2019: 45 · 2018: 23 · 2017: 19 · 2016: 11 · 2015: 13 · 2014: 12 · 2013: 7
FWCI: 0.93
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Pharmacological Research (publishedVersion)
PubMed (publishedVersion)
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 › Food Science › Probiotics and Fermented Foods
Keywords: intestinal barrier, gut microbiota, dysbiosis, commensal bacteria, host-microbe mutualism, obesity, allergy, autoimmunity, irritable bowel syndrome, inflammatory bowel disease, gastrointestinal diseases, treatment options
MeSH terms: Animals, Gastrointestinal Diseases, Humans, Intestines, Bacterial Physiological Phenomena, Metagenome

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Modulation of intestinal barrier by intestinal microbiota: Pathological and therapeutic implications

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