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Peer-reviewedCC BYAntibiotics (Basel, Switzerland)

Novel Therapeutic Strategies for Active Crohn's Disease: Targeting Pathobionts and Host-Microbe Interactions.

  • Gaetano Iaquinto1
  • Errico Picariello2
  • Salvatore Iaquinto3
  • Raffaele Melina4
  • Carmine Sellitto5
  • Simone Sellitto1
  • Giovanna Cataldo6
  • Raffaele Pastore7
  • Vera Rotondi Aufiero2,8
8 affiliations
  1. 1Gastroenterology Department, St. Rita Hospital, NefroCenter Group, 83042 Atripalda, Italy.
  2. 2Institute of Food Sciences, Consiglio Nazionale Delle Ricerche (CNR), 83100 Avellino, Italy.
  3. 3Gastroenterology Unit, St. Filippo Neri Hospital, 00135 Rome, Italy.
  4. 4Gastroenterology Unit, San G. Moscati Hospital, 83100 Avellino, Italy.
  5. 5Department of Medical and Surgical Specialities and Dentistry, University of Campania Luigi Vanvitelli, 81100 Naples, Italy.
  6. 6Section of Human Anatomy, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
  7. 7Department of Medicine and Health Sciences 'Vincenzo Tiberio', University of Molise, 86100 Campobasso, Italy.
  8. 8European Laboratory for the Investigation of Food Induced Diseases, Hosted Within the Pediatric Section of the Department of Medical Translational Sciences Via S. Pansini 5, 80131 Naples, Italy.
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Abstract

Crohn's disease (CD) is a chronic inflammatory disorder characterized by complex interactions among genetic susceptibility, environmental factors, dysregulated immune responses, and alterations of the intestinal microbiota. Although corticosteroids, immunomodulators, biologics, and advanced small-molecule therapies remain central to disease management, a substantial proportion of patients experience primary non-response, loss of response, or treatment-related adverse effects. This has stimulated interest in complementary therapeutic strategies targeting host-microbe interactions and intestinal microbial homeostasis. This review critically examines emerging microbiome-directed approaches for CD, with particular emphasis on pathobionts such as adherent-invasive Escherichia coli (AIEC). We discuss the available evidence for antibiotics, antimicrobial peptides (AMP), gut bacteriophages, fecal microbiota transplantation (FMT), and selected nutraceutical and dietary interventions. While some approaches show promising biological or clinical signals, the strength of evidence varies considerably, ranging from in vitro and animal studies to randomized clinical trials and meta-analyses. Antibiotic therapies targeting intestinal pathogens have shown heterogeneous results, suggesting the need for pathogen-guided and intracellularly active antimicrobial strategies. Novel approaches, including AIEC-specific phages and AMP-based interventions, represent promising microbiome-sparing alternatives capable of selectively modulating disease-associated microorganisms. Furthermore, FMT and nutraceuticals may contribute to restoring microbial balance and strengthening intestinal homeostasis, although their efficacy requires further validation in controlled clinical trials. Overall, these strategies support a transition toward precision medicine approaches integrating microbial profiling, host immune characterization, and targeted antimicrobial interventions to improve therapeutic outcomes in CD.

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Cite

BibTeXRIS
BibTeX
@article{iaquinto2026novel,
  title = {{Novel Therapeutic Strategies for Active Crohn's Disease: Targeting Pathobionts and Host-Microbe Interactions.}},
  author = {Gaetano Iaquinto and Errico Picariello and Salvatore Iaquinto and Raffaele Melina and Carmine Sellitto and Simone Sellitto and Giovanna Cataldo and Raffaele Pastore and Vera Rotondi Aufiero},
  journal = {Antibiotics (Basel, Switzerland)},
  year = {2026},
  month = sep,
  doi = {10.3390/antibiotics15100964},
  url = {https://europepmc.org/article/MED/42938706},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Novel Therapeutic Strategies for Active Crohn's Disease: Targeting Pathobionts and Host-Microbe Interactions.
AU  - Gaetano Iaquinto
AU  - Errico Picariello
AU  - Salvatore Iaquinto
AU  - Raffaele Melina
AU  - Carmine Sellitto
AU  - Simone Sellitto
AU  - Giovanna Cataldo
AU  - Raffaele Pastore
AU  - Vera Rotondi Aufiero
PY  - 2026
DA  - 2026/09/30
JO  - Antibiotics (Basel, Switzerland)
DO  - 10.3390/antibiotics15100964
UR  - https://europepmc.org/article/MED/42938706
AB  - Crohn's disease (CD) is a chronic inflammatory disorder characterized by complex interactions among genetic susceptibility, environmental factors, dysregulated immune responses, and alterations of the intestinal microbiota. Although corticosteroids, immunomodulators, biologics, and advanced small-molecule therapies remain central to disease management, a substantial proportion of patients experience primary non-response, loss of response, or treatment-related adverse effects. This has stimulated interest in complementary therapeutic strategies targeting host-microbe interactions and intestinal microbial homeostasis. This review critically examines emerging microbiome-directed approaches for CD, with particular emphasis on pathobionts such as adherent-invasive Escherichia coli (AIEC). We discuss the available evidence for antibiotics, antimicrobial peptides (AMP), gut bacteriophages, fecal microbiota transplantation (FMT), and selected nutraceutical and dietary interventions. While some approaches show promising biological or clinical signals, the strength of evidence varies considerably, ranging from in vitro and animal studies to randomized clinical trials and meta-analyses. Antibiotic therapies targeting intestinal pathogens have shown heterogeneous results, suggesting the need for pathogen-guided and intracellularly active antimicrobial strategies. Novel approaches, including AIEC-specific phages and AMP-based interventions, represent promising microbiome-sparing alternatives capable of selectively modulating disease-associated microorganisms. Furthermore, FMT and nutraceuticals may contribute to restoring microbial balance and strengthening intestinal homeostasis, although their efficacy requires further validation in controlled clinical trials. Overall, these strategies support a transition toward precision medicine approaches integrating microbial profiling, host immune characterization, and targeted antimicrobial interventions to improve therapeutic outcomes in CD.
SN  - 2079-6382
ER  -