From Allies to Adversaries: Antibiotics and Their Influence on Gut Microbiome

The gut microbiome is a diverse microbial ecosystem comprising commensal bacteria that live in symbiosis with the host. The microbiome plays a fundamental role in overall health, including the maintenance of metabolic, immune, neurologic, and gastrointestinal (GI) homeostasis. Numerous factors may contribute to microbiome composition, including medications, age, lifestyle, diet, and environmental factors, and microbiota disturbances have been linked to a wide array of human diseases and have long-lasting, far-reaching consequences. The gut microbiome is dominated by 2 main phyla, Bacteroidetes and Firmicutes, which together account for approximately 90% of the microbial community, followed by Actinomycetota, Fusobacteriota, Proteobacteria, Verrucomicrobiota, and Cyanobacteriota.^1-3

Systemic antibiotic therapy leads to microbiome dysbiosis, characterized by decreased microbial diversity and abundance, reduced commensal species, excessive proliferation of pathogenic microbes, and selection for resistant species.^3,4 However, antibiotics differ regarding impact on the microbiome. Broad-spectrum antibiotics are thought to disrupt the microbiota to a greater extent than narrow-spectrum agents; however, the degree of impact is multifaceted and influenced by each antibiotic's spectrum of activity and pharmacokinetic properties.^2,3 Antibiotics known to eradicate beneficial bacteria (eg, Actinomycetota, Bifidobacteriales, Lactobacillus spp.) and increase the abundance of Enterococcus spp. and Enterobacteriaceae are associated with the most significant long-lasting microbiome disruptions.^2,5

Antibiotic Classes and Microbiome Impact

Antibiotics with the greatest impact include clindamycin, fluoroquinolones, macrolides, carbapenems, and broad-spectrum β-lactams.^2,6,7 Clindamycin is among the most disruptive due to its significant reduction in anaerobic commensals (Bacteroides spp.) and its increased risk of Clostridioides difficile infection.^3,6,7 Tetracyclines, sulfonamides, narrow-spectrum penicillins, and aminoglycosides are associated with a comparatively lower disruption impact.^3,6,7 Although evidence is variable, significant alterations to gut microbial composition may persist for up to 2 years post treatment.^2,6 Emerging evidence suggests that certain agents, including clindamycin, fluoroquinolones, and flucloxacillin, may be associated with gut microbial alterations lasting from 4 to 8 years.⁶

Antibiotic utilization remains widespread. According to the Centers for Disease Control and Prevention’s 2024 outpatient prescription report, 255.9 million oral antibiotic prescriptions were dispensed in 2024. This represents 752 prescriptions per 1000 persons in the United States population, translating to 75% of the population being treated with at least 1 antibiotic each year, without considering intravenous antibiotics.⁸ Mitigating the impact of antibiotics is paramount and may be accomplished using a 2-tiered strategy. First, antibiotic stewardship is necessary, including optimizing and narrowing therapy and selecting agents to minimize collateral damage with lower disruption impact.^3,6,7 Second, one should support microbiome recovery by restoring the natural balance of microorganisms within the human GI tract.

Foods and Improving the Microbiome

Prebiotic fibers, fermented foods, and probiotics are dietary compounds that may improve gut microbiome composition.^9-11 Prebiotic fibers pass through the GI tract undigested, are selectively fermented, and promote the growth of beneficial bacteria such as Bifidobacterium and Lactobacillus, thereby enhancing microbial diversity.⁹ Fermented foods transiently colonize the gut with diverse microbes and facilitate favorable microbial diversity and resilience.¹⁰ In contrast, probiotics deliver specific, characterized, clinically validated strains of microbial communities that are supported by clinical evidence for their role in microbiome modulation.¹¹ Although a deep-dive exploration of the interrelationships between pharmaceuticals, gut microbiome, and probiotics or prebiotics is beyond the scope of this article, 2 recent scientific publications reviewing targeted probiotics, prebiotics, and dietary modulation may fill this niche.^12,13

The gut microbiome is a diverse and complex community essential to human health. Antimicrobial-associated disruption is variable and multifaceted. Antimicrobial stewardship and utilization of prebiotic fiber, fermented foods, and probiotics are recommended strategies to minimize microbiome disruption and reestablish a healthy and diverse microbial gut population.

The Society of Infectious Diseases Pharmacists (SIDP) is an association of pharmacists and other allied health care professionals who are committed to promoting the appropriate use of antimicrobial agents and supporting practice, teaching, and research in infectious diseases. We aim to advance infectious diseases pharmacy and lead antimicrobial stewardship in order to optimize the care of patients. To learn more about SIDP, visit sidp.org.

References

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2. Montelin H. Antibiotic-Induced Damage on the Intestinal Microbiota and Treatment of Urinary Tract Infections Caused by ESBL- and Non-ESBL-Producing Bacteria. Acta Universitatis Upsaliensis; 2024.

3. Wurm J, Curtis N, Zimmermann P. The effect of antibiotics on the intestinal microbiota in children - a systematic review. Front Allergy. 2024;5:1458688. doi:10.3389/falgy.2024.1458688

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5. Peto L, Fawcett N, Kamfose MM, et al. The impact of different antimicrobial exposures on the gut microbiome in the ARMORD observational study. Elife. 2025;13:RP97751. doi:10.7554/eLife.97751

6. Baldanzi G, Larsson A, Sayols-Baixeras S, et al. Antibiotic use and gut microbiome composition links from individual-level prescription data of 14,979 individuals. Nat Med. 2026;32(4):1351-1361. doi:10.1038/s41591-026-04284-y

7. Patangia DV, Ryan CA, Dempsey E, Ross RP, Stanton C. Impact of antibiotics on the human microbiome and consequences for host health. Microbiologyopen. 2022;11(1):e1260. doi:10.1002/mbo3.1260

8. Outpatient Antibiotic Prescriptions United States, 2024. Centers for Disease Control and Prevention. 2024. Accessed April 27, 2026. https://www.cdc.gov/antibiotic-use/media/pdfs/2024-Annual-Report-508.pdf

9. Monteiro CRAV, Bogea EG, Campos CDL, et al. Prebiotics and gut health: mechanisms, clinical evidence, and future directions. Nutrients. 2026;18(3):372. doi:10.3390/nu18030372

10. Iqbal B, Alabbosh KF, Raheem A, Ullah I, Khan AR, Memon MS. Microbial transformation: the role of fermentation in advancing nutritional quality and human health. Arch Microbiol. 2025;207(9):228. doi:10.1007/s00203-025-04435-8

11. Chandrasekaran P, Weiskirchen S, Weiskirchen R. Effects of probiotics on gut microbiota: an overview. Int J Mol Sci. 2024;25(11):6022. doi:10.3390/ijms25116022

12. Li Z, Samui S, Liu J, et al. Gut microbiome and metabolic health: mechanisms and precision interventions. Gut Microbes. 2026;18(1):2644677. doi:10.1080/19490976.2026.2644677

13. Al-Btoosh S, Donnelly RF, Kelly SA. Microbes and medicines: interrelationships between pharmaceuticals and the gut. Gut Microbes. 2026;18(1):2604867. doi:10.1080/19490976.2025.2604867