Multiple studies indicate that antibiotics disrupt the gut microbiome, which plays a vital role in regulating the immune system and supporting immune-based therapies, but direct evidence that antibiotics globally weaken the human immune system outside of microbiome-mediated mechanisms is limited to partial findings.
Antimicrobial resistance (AMR) is one of the most pressing threats to global health system. The human gut harbors a complex microbial ecosystem coordinated through mechanisms of metabolic interdependence. The gut microbiota plays a vital role in normal growth and physiological processes of the human body. It serves both as a target of antibiotic-mediated disruption and as a reservoir for the propagation of antimicrobial resistance genes. Although antibiotics remain indispensable for the treatment of bacterial infections, their broad ecological impact on the gut microbiota can undermine the microbial balance that protects the host against pathogen invasion and metabolic dysfunction. The gut microbiome also functions as a reservoir of antimicrobial resistance genes collectively termed the "resistome," which can be mobilised and transferred between commensal and pathogenic bacteria via horizontal gene transfer mechanisms such as conjugation, transformation, and transduction. This review examines the composition and functions of the human gut microbiota, the mechanism of antibiotic-induced gut dysbiosis, and the role of host factors like age, genetics, diet and immune status, on microbiome dynamics and AMR development. We further evaluate emerging methods for resistome characterisation, which include PCR, next-generation sequencing, functional metagenomics and artificial intelligence-driven tools. Finally, we discuss microbiome-targeted therapeutic strategies such as faecal microbiota transplantation (FMT), phage therapy, CRISPR-based therapies, and antimicrobial peptides for combating AMR and restoring gut microbial homeostasis. Overall, this review highlights that maintaining and re-establishing the integrity of the gut microbiome should be considered a fundamental component of antimicrobial stewardship strategies aimed at controlling AMR worldwide.
The gut microbiome also functions as a reservoir of antimicrobial resistance genes collectively termed the “resistome,” which can be mobilised and transferred between commensal and pathogenic bacteria via horizontal gene transfer mechanisms such as conjugation, transformation, and transduction. This review examines the composition and functions of the human gut microbiota, the mechanism of antibiotic-induced gut dysbiosis, and the role of host factors like age, genetics, diet and immune status, on microbiome dynamics and AMR development.
Simultaneously, the extensive use of antibiotics in livestock for growth promotion and disease prevention contributes to the emergence of resistant bacteria. These bacteria can spread to humans through the food chain, direct contact, and environmental exposure ( Marshall and Levy, 2011 ). Inside the human body, the gastrointestinal tract harbors the largest and most complicated microbial ecosystem, known as the gut microbiome. This diverse community of microorganisms plays an essential role in the host health by promoting digestion and metabolism, improving and regulating the immune system, and protecting against invading pathogens ( Sommer and Bäckhed, 2013 ).
Despite increasing recognition of the gut microbiome’s role in AMR, the long-term consequences of antibiotic-induced dysbiosis and the influence of host-related factors such as diet, age, immune status, hospitalisation, and geographic context remain incompletely understood ( Yatsunenko et al., 2012 ; David et al., 2014 ). Moreover, current clinical approaches often overlook microbiome preservation and restoration as essential component of antimicrobial stewardship ( Langdon et al., 2016 ).
Illustration showing the difference between gut eubiosis and dysbiosis, linking antibiotic use, reduced microbial diversity, pathogen expansion, impaired gut barrier, immune cell dysfunction, and decreased production of beneficial short-chain fatty acids from dietary fiber. 4.2 Impact of antibiotics on gut microbiota The magnitude and duration of antibiotic-induced microbiota disruption largely depend on the spectrum of activity, duration of exposure, and pharmacokinetic properties of the antibiotic.
7 Host factors influencing microbiome-antibiotic-AMR outcomes 7.1 Age and developmental stage The host age at the time of antibiotic exposure profoundly shapes the severity of microbiome disruption, the degree of resistome enrichment, and the capacity for community recovery reflecting fundamental differences in microbiome composition, immune maturation, and ecological stability across the human lifespan ( Bradley and Haran, 2024 ).
In sub-Saharan Africa and parts of Asia, fewer than 30% of healthcare centres have regular access to cultural and antimicrobial susceptibility testing facilities, primarily due to a shortage of reagents, lack of staff, infrastructure constraints and weak quality systems ( Elbehiry et al., 2025a ). This display is not merely logistical; it creates critical blind spots in global resistome maps, as AMR hotspots in LMICs driven by high antibiotics consumption, poor sanitation and dense animal-human interfaces remain poorly characterised by sequence-based surveillance.
10.5 Antimicrobial peptides Antimicrobial peptides (AMPs) are emerging as promising microbiome-targeted therapeutics with potential applications in gut-brain axis disorders ( Sharma et al., 2025 ). AMPs are small cationic peptides naturally produced by animals, plants, and microorganisms as part of the innate immune defence system. Owing to their broad-spectrum antimicrobial activity, immunomodulatory properties, and lower propensity for resistance development, they are increasingly being explored as alternatives to conventional antibiotics ( Mba and Nweze, 2022 ). Several AMPs are currently under clinical evaluation for infectious and inflammatory diseases ( Dijksteel et al., 2021 ).
Recent studies have demonstrated that CRISPR-Cas equipped bacteriophages can specifically target and cleave resistance determinants, thereby restoring bacterial susceptibility to conventional
Antibiotics are among the most commonly used anti-infective agents in modern medicine. However, their long-term effects on the gut microbiome have attracted increasing attention. Epidemiological studies and animal experiments in recent years suggest that antibiotic exposure can disrupt the structure and function of the gut microbiota, thereby affecting host energy metabolism, fat deposition, and immune homeostasis. Such disruptions may contribute to the development of obesity and related metabolic phenotypes. Different classes of antibiotics exert markedly distinct effects on the gut microbiota. Broad-spectrum antibiotics such as macrolides, lincosamides, and fluoroquinolones often induce more pronounced and prolonged microbial alterations, whereas the effects of certain β-lactam antibiotics appear relatively transient. Antibiotic-induced gut dysbiosis can influence host metabolism through multiple mechanisms, including reduced short-chain fatty acid production, disrupted bile acid metabolism, impaired intestinal barrier function, and chronic low-grade inflammation. These alterations may promote fat accumulation, insulin resistance, and disruption of immune homeostasis. Early-life antibiotic exposure occurs during a critical developmental window for gut microbiota maturation and may exert more profound effects on long-term metabolic health. Recent advances in multi-omics technologies have further illuminated the complex interaction network among antibiotics, the microbiome, and host metabolism. Microecological intervention strategies, such as probiotics and synbiotics, show potential for improving metabolic abnormalities associated with antibiotic-induced dysbiosis. However, their efficacy is strain-specific, and the overall effect size remains limited. This review summarizes current research progress on how antibiotic exposure influences obesity and metabolic phenotypes through the gut microbiota, outlines the underlying mechanisms, and discusses potential applicat
However, their long-term effects on the gut microbiome have attracted increasing attention. Epidemiological studies and animal experiments in recent years suggest that antibiotic exposure can disrupt the structure and function of the gut microbiota, thereby affecting host energy metabolism, fat deposition, and immune homeostasis. Such disruptions may contribute to the development of obesity and related metabolic phenotypes. Different classes of antibiotics exert markedly distinct effects on the gut microbiota.
In mouse models, subtherapeutic (low-dose) antibiotic administration has been consistently shown to increase fat mass. Cho et al. (2012) confirmed that early exposure to low-dose penicillin, vancomycin, or chlortetracycline led to increased fat mass and altered short-chain fatty acids (SCFAs) production without significantly reducing total microbial density. Cox et al. (2014) further showed that low-dose penicillin exposure during pregnancy or weaning induced increased fat mass, impaired immune development, and persistent metabolic alterations.
Illustration showing the impact of antibiotics on gut microbiota, leading to decreased short-chain fatty acids (SCFAs) and microbial imbalance, resulting in intestinal barrier disruption, increased lipopolysaccharides (LPS) in circulation, and subsequent fat accumulation, insulin resistance, systemic inflammation, and immune system destruction. However, some reports indicate that antibiotic exposure has minimal or even no significant long-term effects on metabolism, a phenomenon that appears to be more pronounced in certain populations or under specific antibiotic usage scenarios ( Benitez et al., 2025 ).
These findings suggest that antibiotic-induced alterations in microbiota composition may impair the gut's ability to metabolize dietary carbohydrates, leading to accumulation of monosaccharides in the intestinal lumen and subsequent disruption of insulin signaling pathways. 3.3 Systemic inflammation and disruption of immune homeostasis Antibiotic-induced disruption of local and systemic immune homeostasis in the gut is associated with compromised intestinal barrier integrity and diminished immunoregulatory signaling from the microbiota.
Antibiotic exposure reduces the production of SCFAs, such as butyrate, which serves as the primary energy source for colonic epithelial cells and is critical for maintaining tight junctions between epithelial cells. Decreased butyrate levels weaken intestinal epithelial barrier function, leading to “leaky gut” ( Takeuchi et al., 2023 ). Concurrently, antibiotic exposure may alter microbial composition and increase the relative abundance of potentially harmful bacteria.
Furthermore, a study indicates that antibiotic-associated dysbiosis may be accompanied by reduced numbers or impaired function of colonic regulatory T cells (Tregs) ( Zhang et al., 2021 ). Tregs are crucial for maintaining immune tolerance and suppressing excessive inflammatory responses. Their depletion further diminishes immune tolerance, leading to immune dysregulation. This immune imbalance can exacerbate systemic inflammatory responses while simultaneously increasing the risk of obesity, diabetes, and other metabolic disorders. Cox et al.
Early antibiotic exposure may further influence metabolic health by altering immune system function. Lamont et al. (2020) examined the relationship between antibiotic use during pregnancy, delivery, and the neonatal period and the development of childhood inflammatory and metabolic diseases. Their findings indicated significant associations between antibiotic exposure and childhood allergic diseases, asthma, and obesity, with the strongest associations observed between prenatal antibiotic exposure and the risk of childhood obesity and allergic diseases.
Therefore, future research should further explore strategies to optimize probiotic use, particularly in specific populations. 6 Conclusion Antibiotic exposure can trigger a series of
The immune system plays a key role in cancer suppression. Immunotherapy is widely used as a treatment method in patients with various types of cancer. Immune checkpoint blockade using antibodies, such as anti-PD-1, anti-PD-L1, and anti-CTLA-4, is currently gaining popularity. A systematic literature search was executed, and all available data was summarized. This review shows that specific dietary patterns (such as, e.g., animal-based, vegetarian, or Mediterranean diet) alter the gut microbiome’s composition. An appropriate intestinal microbiota structure might modulate the function of human immune system, which affects the bodily anti-cancer response. This paper shows also that specific bacteria species inhabiting the gastrointestinal tract can have a beneficial influence on the efficacy of immunotherapy. Antibiotics weaken gut bacteria and worsen the immune checkpoint blockers’ efficacy, whereas a faecal microbiota transplant or probiotics supplementation may help restore bacterial balance in the intestine. Other factors (like vitamins, glucose, or BMI) change the cancer treatment response, as well. This review demonstrates that there is a strong association between one’s diet, gut microbiome composition, and the outcome of immunotherapy. However, further investigation on this subject is required.
This review shows that specific dietary patterns (such as, e.g., animal-based, vegetarian, or Mediterranean diet) alter the gut microbiome’s composition. An appropriate intestinal microbiota structure might modulate the function of human immune system, which affects the bodily anti-cancer response. This paper shows also that specific bacteria species inhabiting the gastrointestinal tract can have a beneficial influence on the efficacy of immunotherapy. Antibiotics weaken gut bacteria and worsen the immune checkpoint blockers’ efficacy, whereas a faecal microbiota transplant or probiotics supplementation may help restore bacterial balance in the intestine.
human intestinal microbiota faecal microbiota transplant immunotherapy immune checkpoint blockade nutrition diet pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pmc-license-ref CC BY 1. Introduction According to the current knowledge, the immune system plays an extremely important role in the pathogenesis of cancer [ 1 ].
The immune system can prevent tumor formation through the elimination of oncogenic viruses and inflammation-causing pathogens. It can also fight cancer development through a tumor immune surveillance, which is based on recognizing precancerous or cancerous cells and removing them before they cause any damage [ 2 ]. According to Sir Frank Macfarlane Burnet, the neoantigens on tumor cells can trigger an immune response. After the presentation of the tumor antigens, specific effector and memory cells are produced, in order to fight the tumor cells
The most important ones include the upregulation of checkpoint receptor ligands, which results in the reduction of the number of tumor infiltrating lymphocytes (TIL), the production of soluble immunosuppressive factors (IL-10, TGF-beta), the downregulation of elements responsible for antigen presentation, and tumor infiltration by suppressor immune cells (regulatory T cells, Treg) [ 8 ]. Immunotherapy is a technique which can suppress, strengthen, or induct the immune system. It can be used to treat many diseases, including cancer.
It includes bacteria, archaea, viruses, fungi, and protozoans [ 16 ], and is made by up to a 1000 species [ 17 , 18 ]. It plays a significant role in human health, participates in providing nutrients and vitamins, protects the body from pathogens, and modulates the function of the immune system [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. It is also said to affect cancer patients’ response to immunotherapy [ 21 , 25 , 26 , 27 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ] and affect mental health [ 15 ]. 4. What Is the Composition of Gut Microbiota? When talking about gut microbiota, three “enterotypes” are described.
hirae induces Th17 cells’ response and has the potential to increase the cytotoxic T cells/Treg cells ratio [ 65 ]. The adaptive immune system can be activated by the nucleotide-binding oligomerization domain 2 (NOD2). NOD2 is a component of the bacterial cell wall. This component facilitates boosting the production of α-defensin or other regulatory particles, such as IFN [ 75 ].
The gut bacteria translocate to the mesenteric lymph nodes and enter the peripheral circulation, which might lead to local inflammation or the inflammation of the whole organism [ 69 ]. Especially in older people, high levels of gram-negative bacteria in the gut are often responsible for chronic inflammation [ 76 ]. In turn, dysbiosis caused by antibiotics or an incorrect diet leads to the inactivity of the immune system and the development of various diseases. 8. The Impact of Microbiome on the Efficacy of the Immunotherapy Data shows that gut microbiota has a strong influence on the efficacy of cancer immunotherapy, chemotherapy, and radiotherapy [ 77 ].
Patients without antibiotic treatment or with short-term exposure to antibiotics (<7 days) had longer overall survival and progression-free survival than patients with longer antibiotic exposure [ 83 ]. The influence of antibiotic administration 60 days before the treatment is not as strong as its influence within 30 days prior to the immune checkpoint blockade treatment [ 86 ]. It is caused by a decrease in the gut microbiome’s variety and richnes leading to lower pro-inflammatory cytokine production and less pronounced tumor necrosis [ 31 , 39 ].
Immunological dysregulation is the cause of many non-infectious human diseases such as autoimmunity, allergy and cancer. The gastrointestinal tract is the primary site of interaction between the host immune system and microorganisms, both symbiotic and pathogenic. In this Review we discuss findings indicating that developmental aspects of the adaptive immune system are influenced by bacterial colonization of the gut. We also highlight the molecular pathways that mediate host–symbiont interactions that regulate proper immune function. Finally, we present recent evidence to support that disturba
Abstract Background : Immune-checkpoint inhibitors (ICIs) have been approved as 1st line therapy and benefit patients with advanced cancer. However, still many patients fail to achieve the significant efficacy, a predictor for precise patient selection is needed. The aim of our study is to determine whether the administration of antibiotics before or at the beginning of ICIs treatment is a prognostic factor of progression-free survival (PFS) and overall survival (OS) in patients with advanced cancer. Methods : A systematic search in PubMed, Embase, Cochrane and Web of Science databases was conducted using the search terms antibiotic, PD-1, PD-L1, CTLA-4, combined with cancer, tumor, neoplasm, or carcinoma. Data extraction was performed independently. Hazard ratio (HR) for PFS and OS of antibiotics (+) group vs antibiotics (-) group were pooled according to random or fixed-effects models. HRs with 95% confidence intervals (CIs) for PFS and OS were pooled to obtain prognostic information and aggregate values. Results : Nine studies including 1163 patients were included in this meta-analysis. By PFS analysis, antibiotics administration was associated with a significantly increased risk of disease progression (HR, 1.76; 95% CI, 1.37-2.26; P < 0.01). By OS analysis, antibiotics uptake also showed an HR in favor of death (HR, 1.7; 95% CI, 1.40-2.07; P < 0.01). Conclusions : Based on the existing evidence, antibiotics administration is a prognostic factor for reduced PFS and OS in patients receiving ICIs treatment. The time interval between antibiotics administration and ICIs treatment should be considered.
Increasing researches reveal gut microbiota was associated with the development of tuberculosis (TB). How to prevent or reduce Mycobacterium tuberculosis colonization in the lungs is a key measure to prevent TB. However, the data on gut microbiota preventing Mycobacterium colonization in the lungs were scarce. Here, we established the clindamycin-inducing intestinal microbiome dysbiosis and fecal microbial transplantation models in mice to identify gut microbiota’s effect on Mycobacterium ’s colonization in the mouse lungs and explore its potential mechanisms. The results showed that clindamycin treatment altered the diversity and composition of the intestinal bacterial and fungal microbiome, weakened the trans-kingdom network interactions between bacteria and fungi, and induced gut microbiome dysbiosis in the mice. Gut microbiota dysbiosis increases intestinal permeability and enhances the susceptibility of Mycobacterium colonization in the lungs of mice. The potential mechanisms were gut microbiota dysbiosis altered the lung transcriptome and increased Nos2 expression through the ‘gut–lung axis’. Nos2 high expression disrupts the intracellular antimicrobial and anti-inflammatory
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