Letter to the Editor: Probiotics counteract polyethylene glycol bowel preparation dysbiosis and infection risk

Abstract

Polyethylene glycol (PEG) bowel preparation, though widely used, can significantly disrupt gut microbiota composition. Kou et al recently published study in the World Journal of Gastroenterology, which demonstrated that PEG-treated mice challenged with Citrobacter rodentium exhibit higher pathogen loads, elevated virulence gene expression, and worsened colitis, mediated by microbiota dysbiosis. Importantly, Lactobacillus acidophilus supplementation restored microbial balance and mitigated infection severity, suggesting PEG-induced loss of colonization resistance exposes a 14-day infection window. This paradigm aligns with a rare human case of septic shock after PEG bowel preparation, highlighting potential opportunistic infection risk. Probiotic Lactobacillus strengthen the epithelial barrier and modulate immunity, and clinical trials support their efficacy and safety in gastrointestinal contexts. We discuss the translational significance of these findings and advocate microbiota-protective strategies (probiotic supplementation, optimal timing of endoscopy, and dietary adjustments) during bowel preparation.

Key Words: Polyethylene glycol; Bowel preparation; Dysbiosis; Citrobacter rodentium; Probiotics; Colonoscopy; Infection risk

Core Tip: Polyethylene glycol bowel preparation can transiently disrupt gut microbiota and weaken colonization resistance, potentially increasing susceptibility to enteric infections. Kou et al provide mechanistic evidence that polyethylene glycol creates a 14-day vulnerability window in which Citrobacter rodentium colonization, virulence, and colitis severity are amplified in a microbiota-dependent manner. Importantly, Lactobacillus acidophilus supplementation restores microbial balance and reduces infection severity, supporting microbiota-protective strategies. These findings, together with real-world data showing non-negligible post-colonoscopy infection visits, argue for risk stratification and microbiota-sparing adjuncts in high-risk patients.

TO THE EDITOR

Colonoscopy is the most effective method for colorectal cancer prevention, significantly reducing mortality via polyp removal. However, high-quality bowel preparation is a prerequisite. Inadequate cleansing leads to missed lesions, prolonged procedures, repeat examinations, and increased medical burden. Polyethylene glycol (PEG) is a non-absorbable polymer that cleanses the bowel via osmotic action and is widely preferred, especially for high-risk patients, due to its superior safety in maintaining electrolyte balance. However, mounting evidence indicates they profoundly alter colonic microbial ecology[1-3]. Multiple studies report that PEG bowel preparation significantly reduces microbial diversity and the abundance of beneficial bacteria like Lactobacillaceae. Conversely, it increases the abundance of facultative anaerobes such as Proteobacteria[1-3]. Mechanistically, rapid evacuation of luminal contents and high osmolarity deplete nutrients and mucus, shifting the niche toward oxygen-tolerant pathogens[1]. These perturbations are usually transient. Most individuals’ microbiota rebound to baseline within 2 weeks to 4 weeks[1]. However, in susceptible individuals, dysbiosis may transiently weaken colonization resistance against exogenous pathogens.

PEG AND INFECTION SUSCEPTIBILITY

Clinically, gut dysbiosis can compromise colonization resistance, potentially raising infection risk. Traditional thinking has long held that infections after colonoscopy are exceedingly rare. However, current evidence relies largely on retrospective, observational big-data studies. While the absolute incidence remains low, reported at approximately 1.1% for screening and 1.6‰ for diagnostic procedures, the immense global volume of colonoscopies makes this a clinically relevant concern that may be underestimated[4]. Such events commonly present as gastrointestinal infections, and frequently involve enteric commensals/opportunistic pathogens such as Escherichia coli (E. coli) and Klebsiella (as well as Clostridioides difficile in some cases)[4]. Severe infections after PEG bowel preparation have also been reported. A healthy 33-year-old developed septic shock soon after colonoscopy with PEG bowel preparation, leading authors to suspect an opportunistic infection facilitated by the preparation[5]. Moreover, preparation before colorectal surgery did not reduce intraoperative bacterial contamination, suggesting limited benefit for pathogen clearance[5]. Together, this implies that standard PEG bowel preparation may transiently weaken mucosal defenses, especially in high-risk hosts, by wiping out protective gut microbes.

ANALYSIS OF INSIGHTS

The recent study published in the World Journal of Gastroenterology by Kou et al[6] directly tests this concept. They pre-treated mice with PEG and then challenged them with Citrobacter rodentium, a murine pathogen that models human enteropathogenic E. coli/enterohemorrhagic E. coli[7]. PEG-treated mice exhibited markedly higher C. rodentium burdens, elevated expression of bacterial virulence genes, and more severe colonic inflammation, with an extended infection window of two weeks[6]. Fecal metagenomics and co-housing experiments confirmed these effects were microbiota-dependent[6]. However, Qi et al[8] showed that when PEG is present during infection, it can reduce C. rodentium attachment. The literature appears contradictory on whether PEG is protective or harmful. A dichotomy emerges based on the timing of exposure. As shown by Qi et al[8], PEG can downregulate host epithelial receptors like β₁-integrin and block bacterial attachment, offering a transient shielding effect during the active lavage phase. However, this benefit is short-lived as the solution is rapidly evacuated. The clinical concern, therefore, shifts to the subsequent delayed risk phase: A 14-day window where the protective PEG coating is gone, but the commensal colonization resistance has not yet recovered. We should recognize that the immediate mechanical clearance does not equate to prolonged biological defense. Critically, mice given Lactobacillus acidophilus (L. acidophilus) before infection had restored microbial balance and resisted PEG-associated susceptibility, demonstrating L. acidophilus protective role. Kou et al[6] conclude that PEG increases intestinal susceptibility to infection in a microbiota-dependent manner, highlighting the therapeutic potential of L. acidophilus (Figure 1).

Figure 1 Schematic diagram illustrating the polyethylene glycol bowel preparation-induced infection window and the protective efficacy of probiotics. Created using the BioRender. The illustration contrasts the biological impact of standard bowel preparation against a probiotic-assisted protocol. The rapid evacuation of luminal content during standard polyethylene glycol preparation leads to dysbiosis and barrier defects, creating a 14-day vulnerability window characterized by impaired colonization resistance and increased pathogen susceptibility. Intervention with Lactobacillus acidophilus restores microbial homeostasis, reinforces the mucosal barrier and prevents pathogen invasion. PEG: Polyethylene glycol; C. difficile: Clostridioides difficile; E. coli: Escherichia coli; L. acidophilus: Lactobacillus acidophilus.

PROBIOTIC MECHANISMS AND EVIDENCE

L. acidophilus has been proven to enhance intestinal barrier function and modulate immunity. Al-Sadi et al[9] identified an L. acidophilus strain that rapidly enhanced epithelial tight-junction integrity via toll-like receptor 2 signaling, and protected mice from dextran sulfate sodium-induced colitis. A key mechanism underlying infectious diarrhea is the downregulation of apical ion exchangers, such as Na⁺/H⁺ exchanger 3 and Cl^-/HCO₃^- exchanger, by inflammatory cytokines like tumor necrosis factor-α and interferon-γ. This downregulation leads to electrolyte malabsorption[10]. L. acidophilus could reverse the C. rodentium-induced suppression of these transporters, thereby restoring intestinal water absorption and alleviating diarrheal symptoms[10]. Previous studies indicate that these L. acidophilus-primed dendritic cells are capable of inducing the differentiation of regulatory T cells and promoting the secretion of specific IgA by B cells[11]. Similarly, orally administered L. acidophilus (strain BIO5768) attenuated C. rodentium-induced colitis in mice, partly through interleukin-17-dependent innate defense and group 3 innate lymphoid cells activation[12]. Beyond L. acidophilus, other probiotics (e.g., L. reuteri, L. rhamnosus) exhibit gut-protective effects, and multi-strain regimens often outperform single strains. Clinical trials have established safety and some efficacy of Lactobacillus in gastrointestinal disorders. L. acidophilus (LA85) could reduce diarrhea duration and improved quality-of-life without adverse events in patients with antibiotic-associated diarrhea[13]. A recent review concluded that targeted probiotic use is supported by sufficient efficacy and safety evidence for certain indications (e.g. maintaining gut health during antibiotics)[14].

TRANSLATIONAL PERSPECTIVE

Interpreting these results in humans requires caution. C. rodentium is a valuable model of infections, sharing similar pathogenesis with human enteropathogenic E. coli/enterohemorrhagic E. coli, fundamental differences in physiology and microbiota composition between mice and humans limit direct extrapolation[7]. Human PEG protocols and gut recovery dynamics also vary significantly. Clinically, the relevant pathogens might differ (e.g., Enterobacteriaceae, Clostridioides difficile). Therefore, findings from murine models must be validated in clinical settings. Nevertheless, in vivo studies still offer valuable insights, we must realize that aggressive lavage may strip away colonization resistance. Epidemiologic vigilance is warranted, especially for hospitalized or immunocompromised patients undergoing bowel prep.

CLINICAL IMPLICATIONS AND FUTURE DIRECTIONS

Kou et al’s work[6] prompts rethinking standard colonoscopy protocols, particularly the assumption that bowel preparation is a benign, “one-size-fits-all” step. While PEG bowel preparation-induced microbiota perturbations may be transient in healthy individuals, it could be clinically consequential in high-risk groups. Specifically, we define these vulnerable populations by indicators such as advanced age (> 65 years), active immunosuppressive therapy (e.g., chemotherapy, corticosteroids), and a history of antibiotic use within three months. Against this backdrop, we propose incorporating a brief microbiota risk assessment into the pre-procedure consultation. For patients with these risk factors, a microbiota-protective approach becomes highly relevant. Administering probiotics immediately post-preparation has been shown to mitigate gastrointestinal symptoms and aid microbial recovery[1]. Split-dose PEG and CO₂ insufflation could reduce dysbiosis, and clinicians might delay elective procedures when recent antibiotic use or dysbiosis is present. Dietary modulation (high-fiber intake or prebiotics) may accelerate microbiota rebound after lavage. Given that current human data are primarily retrospective, future research should prioritize prospective, longitudinal studies to correlate PEG bowel preparation-induced dysbiosis with clinical infection outcomes. Randomized controlled trials are indispensable to confirm whether specific probiotic strains, such as L. acidophilus, can safely and effectively restore colonization resistance in patients undergoing bowel preparation. But in the interim, risk stratification plus microbiota-sparing adjuncts offers a pragmatic path to reduce preventable infection risk during the vulnerable recovery window.