A Mechanistic Approach to Replacing Antibiotics with Natural Products in the Treatment of Bacterial Diarrhea

Abstract

Natural products have emerged as potential alternatives to antibiotics in the treatment of bacterial diarrhea, due to their multi-targeting effects, low potential for inducing resistance, and favorable safety profiles. Currently, the search for natural product-based therapies has become an emerging focus in medical research. This growing interest is driven by the increasing awareness that the widespread and irrational use of antibiotics has contributed to the alarming rise in antibiotic-resistant bacterial strains, which in turn diminishes the efficacy of conventional drugs. Among these concerns, the limitations of antibiotics in managing bacterial diarrhea and the potential mechanisms by which natural products exert therapeutic effects are the main focus of this paper. Natural products, containing a wide array of bioactive compounds, can not only directly inhibit the growth of pathogenic bacteria, disrupt bacterial membrane synthesis, and reduce toxin production, but also modulate inflammatory responses, enhance immune function, repair intestinal barriers, and restore gut microbial ecology-highlighting their systemic and multi-targeted therapeutic potential. Therefore, this paper will elaborate on how natural products combat bacterial diarrhea from three aspects: the pathogen and pathogenesis of bacterial diarrhea, natural product-based therapeutic studies, and the underlying mechanisms of action, thereby proposing natural products as viable alternatives to antibiotics.

Keywords: antibiotic mechanism of action; antibiotics; diarrhea-causing bacteria; natural product mechanism of action; natural products; pathogenesis.

Figure 1

Pathogenesis of bacterial diarrhea due to intestinal flora dysbiosis. Note: ‘+’ indicates promotion or activation; ‘−’ indicates inhibition or suppression.

Figure 2

Four types of antibiotic compounds’ chemical structures. Quinolone antibiotics—represented by ciprofloxacin, a fluoroquinolone that inhibits DNA gyrase and topoisomerase IV, thereby disrupting bacterial DNA replication. β-Lactam antibiotics—represented by amoxicillin, a penicillin-type agent that targets penicillin-binding proteins and inhibits bacterial cell wall synthesis. Aminoglycoside antibiotics—represented by neomycin, which binds to the 30S ribosomal subunit and causes mistranslation of bacterial proteins. Macrolide antibiotics—represented by erythromycin, which binds to the 50S ribosomal subunit and inhibits peptide chain elongation.

Figure 3

Mechanisms by which natural products treat bacterial diarrhea by interfering with membrane structure, inhibiting membrane lipid synthesis, inducing changes in membrane permeability and membrane dysfunction. Note: ‘+’ indicates promotion or activation; ‘−’ indicates inhibition or suppression.

Figure 4

Mechanisms by which natural products treat bacterial diarrhea by disrupting the synthesis of bacterial genetic material and modulating virulence factor expression pathways.

Figure 5

Mechanisms of natural products for the treatment of bacterial diarrhea by inhibiting the synthesis of T3SS and toxins such as LT and ST, toxin secretion, and toxin functions. Note: ‘+’ indicates promotion or activation; ‘−’ indicates inhibition or suppression.

Figure 6

Mechanisms by which natural products treat bacterial diarrhea by protecting intestinal tissues.

Figure 7

Mechanisms of natural products in the treatment of bacterial diarrhea through immunomodulation. Note: ‘+’ indicates promotion or activation; ‘−’ indicates inhibition or suppression.