Non‑tuberculous mycobacteria (NTM) have emerged as a growing clinical problem in recent decades. The review emphasizes the complexity of treating NTM infections due to intrinsic and acquired antimicrobial resistance, the ability of many NTM species to form biofilms, and the prolonged and often toxic treatment regimens required for disease control. These features have driven interest in alternative or adjunctive approaches, including therapies derived from natural products.
The authors conducted a systematic search of major biomedical databases — PubMed, Scopus, Web of Science, Embase, the Cochrane Library, and Google Scholar — for relevant publications up to December 2025. The review included laboratory (in vitro) studies, in vivo animal models, and any available clinical trials that assessed the antimycobacterial actions of natural products. Methodological quality and risk of bias were appraised using ToxRTool for toxicology-related studies and SYRCLE for animal experiments.
A diverse set of natural agents was assessed across the included studies. These comprised essential oils, isolated phytochemicals, and probiotics. The selected literature examined effects on several clinically relevant NTM species, most notably Mycobacterium avium and Mycobacterium abscessus complexes. Representative agents named in the review included Juniperus communis essential oil, Helichrysum italicum essential oil, berberine combinations, and fractions derived from citrus oils.
The preponderance of evidence in the review comes from laboratory‑based investigations (15 of 19 selected studies). Multiple natural products demonstrated measurable antimycobacterial activity in vitro. Important observations included:
Several essential oils and phytochemicals showed direct inhibitory activity against NTM strains tested in vitro.
Some compounds exhibited synergistic or additive effects when combined with conventional antimycobacterial agents, suggesting potential as adjuncts to existing drug regimens.
Disruption of biofilm formation was proposed as one mechanism through which certain natural products exerted activity, which is relevant given the role of biofilms in chronicity and drug tolerance.
The review highlights these in vitro signals as promising but emphasizes that laboratory efficacy does not equate to clinical effectiveness without further validation.
Fewer animal and clinical studies were available, and their findings were less consistent. Reported outcomes included occasional immunomodulatory effects, imaging stability in limited cases, and some reductions in bacterial load; however, substantial and reproducible clearance of infection was rarely documented. The authors caution that evidence from animal models and human studies is insufficient to support clinical implementation of these natural products for NTM treatment at present.
Using established tools (ToxRTool and SYRCLE), the review assessed the methodological rigor and potential biases of included studies. The overall quality of current research was described as inconsistent. Many laboratory studies lacked the level of validation and standardization required to translate findings into clinical practice. Animal and clinical experiments were scarce and variable in design, limiting confidence in reported effects and generalizability.
The systematic review concludes that natural products — including essential oils, phytochemicals, and probiotics — show promise as antimycobacterial agents in vitro and may have adjunctive roles by enhancing conventional drug activity or interfering with biofilms. Nonetheless, clinical success remains limited based on currently available evidence. Key limitations identified include the small number of non‑laboratory studies, heterogeneity of experimental methods, and variable study quality. The authors note that significant clinical benefit has not been established and that safety, dosing, and interaction profiles require clarification.
The authors call for rigorously designed experimental and clinical studies to validate the therapeutic role of natural products in NTM management. Specifically, well‑controlled preclinical work that standardizes assays and elucidates mechanisms, followed by properly powered animal and human trials, will be necessary to determine efficacy, optimal dosing, safety, and potential for integration as adjuncts to conventional therapies. Until such data are available, natural products should be considered investigational in the context of NTM infection.