Ancient Chinese Herbal Medicine May Tame Chemotherapy’s Toxic Toll by Reshaping the Gut Microbiome

Chemotherapy saves lives, but it often exacts a brutal price. For patients with gastric cancer—one of the world’s most common and deadly malignancies—the drugs that attack tumors also ravage the immune system, the gastrointestinal tract, and the bone marrow. A new review published in Supportive Care in Cancer argues that the key to softening this collateral damage may lie not in the drugs themselves, but in the trillions of microbes that populate the human gut. Jialin Li of Qinghai University and Faxiang Ji of Qinghai University Affiliated Hospital systematically combed through SCI-indexed studies, many from recent years, to build a comprehensive picture of how traditional Chinese medicine (TCM) might ease chemotherapy-induced toxicities by restoring balance to a disrupted gut microbiota. Their conclusion is striking: a growing body of molecular and clinical evidence suggests that herbal polysaccharides, flavonoids, and classical formulations can act on the gut ecosystem in ways that measurably reduce inflammation, protect the intestinal lining, and support immune recovery during gastric cancer treatment.

The biological logic behind this approach begins with a phenomenon the authors call dysbiosis—a collapse of the gut’s normally diverse microbial community. Chemotherapy agents such as 5-fluorouracil, oxaliplatin, and cisplatin, the workhorses of gastric cancer regimens, do not discriminate neatly between tumor cells and the bacteria lining the intestine. The resulting microbial disruption damages the intestinal barrier, allowing bacterial components to leak into the bloodstream. Among these, lipopolysaccharide (LPS), a molecule embedded in the outer membrane of certain bacteria, is particularly consequential. Once LPS crosses a compromised gut wall, it binds to Toll-like receptor 4 (TLR4) on immune cells, triggering a signaling cascade through the transcription factor NF-κB and culminating in the activation of the NLRP3 inflammasome—a multiprotein molecular machine that ignites some of the body’s most potent inflammatory responses. The review identifies this LPS/TLR4/NF-κB/NLRP3 axis as a central driver of the systemic inflammation that underlies many chemotherapy side effects, from mucositis to immune dysfunction.

At the same time, chemotherapy starves the gut of one of its most valuable protective resources: short-chain fatty acids, or SCFAs. These small molecules—chiefly acetate, propionate, and butyrate—are produced by beneficial bacteria as they ferment dietary fiber. SCFAs are far more than metabolic waste; they act as signaling molecules and, remarkably, as inhibitors of histone deacetylases (HDACs), enzymes that control gene expression by chemically modifying chromatin. When SCFA levels fall, HDAC activity rises unchecked, anti-inflammatory gene programs are silenced, and the intestinal mucosa loses a critical shield against injury. Experimental work cited in the review shows that butyrate supplementation can prevent chemotherapy-induced gastrointestinal toxicity and microbial dysbiosis, while SCFA receptors such as GPR41, GPR43, and GPR109A on immune and epithelial cells mediate much of this protection. In other words, the difference between a tolerable chemotherapy course and a debilitating one may hinge, in part, on the metabolic output of a patient’s gut bacteria.

Against this mechanistic backdrop, the authors propose that TCM operates through what they term a structure–metabolite–immune framework. The idea is elegant in its simplicity: herbal compounds reshape the structure of the microbial community, the restructured community alters its production of metabolites, and those metabolites recalibrate the immune system. Restored microbial diversity means fewer LPS-producing pathogens and more SCFA-generating commensals. Lower LPS means less TLR4 activation; higher SCFAs means restored HDAC inhibition and calmer inflammatory signaling. The framework offers a unifying explanation for how wildly different herbal preparations—from complex multi-herb decoctions to single purified polysaccharides—can converge on similar protective outcomes. It also provides testable predictions: if the framework is correct, microbial sequencing and metabolite measurements should reveal consistent signatures in patients who respond well to TCM adjunct therapy.

The review catalogs a remarkable range of TCM components that fit this model. Polysaccharides from Astragalus membranaceus, a staple of Chinese herbal oncology, have been shown through multi-omics studies to protect against chemotherapeutic intestinal mucositis in animal models, and their structure–immunomodulation relationships are increasingly well mapped. Poria cocos polysaccharides exert a genuine prebiotic function, attenuating the adverse effects of 5-fluorouracil while improving its therapeutic outcome in mouse models of intestinal cancer. Polysaccharides from Atractylodes macrocephala protect against LPS-induced intestinal injury and appear to work partly by promoting gut bacterial production of tryptophan metabolites that activate the aryl hydrocarbon receptor, another key immunoregulatory pathway. On the flavonoid side, curcumin has been shown to suppress colorectal tumorigenesis partly by restoring gut microbiota and metabolites, while baicalin, derived from Scutellaria baicalensis, rebalances the regulatory T cell–Th17 axis and modulates SCFA profiles in models of colonic inflammation. Classical formulations such as Banxia Xiexin decoction and Shenling Baizhu powder have likewise been shown to reshape intestinal microbiota and SCFA metabolism in preclinical studies.

What elevates this review beyond a catalog of laboratory curiosities is its assessment of clinical evidence. The authors report that oral and injectable TCM formulations have accumulated moderate- to high-quality evidence for specific benefits in gastric cancer patients receiving chemotherapy. Shenqi Fuzheng injection (SFI), one of the most widely studied Chinese herbal injectables, has been the subject of multiple systematic reviews and meta-analyses showing improved immune function when combined with chemotherapy. Chinese herbal injections combined with SOX chemotherapy regimens—a common oxaliplatin plus S-1 protocol for advanced gastric cancer—have shown favorable effectiveness and safety profiles in Bayesian network meta-analyses. Oral preparations such as Shenqi Xiangyi granules have demonstrated benefits in advanced gastric cancer chemotherapy, and decoctions including Yipi Huayu and Zhipu Liujunzi have been associated in retrospective and propensity-matched studies with improved immune markers, favorable tumor marker trends, and reduced adverse reactions. The review also notes that these interventions appear to alleviate myelosuppression—the dangerous depletion of blood cell production in the bone marrow—and reduce gastrointestinal toxicities, two of the most clinically burdensome chemotherapy side effects.

The evidence is not uniformly strong, however, and the authors are candid about the gaps. External TCM therapies, including acupuncture and moxibustion, have generated some supportive data—a meta-analysis found benefits for gastrointestinal function and adverse events in gastric cancer patients after surgery and chemotherapy—but the overall quality of evidence for external approaches remains limited compared with oral and injectable formulations. Many of the most compelling mechanistic studies rely on animal models whose microbial and immune systems do not perfectly recapitulate human biology. Clinical trials are frequently small, single-center, and heterogeneous in their TCM preparations, dosing, and outcome measures, making it difficult to generalize. The review’s authors also point out that standard supportive care for chemotherapy toxicity—growth factors for neutropenia, antiemetic regimens for nausea—addresses symptoms rather than the underlying microbial and inflammatory mechanisms, leaving a genuine therapeutic vacuum that microbiota-targeted strategies could fill if properly validated.

Looking forward, the review charts several ambitious research frontiers. The authors highlight the STING signaling pathway—a DNA-sensing immune circuit with intimate connections to both inflammation and cell death—as an underexplored mechanistic link between microbial dysbiosis and chemotherapy toxicity. They similarly call for deeper investigation of the gut–brain axis, noting emerging evidence that chemotherapy-induced microbial disruption can exacerbate cancer-related fatigue through neuroimmune-endocrine signaling, and that interventions such as acupuncture and Lycium barbarum–probiotic combinations have shown promise in preclinical fatigue models by acting on this axis. Perhaps most consequentially, the authors advocate for large-scale randomized controlled trials and for the development of microbiota-based personalized TCM interventions—strategies in which a patient’s individual microbial profile would guide the selection of herbal therapy, much as tumor genomics guides targeted cancer drugs today. Such an approach would represent a genuine fusion of ancient pharmacopeia and modern precision medicine.

The implications extend well beyond gastric cancer. Dysbiosis has been implicated in chemotherapy-induced peripheral neuropathy, cardiotoxicity, and neurocognitive disorders, and microbial signatures of dysbiosis appear across gastrointestinal carcinogenesis. If the structure–metabolite–immune framework holds up under rigorous testing, microbiota modulation could become a standard pillar of supportive oncology care, alongside antiemetics and growth factors. For now, the review by Li and Ji stands as a careful synthesis of a rapidly maturing field—one that reframes chemotherapy toxicity not as an inevitable consequence of cancer treatment, but as a modifiable disorder of the gut ecosystem. The trillions of microbes that share our bodies, long overlooked in oncology, are emerging as both culprits and allies, and traditional Chinese medicine, whatever its ultimate clinical standing, has provided a rich and testable pharmacological toolkit for engaging them. The next decade of trials will determine whether this ancient-meets-modern strategy earns a permanent place in the cancer clinic.

Subject of Research: Gut microbiota modulation by traditional Chinese medicine to reduce chemotherapy-induced toxicity in gastric cancer

Article Title: Modulation of the gut microbiota by traditional Chinese medicine to attenuate chemotherapy-induced toxicity in gastric cancer: a review

Article References: Li, J., & Ji, F. (2026). Modulation of the gut microbiota by traditional Chinese medicine to attenuate chemotherapy-induced toxicity in gastric cancer: a review. Supportive Care in Cancer, 34(10), Article 1041. https://doi.org/10.1007/s00520-026-11290-w

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11290-w

Keywords: gastric cancer, chemotherapy toxicity, gut microbiota, traditional Chinese medicine, short-chain fatty acids, LPS, TLR4, NF-κB, NLRP3 inflammasome, dysbiosis, polysaccharides, integrative oncology