Fungal Polysaccharide Helps Probiotics Survive the Gut and Fight Colitis in Mice

A crude polysaccharide extracted from the medicinal fungus Poria cocos has emerged as an unlikely ally for probiotic bacteria, according to a new study published in Frontiers in Microbiology. Researchers in China screened one hundred commercially available plant polysaccharides and found that Poria cocos polysaccharide, abbreviated PcP, was the only candidate that boosted the growth of all three bacterial strains in a widely used Chinese probiotic preparation by more than eighty percent. When the polysaccharide was co-administered with the probiotic in mice, the bacteria persisted far longer in the gut and the combination relieved chemically induced colitis more effectively than either component alone.

The probiotic preparation at the center of the study is Golden Bifid, a commercial three-strain formulation sold as Live Combined Bifidobacterium and Lactobacillus tablets by Inner Mongolia Shuangqi Pharmaceutical. It contains Bifidobacterium longum, Lactobacillus bulgaricus, and Streptococcus thermophilus, and is widely prescribed in China for gastrointestinal complaints ranging from infantile diarrhea to ulcerative colitis. Like all oral probiotics, however, it faces a fundamental obstacle: the stomach’s acidic gastric juice, the bile salts of the small intestine, and competition from the resident microbiota all conspire to kill incoming bacteria before they can establish themselves. This poor colonization efficiency, the authors argue, limits the clinical value of exogenous probiotic supplementation.

To find a fix, the team, led by Tingyu Li of Dalian Women and Children’s Medical Group together with Yan Wang and Chong Wang of Dalian Medical University, turned to plant polysaccharides, which can serve as fermentable carbon sources for beneficial bacteria. They cultured each of the three Golden Bifid strains with one hundred different crude polysaccharides at a concentration of one milligram per milliliter and monitored bacterial growth by optical density. Several polysaccharides promoted growth in individual strains, but only PcP cleared the eighty-percent improvement threshold for all three simultaneously. The researchers then confirmed the effect with purified preparations at two polysaccharide purities, fifty percent and eighty percent, and found that the higher-purity material performed better, suggesting the polysaccharide fraction itself drives the activity.

The in vitro characterization went well beyond simple growth curves. In artificial gastric juice at pH 3, artificial intestinal fluid at pH 8, and a one-percent bile salt solution, PcP supplementation significantly increased the survival rates of all three strains. Adhesion assays using Caco-2 human epithelial cells showed that co-incubation with PcP raised the adhesion rate of B. longum from 3.2 to 5.2 percent, L. bulgaricus from 29.4 to 48.0 percent, and S. thermophilus from 4.1 to 6.7 percent. Metabolite analysis by liquid chromatography-tandem mass spectrometry revealed that PcP also increased the bacteria’s output of short-chain fatty acids and lactic acid, with relative increases ranging from 66.3 to 74.7 percent for acetate, 30.0 to 56.3 percent for propionate, 28.0 to 49.0 percent for butyrate, and 11.1 to 35.0 percent for lactate.

The critical question was whether these laboratory effects would translate into a living gut. In a mouse persistence assay, animals received oral Golden Bifid alone or combined with PcP at 200 milligrams per kilogram of body weight for one week, with fecal samples collected over three weeks. Quantitative polymerase chain reaction targeting strain-specific genes showed that after one week of probiotic dosing alone, fecal abundance of the three strains rose to roughly 6.2-fold, 6.5-fold, and 6.1-fold baseline levels, then fell back to only 1.5 to 1.8-fold two weeks after dosing stopped. With PcP co-administration, the peak abundances soared to 13.2-fold, 32.4-fold, and 72.3-fold baseline, and levels of 3.5 to 13.9-fold baseline persisted two weeks after withdrawal. Throughout the observation period, the combination group maintained fecal abundances 3.5 to 17.6 times higher than the probiotic-alone group at the same time points.

The team then tested whether enhanced persistence translated into therapeutic benefit using a model of dextran sulfate sodium, or DSS, induced colitis in male C57BL/6 mice. Groups of six mice received PcP alone, Golden Bifid alone, or the combination, with treatment beginning one week before colitis induction. Both single agents reduced disease activity scores, colon shortening, plasma levels of FITC-dextran, a marker of intestinal barrier leakage, and colonic expression of the inflammatory cytokines IL-1β, TNF-α, IL-6, and interferon-gamma. But the combination outperformed both: mice receiving PcP plus Golden Bifid showed milder diarrhea and bleeding, less weight loss, fewer colonic ulcers, better preserved crypt architecture on histology, lower barrier permeability, and further reductions in inflammatory factor expression compared with either monotherapy.

The most mechanistically revealing experiment used antibiotic-treated mice whose native gut microbiota had been depleted with a cocktail of ampicillin, neomycin, metronidazole, and vancomycin. In these animals, PcP alone completely failed to alleviate DSS colitis, producing disease measures indistinguishable from untreated colitis controls. This indicates that PcP’s protective effect depends on the presence of a gut microbiota rather than a direct anti-inflammatory action on host tissue. Yet Golden Bifid retained its anti-colitic activity even in microbiota-depleted mice, and PcP still enhanced it. Fecal abundances of the three strains, which rose 77-fold, 124-fold, and 100-fold with Golden Bifid alone relative to colitis controls, climbed further to 174-fold, 202-fold, and 248-fold with the combination. Taken together, the authors conclude that PcP improves colitis outcomes mainly by boosting the persistence and activity of the supplemented probiotics rather than by acting directly on the host.

The proposed mechanism remains partly speculative. The three Golden Bifid strains lack the full enzymatic machinery to break down the high-molecular-weight beta-1,3-D-glucans enriched in PcP, so the authors suggest the growth-promoting activity may instead come from water-soluble heteropolysaccharide-derived oligosaccharide fragments that bacterial exo-acting glycoside hydrolases can process. They also raise the possibility of non-nutritional physical effects, with polysaccharide material acting as an outer-surface coating or adhesion matrix that shields bacteria from gastrointestinal stress and improves attachment to the intestinal epithelium. Importantly, the authors caution that these explanations derive from in vitro assays and do not constitute demonstrated causal mechanisms for the in vivo outcomes.

The study carries substantial limitations that the authors acknowledge candidly. The PcP used was a crude extract rather than a chemically defined molecule, so the observed effects could stem from polysaccharides or from co-extracted contaminants such as proteins and lipids, and the structural basis of the prebiotic activity is unknown. The fecal qPCR method used to quantify persistence cannot distinguish live, engrafted bacteria from residual DNA of dead, transit-excreted cells, so true mucosal colonization was not formally demonstrated; tissue-based fluorescence in situ hybridization would be needed. The antibiotic-depletion model itself may independently alter host intestinal physiology and DSS susceptibility, and the authors note their findings suggest microbiota involvement rather than proving microbiota dependence, with fecal microbiota transplantation experiments planned as a more definitive test. Only male mice were studied, leaving generalizability to females open, and the endogenous microbiota’s response to PcP was not fully characterized.

Even with those caveats, the work offers a concrete proof of concept for a strategy the authors describe as prebiotic plus probiotic: selecting a companion polysaccharide not for its own therapeutic action but for its ability to keep co-delivered bacteria alive and active.

Subject of Research: A prebiotic fungal polysaccharide that enhances probiotic persistence and anti-colitic efficacy in a mouse model of inflammatory bowel disease

Article Title: Poria cocos polysaccharide enhances the persistence and anti-colitic efficacy of three-strain probiotic preparation in DSS-induced colitis in mice

Article References: Li, T., Wang, Y., & Wang, C. (2026). Poria cocos polysaccharide enhances the persistence and anti-colitic efficacy of three-strain probiotic preparation in DSS-induced colitis in mice. Frontiers in Microbiology, 17, 1942804. https://doi.org/10.3389/fmicb.2026.1942804

Image Credits: AI Generated

DOI: 10.3389/fmicb.2026.1942804

Keywords: probiotics, prebiotics, Poria cocos polysaccharide, inflammatory bowel disease, colitis, gut microbiota, DSS-induced colitis, Bifidobacterium longum, Lactobacillus bulgaricus, Streptococcus thermophilus, intestinal persistence, mouse study