A microbe–gut–cartilage chip linked a probiotic-exposed intestinal module to human cartilage organoids. Five enriched metabolites were subsequently tested on cartilage organoids made from pooled cells from three osteoarthritis donors.
Researchers at the Chinese University of Hong Kong and collaborating institutions built a chip with an intestinal epithelium, a separate cartilage-organoid compartment and controlled flow between them. The gut module supported an oxygen gradient, while the cartilage compartment received soluble products from the gut side. Cultures sampled from the cartilage compartment showed no detectable bacterial carryover. The linked design let the team compare cartilage exposed to probiotic-conditioned effluent with cartilage grown without that exposure.
A porous interface supported the intestinal epithelial layer, and the connected cartilage compartment contained an array of organoids. Flow modeling helped examine whether the organoids at different positions would experience comparable conditions. Barrier measurements and junction imaging provided checks on the gut side of the system.
The experiments examined cartilage maturation, resistance to a subsequent inflammatory challenge and responses after inflammation had already been induced. In organoids derived from bone-marrow stromal cells, probiotic-exposed gut effluent increased chondrogenic markers including COL2A1, SOX9 and ACAN, while reducing markers associated with cartilage degradation. The direction of Akt and ERK phosphorylation also depended on context: it rose during cartilage maturation but fell relative to inflamed controls after inflammatory challenge.
The profiling compared chips with and without the selected probiotics and identified enrichment in tryptophan-related and bile-acid-related metabolism. Docking suggested possible interactions with AhR and TGR5; thermal-shift measurements for selected compound–protein pairs added an experimental check on target engagement. Neither step established that a single receptor accounted for every protective effect of the mixed effluent.
Metabolite profiling identified 3-indolepropionic acid, indole-3-lactic acid, butyric acid, cholic acid and nicotinic acid among compounds enriched in the probiotic-exposed gut effluent. The researchers tested each candidate separately in cartilage organoids formed from chondrocytes donated by three people with osteoarthritis and pooled before culture. For this 72-hour metabolite experiment, the gut module was left empty, separating the effect of an added compound from continued microbial exposure.
Compared with untreated organoids, the reported treatments lowered secreted IL-6, MMP13 and CTX-2 and increased several cartilage-formation gene markers. Gene, secreted-protein and tissue-staining readouts showed different effects among the compounds; the paper singled out indole-3-lactic acid for effects on chondrogenic markers and 3-indolepropionic acid for several matrix-related measures. The secreted-protein and mRNA panels in Figure 10 used four chips per group, all drawing on the three-donor cell pool.
Three authors disclosed a pending Chinese University of Hong Kong patent related to the work.
The simplified system did not include liver metabolism, immune tissues or endocrine inputs that could modify a gut-derived compound before it reaches a joint in vivo. Its two selected strains and limited metabolite set were used to establish the platform, rather than to survey the full diversity of the microbiome. The patient-derived component also came from a small, female-only donor pool, leaving sex and donor variability unresolved in this experiment.
Two hiPSC-derived proximal tubule models show how transporter localization relates to directional drug transport and inhibitor responses. Transport activity and longer-term cell viability do not necessarily favor the same model.
A study connects aloperine binding and VPS34 lactylation to disrupted endosomal trafficking in lung cancer cells. Patient-derived organoids provided additional evidence of a stronger response to aloperine plus cisplatin than to either agent alone.
