Both fecal microbiota transplantation (FMT) and dietary fiber intervention were verified as effective ways to manipulate the gut microbiota, whereas little is known about the influence of the combined methods on gut microbiota. Here, we constructed “non-industrialized” and “industrialized” gut microbiota models to investigate the donor effect of FMT and diet effect in shaping the gut microbiota. Mice were transplanted fecal microbiota from domestic pig and received a diet with low-fiber (D) or high-fiber (DF), whereas the other two groups were transplanted fecal microbiota from wild pig and then received a diet with low-fiber (W) or high-fiber (WF), respectively. Gut microbiota of WF mice showed a lower Shannon and Simpson index (P < 0.05), whereas gut microbiota of W mice showed no significant difference than that of D and DF mice. Random forest models revealed the major differential bacteria genera between four groups, including Anaeroplasma or unclassified_o_Desulfovibrionales, which were influenced by FMT or diet intervention, respectively. Besides, we found a lower out-of-bag rate in the random forest model constructed for dietary fiber (0.086) than that for FMT (0.114). Linear discriminant analysis effective size demonstrated that FMT combined with dietary fiber altered specific gut microbiota, including Alistipes, Clostridium XIVa, Clostridium XI, and Akkermansia, in D, DF, W, and WF mice, respectively. Our results revealed that FMT from different donors coupled with dietary fiber intervention could lead to different patterns of gut microbiota composition, and dietary fiber might play a more critical role in shaping gut microbiota than FMT donor. Strategies based on dietary fiber can influence the effectiveness of FMT in the recipient.

Transforming the gut microbiota has turned into the most intriguing target for interventions in multiple gastrointestinal and non-gastrointestinal disorders. Fecal microbiota transplantation (FMT) is a therapeutic tool that administers feces collected from healthy donors into patients to help replenish the gut microbial balance. Considering the random donor selection, to maintain the optimal microbial ecosystem, post-FMT is critical for therapy outcomes but challenging. Aiming to study the interventions of different diets on recipients’ gut microbiota post-FMT that originated from donors with different diets, we performed FMT from domestic vs. wild pigs that are living on low-fiber vs. high-fiber diets into the pseudo-GF mouse, followed with fiber-free (FF) or fiber-rich (FR) diets post-FMT. Different patterns of gut microbiota and metabolites were observed when mice FMT from different donors were paired with different dietary fiber contents. Enrichment of bacteria, including Akkermansia and Parabacteroides, together with alteration of metabolites, including palmitic acid, stearic acid, and nicotinic acid, was noted to improve crypt length and mucus layer in the gut in mice FMT from wild pigs fed an FR diet. The results provide novel insight into the different responses of reconstructed gut microbiota by FMT to dietary fiber. Our study highlighted the importance of post-FMT precise dietary interventions.