Bifidobacterium pseudocatenulatum LI09 could protect rats from D-galactosamine- (D-GalN-) induced liver injury. However, individual difference in the protective effects of LI09 on the liver injury remains poorly understood. The present study is aimed at determining the multiple intestinal bacteria associated with the better protective effect of LI09 against D-GalN-induced rat liver injury. Two rat cohorts, i.e., the nonsevere and severe cohorts, were divided based on their liver injury severity. Higher level of ALB and lower levels of ALT, AST, TBA, TB, IL-5, and MIP-3α were determined in the nonsevere cohort than the severe cohort. The alpha diversity indices (i.e., observed species, Shannon, and Pielou indices) did not yield significant differences between the intestinal microbiota of the nonsevere and severe cohorts. The intestinal microbiota composition was different between the two cohorts. Ten phylotypes assigned to Bacteroides, Clostridia_UCG-014, Clostridium Lachnospiraceae, Lachnospiraceae_NK4A136, and Parabacteroides were closely associated with the nonsevere cohort, among which, ASV8_Lachnospiraceae_NK4A136 was the most associated one. At the structure level, two groups of phylotypes with most correlations were determined in the intestinal microbiota networks of the two cohorts. Among them, ASV135_Lachnospiraceae_NK4A136 was the most powerful gatekeeper in the microbiota network of the nonsevere cohort. In conclusion, some intestinal bacteria, e.g., Lachnospiraceae_NK4A136, Parabacteroides, and Clostridium, were associated with the better protective effect of LI09 against D-GalN-induced rat liver injury. They were likely to enhance the effectiveness of LI09, and their clinical application deserves further investigation.

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Aims Liver damage has caused great illness in human beings. Bifidobacterium catenulatum LI10 has been determined with protective effect against D‐galactosamine‐induced liver damage. However, due to the sample limitation, the individual difference in its protective effect was not determined. The current study was designed to characterize the gut microbiota of LI10‐pretreated rats with lower levels of liver damage. Methods and Results A series of experiments and bioinformatic analyses were carried out. Two rat cohorts with different levels of liver damage were determined, that is, Non‐Severe and Severe cohorts. Six out of the seven measured liver function variables were lower in the Non‐Severe cohort, while four cytokine variables also yielded differences between the two cohorts. The Non‐Severe and Severe cohorts were determined with distinct gut microbiota, among which ASV14_Parabacteroides and ASV7_Bacteroides were most associated with Non‐Severe and Severe cohorts, respectively. Five phylotypes were determined as structural gatekeepers in the microbiota network of Non‐Severe cohort, ASV135_Lachnospiraceae_NK4A136 of which contributed most to the stability of the network. Conclusions The relevant findings suggest that some gut bacteria could benefit the protective effect of LI10 on lowering the severity of rat liver damage. Significance and Impact of the Study The bacteria benefiting the protective effects of potential probiotics could be further investigated for future clinical application.