Gut Microbiota Was Reshaped in β-thalassemia Monkeys via the Blood-Gut Axis and Contributed to Gastrointestinal Symptoms

Patients with anemia caused by HBB gene mutations, such as β-thalassemia, are often present with gastrointestinal symptoms, the underlying mechanisms remain incompletely understood. In this study, we utilized deficient to create HBB-mutant cynomolgus monkeys and compared their gut microbiome characteristics to those of wild-type (WT) monkeys using metabolomic and metagenomic analyses. We found significant differences in metabolite profiles, particularly in amino acid and lipid metabolism pathways, with a notable discriminative metabolite (HMDB0254633). Metagenomic analysis demonstrated significant differences in the abundance of Lactobacillus and Bacteroides genera between the two groups, with the HBB mutants exhibiting a lower microbial diversity. Further functional analysis indicated that gene deficient significantly altered several key metabolic pathways, including amino acid and energy metabolism. These integrated findings suggest that HBB mutants potentially affect host metabolism and immune responses by modulating interactions between the gut microbiota and its metabolites. Additionally, we explored the impact of 3-Oxooctadecanoic Acid treatment on the intestinal flora of castor oil-induced diarrheal C57BL/6 mice. We assessed the rate and severity of loose stools, diarrhea index, and changes in body weight. In comparison, the high-dose (3_AOH) group alleviated diarrhea and improved the composition of the gut microbiota. This study, for the first time, demonstrates in non-human primates that β-thalassemia can influence gastrointestinal health by altering the homeostasis of the gut microbiota, and it was determined that 3-Oxooctadecanoic Acid can serve as a biomarker for both wild-type and HBB mutant cells. This offers valuable references for understanding the potential mechanisms underlying β-thalassemia symptoms, highlighting the impact of host genetic variations on gut microbiome regulation.