Butyrate Prevents the Pathogenic Anemia-Inflammation Circuit by Facilitating Macrophage Iron Export.

Most patients with inflammatory bowel disease (IBD) develop anemia, which is attributed to the dysregulation of iron metabolism. Reciprocally, impaired iron homeostasis also aggravates inflammation. How this iron-mediated, pathogenic anemia-inflammation crosstalk is regulated in the gut remains elusive. Herein, it is for the first time revealed that anemic IBD patients exhibit impaired production of short-chain fatty acids (SCFAs), particularly butyrate. Butyrate supplementation restores iron metabolism in multiple anemia models. Mechanistically, butyrate upregulates ferroportin (FPN) expression in macrophages by reducing the enrichment of histone deacetylase (HDAC) at the Slc40a1 promoter, thereby facilitating iron export. By preventing iron sequestration, butyrate not only mitigates colitis-induced anemia but also reduces TNF-α production in macrophages. Consistently, macrophage-conditional FPN knockout mice exhibit more severe anemia and inflammation. Finally, it is revealed that macrophage iron overload impairs the therapeutic effectiveness of anti-TNF-α antibodies in colitis, which can be reversed by butyrate supplementation. Hence, this study uncovers the pivotal role of butyrate in preventing the pathogenic circuit between anemia and inflammation.

Correlation between sagittal parameters and disability of patients with nonspecific chronic low back pain: a cross-sectional study of 435 subjects.

BACKGROUND CONTEXT: Sagittal parameters are significantly correlated with health-related quality of life (HRQoL) in adult spinal deformity patients. Their association with HRQoL in patients with nonspecific chronic low back pain (NSCLBP) is unclear. PURPOSE: To analyze the correlation between sagittal parameters and disability in NSCLBP patients. DESIGN: A cross-sectional study. PATIENT SAMPLE: Subjects included 435 patients with NSCLBP divided into low disability and high disability groups. OUTCOME MEASURES: Function was measured using the Oswestry Disability Index (ODI). Pain intensity was measured using the Numeric Rating Scale (NRS) and HRQoL was measured using 36-item Short Form Health Survey (SF-36). METHODS: Sagittal parameters, demographic data, ODI, SF-36 eight-dimensional scores and NRS scores of patients with NSCLBP were collected. Taking ODI=20 as the cut-off value, patients were divided into low disability group (ODI≤20) and high disability group (ODI>20), and ODI were converted to Ranked ODI (RODI) accordingly. Univariate analysis of the correlation among age, gender, body mass index (BMI), sagittal parameters, RODI, SF-36 eight-dimensional scores, NRS scores were then conducted. The variables related to RODI were analyzed by logistic regression to discover their independent influence on RODI. p<.05 was considered to indicate statistical significance. RESULTS: A total of 435 patients with NSCLBP were included. Univariate correlation analysis showed that the correlation coefficients between age, sacral slope-pelvic tilt (SS-PT), spinosacral angle (SSA) and RODI were (r=0.126, p<.01), (r=-0.115, p<.05), (r=-0.116, p<.05), respectively. The logistic regression analysis indicated that the regression coefficients of age and SSA were 0.030 (p=.001), -0.044 (p=.002), respectively, and the odds ratio and 95% confidence interval (CI) were 1.031 (1.012, 1.050), 0.957 (0.930, 0.985). CONCLUSIONS: Age and SSA are independent factors for disability of NSCLBP. SSA can comprehensively reflect the sagittal balance of the spine of patients with NSCLBP. Decreased SSA represents poor sagittal balance, which will increase the disability of NSCLBP.