Funabashi, M. | bioRxiv Science

bioRxiv2023

Preliminary Insights into the Effects of Spinal Manipulation Therapy of Different Force Magnitudes on Blood Biomarkers of Oxidative Stress and Pro-Resolution of Inflammation Mediators

IntroductionEvidence has reported that spinal manipulation therapy (SMT) leads to spine segmental hypoalgesia through neurophysiological and peripheral mechanisms related to regulating inflammatory biomarker function. However, these studies also showed substantial inter-individual variability in the biomarker responses. Such variability may be due to the incomplete understanding of the fundamental effects of force-based manipulations (e.g., patient-specific force-time characteristics) on a persons physiology in health and disease. This study investigated the short-term effects of distinct SMT force-time characteristics on blood oxidative stress and pro-resolution of inflammation biomarkers. MethodsNineteen healthy adults were clustered into three groups: control (preload only), target total peak force of 400N, and 800N. A validated force-sensing table technology (FSTT(R)) determined the SMT force-time characteristics. Blood samples were collected at pre-intervention, immediately after SMT, and 20 minutes post-intervention. Parameters of the oxidant system (total oxidant status, lipid peroxidation and lipid hydroperoxide), the antioxidant system (total antioxidant capacity and bilirubin), and lipid-derived resolvin D1 were evaluated in plasma and erythrocytes through enzyme-linked immunosorbent assay and colorimetric assays. ResultsOverall, 400N seemed to decrease blood oxidants, and 800N generally increased blood oxidants, decreased antioxidants and resolvin D1 mediator ConclusionOur findings indicate that different single SMT force-time characteristics presented contrasting effects on the systemic redox signalling biomarkers and pro-resolution of inflammation mediators in healthy participants, providing baseline information and direction for future studies in a clinical population.

physiology↗

bioRxiv2019

A metabolic pathway for bile acid dehydroxylation by the gut microbiome

The gut microbiota synthesize hundreds of molecules, many of which are known to impact host physiology. Among the most abundant metabolites are the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA), which accumulate at ~500 M and are known to block C. difficile growth1, promote hepatocellular carcinoma2, and modulate host metabolism via the GPCR TGR53. More broadly, DCA, LCA and their derivatives are a major component of the recirculating bile acid pool4; the size and composition of this pool are a target of therapies for primary biliary cholangitis and nonalcoholic steatohepatitis. Despite the clear impact of DCA and LCA on host physiology, incomplete knowledge of their biosynthetic genes and a lack of genetic tools in their native producer limit our ability to modulate secondary bile acid levels in the host. Here, we complete the pathway to DCA/LCA by assigning and characterizing enzymes for each of the steps in its reductive arm, revealing a strategy in which the A-B rings of the steroid core are transiently converted into an electron acceptor for two reductive steps carried out by Fe-S flavoenzymes. Using anaerobic in vitro reconstitution, we establish that a set of six enzymes is necessary and sufficient for the 8-step conversion of cholic acid to DCA. We then engineer the pathway into Clostridium sporogenes, conferring production of DCA and LCA on a non-producing commensal and demonstrating that a microbiome-derived pathway can be expressed and controlled heterologously. These data establish a complete pathway to two central components of the bile acid pool, and provide a road map for deorphaning and engineering pathways from the microbiome as a critical step toward controlling the metabolic output of the gut microbiota.

microbiology↗