HomeNutritionDietary D-Lactate Intake Facilitates Inflammatory Resolution by Modulating M1 Macrophage Polarization

Dietary D-Lactate Intake Facilitates Inflammatory Resolution by Modulating M1 Macrophage Polarization

October 14, 2022

Mol Nutr Food Res. 2022 Oct 14:e2200196. doi: 10.1002/mnfr.202200196. Online ahead of print.

ABSTRACT

SCOPE: Given the D-lactate dehydrogenase (D-LDH) deficiency, L- but not D-lactate is assumed to be the physiological isomer in mammals. Paradoxically, many fermented foods (e.g., yogurt, sauerkraut, cheeses) often contain substantial amounts of D-lactate. In the present study, we hypothesized that dietary D-lactate may be a previously unrecognized nutrient aiding in inflammatory resolution.

METHODS AND RESULTS: The anti-inflammatory properties of D-lactate were evaluated in experimental colitis and endotoxemia. Oral administration of D-lactate favourably affected acute inflammation in two different mouse models. Analysis of lactate-the lactate receptor (the hydroxycarboxylic acid receptor 1 HCA1, formerly GPR81) signal axis in inflammation was performed in primary peritoneal macrophages and wild-type (WT) or GPR81 knockout (KO) mice. GPR81 KO mice are susceptible to endotoxic shock than WT mice, while D-lactate exerted its anti-inflammatory activities in a GPR81-dependent manner. Mechanistically, the activation of lactate-GPR81 axis might suppress LPS-TLR4 signaling by modulating M1 macrophage polarization. Although D-LDH deficiency in mammals impairs D-lactate clearance, it might prolong its plasma terminal half-life, and thus provide a pharmacokinetic advantage of D-lactate over L-lactate.

CONCLUSION: This study highlights housekeeping function of the lactate-GPR81 axis in inflammation control, and suggests that dietary intake of D-lactate may underlies Metchnikoff’s probiotic yogurt theory of life prolongation. This article is protected by copyright. All rights reserved.

PMID:36239154 | DOI:10.1002/mnfr.202200196

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About The Author

Patrick Blanchard MD

Meet Dr. Blanchard Dr. Blanchard’s medical practice is an embodiment of Integrative health which brings conventional and complementary approaches together in a coordinated way. Conveniently located in sunny Florida and over the internet with ValiseMD’s secure HIPPA compliant telXmed servers. Since 1994, patients with a wide range of challenging medical problems have achieved optimum health using the best of natural medicine, judiciously combined with high-tech innovations. Breakthroughs are often achieved even after patients have consulted mainstream specialists and holistic practitioners. Dr. Blanchard is founder and CEO of ValiseMD, Inc. He is board certified in Family Medicine since 1994 and awarded Fellow of the American Academy of Family Physicians in 2001. He received the ‘Teacher of the Year’ award from the University of Kansas School of Medicine at completion of his residency in Family Medicine. He completed a fellowship at Wake Forest University in the field of vascular neurosonology. He holds a medical patent in the field of Gastroenterology. He holds an unrestricted license to practice medicine and surgery in Florida. He started his medical career as a Emergency Medical Technician, then as a Paramedic and later a Medical Doctor.