Multifaceted Role of Microbiota-Derived Indole-3-Acetic Acid in Human Diseases and Its Potential Clinical Application

Indole-3-acetic acid (IAA) is recognized as a common plant growth hormone. It is also detectable in mammals, as it can be produced by gut microbiota in the gut. Current research works have shown that IAA is a multifaceted compound with significant consequences for several physiological and pathological processes. Higher levels of IAA occur in chronic kidney disease because decreased renal clearance contributes to cardiovascular and liver dysfunction. In contrast, IAA demonstrates protective effects by modulating oxidative stress, inflammation, and lipid metabolism in nonalcoholic fatty liver disease. IAA also shows potential therapeutic benefits in lung disorders such as acute lung injury, pulmonary fibrosis, and chronic obstructive pulmonary disease. Furthermore, IAA shows potential as an adjunct in cancer therapy, where it synergizes with chemotherapy regimens by endorsing oxidative stress and autophagy. Beyond cancer-related applications and metabolic disorders, IAA's role in neuroinflammation, mainly in conditions such as sepsis-associated encephalopathy and depression, underscores its potential as a therapeutic agent targeting the gut-brain axis. Furthermore, IAA is a potent oral hypoglycemic agent with mitigating effects on metabolic disorders associated with obesity and diabetes. This review provides an overview of the diverse roles of IAA in disease pathophysiology, its therapeutic promise, and the need for further research to better understand its mechanistic pathways. Understanding these complex effects could pave the way for novel microbiota-based therapies to address a range of chronic diseases and improve patient outcomes.