Sreeya Cherlo

Introduction. Dysbiosis, an imbalance in the gut microbial community, and consequent lymphatic inflammation are associated with the development of a multitude of diseases.¹ Metabolic Endotoxemia is caused by the presence of endotoxins in the blood which are derived from gram-negative bacteria included in dysbiotic gut microbiota.¹ The translocation of microbiota from the gut to the tissues induces inflammation due to crosstalk between the gut microbiota and the host immune system.² Protective measures such as catechin-rich green tea extract (GTE) have proven to have potent anti-inflammatory functions by acting through prevention of dysbiosis induced gut barrier dysfunction and chronic inflammation in mice.³ However, no controlled studies in humans have evaluated the potential gut-level benefits of GTE to alleviate endotoxemia-associated inflammation.³ The protocol described herein will address this critical knowledge gap concerning the benefits of GTE catechins acting at the gut to attenuate endotoxin absorption.¹ Methods. Twenty persons with metabolic syndrome and twenty age/gender matched healthy persons were randomized to receive placebo or GTE, containing 890 mg of catechins for a daily course of four weeks followed by a month wash out period and a cross-over of diet.¹ Metabolic assessments including endotoxemia, catechin metabolites, and inflammatory responses were analyzed from blood samples taken on days 0, 14, and 28.¹ Linear Mixed effect models were used to determine baseline levels and multivariable regression analysis was used to define correlations between variables.¹ Results. GTE limits endotoxin translocation by increasing intestinal barrier function and downregulating the inflammatory response.² GTE limits toll-like receptor 4, nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB)-mediated inflammation, and endotoxin translocations, thus protecting against the inflammatory response.³ GTE dietary treatment effectively reduces hepatic inflammation by decreasing NFkB activation, which usually leads to liver injury.⁴ Catechins found in GTEs are responsible for anti-inflammatory effects seen in metabolic syndrome nonalcoholic steatohepatitis.⁵ Due to the Covid-19 pandemic, this clinical trial does not have any published results as of yet as research has been effectively paused.¹  Conclusion. This trial will provide the foundations for future disease progression control in persons with metabolic syndrome and will prove to be an effective therapeutic option to prevent metabolic disease complications.¹ Outcomes will not only provide foundation for mechanistic studies in vitro examining prebiotic and antimicrobial activities of GTE catechins relative to gut barrier function, but will also help to establish evidence-based dietary recommendations for a health-promoting, commercially translatable, catechin-rich food that can potentially reduce cardiometabolic morbidity.¹

1. Hodges JK, Zhu J, Yu Z, et al. Intestinal-level anti-inflammatory bioactivities of catechin-rich green tea: Rationale, design, and methods of a double-blind, randomized, placebo-controlled crossover trial in metabolic syndrome and healthy adults. Contemporary Clinical Trials Communications. 2020;17:100495. doi:10.1016/j.conctc.2019.100495.
2. Dey P, Sasaki GY, Wei P, et al. Green tea extract prevents obesity in male mice by alleviating gut dysbiosis in association with improved intestinal barrier function that limits endotoxin translocation and adipose inflammation. The Journal of Nutritional Biochemistry. 2019;67:78-89. doi:10.1016/j.jnutbio.2019.01.017.
3. Li J, Sasaki GY, Dey P, et al. Green tea extract protects against hepatic NFκB activation along the gut-liver axis in diet-induced obese mice with nonalcoholic steatohepatitis by reducing endotoxin and TLR4/MyD88 signaling. The Journal of Nutritional Biochemistry. 2018;53:58-65. doi:10.1016/j.jnutbio.2017.10.016.
4. Li J, Sapper TN, Mah E, et al. Green tea extract treatment reduces NFκB activation in mice with diet-induced nonalcoholic steatohepatitis by lowering TNFR1 and TLR4 expression and ligand availability. The Journal of Nutritional Biochemistry. 2017;41:34-41. doi:10.1016/j.jnutbio.2016.12.007.
5. Sasaki GY, Li J, Cichon MJ, Riedl KM, Kopec RE, Bruno RS. Green Tea Extract Treatment in Obese Mice with Nonalcoholic Steatohepatitis Restores the Hepatic Metabolome in Association with Limiting Endotoxemia‐TLR4‐NFκB‐Mediated Inflammation. Molecular Nutrition & Food Research. 2019;63(24):1900811. doi:10.1002/mnfr.201900811.