Nobunao Ikewaki ¹ Koji Ichiyama ² Senthilkumar Rajappa ² Senthilkumar Preethy ³ Samuel JK Abraham ^4*

• ¹ Kyushu University of Medical Science, Nobeoka, Miyazaki, Japan
• ² GN Corporation, Kofu, Yamanashi, Japan
• ³ Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, Tamil Nadu, India
• ⁴ Faculty of Medicine, University of Yamanashi, Yamanashi, Japan

Author Samuel Abraham is a shareholder in GN Corporation, Japan which holds shares of Sophy Inc., Japan., the manufacturers of novel beta glucans using different strains of Aureobasidium pullulans; a board member in both the companies and also an inventor to several patents of relevance to these beta glucans. The article by Nakamura et al. on the ME-BYO index [1] presents a ground breaking approach rooted in the "Healthcare New Frontier" policy initiative of Kanagawa Prefecture in Japan. This innovative concept introduces the ME-BYO index as a tool to measure and visualize the dynamic changes in an individual's health status. ME-BYO, translating roughly to "no disease," represents the transitional phase between health and the onset of disease or disability. It emphasizes the importance of early intervention, as preventive strategies during this transition can effectively maintain or even reverse disease progression [1].The ME-BYO index is quantified using a 15-item measure that evaluates four key domains: metabolic function, locomotor function, cognitive function, and mental resilience. This comprehensive assessment offers a unique perspective on monitoring health in real time [1].However, we wish to highlight two critical aspects that can further refine the clinical application of the ME-BYO index: The NLR is an accessible and reliable marker of the immune response to both infectious and non-infectious stimuli. It provides a snapshot of the balance between innate immunity (represented by neutrophils) and adaptive cellular immunity (represented by lymphocytes).NLR is influenced by numerous factors, including age, race, medications, and chronic conditions such as coronary heart disease, stroke, diabetes, obesity, psychiatric disorders, solid organ cancers, anemia, and stress [2].The normal range of NLR in healthy adults typically falls between 1 and 2, while values above 3.0 or below 0.7 are often pathological. Importantly, an NLR in the "gray zone" of 2.3-3.0 may serve as an early warning signal for various pathological processes such as cancer, atherosclerosis, infection, inflammation, psychiatric disorders, and stress. NLR has been wellestablished as a prognostic marker, independently correlating with mortality in both the general population and specific disease groups (e.g., sepsis, pneumonia, COVID-19, cancer).Moreover, NLR has recently gained traction in clinical decision-making, particularly in managing patients with COVID-19 pneumonia [3]. BRMGs, alone or in combination, have demonstrated the ability to modulate the gut microbiome and its metabolites, impacting various disease states while promoting overall health [12,16,17]. Notably, they have shown efficacy in regulating the neutrophil-tolymphocyte ratio (NLR) in conditions such as metabolic disorders, cancer, and psoriasis [15,18,19]. In these studies, the modulation of NLR was particularly pronounced in individuals with elevated baseline NLR levels, underscoring the potential of beta-glucans to regulate immune function even in advanced disease states [20].The ability of these beta-glucans to influence NLR, especially in diseases like cancer and psoriasis [18][19][20], highlights their potential as a therapeutic tool for immune modulation. The observed reduction in elevated NLR levels in these conditions further reinforces their role in balancing immune responses, potentially aiding in the transition back to health as envisioned in the ME-BYO framework. Given the close relationship between NLR and immune function, beta-glucans could potentially modulate NLR and thereby influence the ME-BYO index during critical transitions in health. This approach aligns with the ME-BYO index's focus on early intervention, encouraging individuals to take proactive steps to maintain health and prevent disease progression.In conclusion, the ME-BYO index is a powerful tool for visualizing and managing health