By Andrea McBeth
The concept of oxidative stress represents an important system that I have wanted to dive into for a long time with you. This dynamic, also termed redox balance, epitomizes the ongoing balancing act our bodies perform in managing oxidative processes against antioxidative defenses. Essential for cellular function and overall vitality, this delicate equilibrium involves complex chemistry and electron transport. It is central to our understanding of aging and inflammaging as well as how our microbes contribute to these processes.
To simplify these concepts, let's employ a metaphor grounded in nature.
Envision your body as a vast landscape crisscrossed by rivers and streams, representing the redox processes crucial for maintaining life's balance and flow. In this landscape, ideal water levels symbolize redox homeostasis, necessary for nourishing the land without causing floods or droughts.
Oxidative stress is akin to a sudden surge in water flow – vital under normal circumstances but potentially disruptive when excessive, leading to overflow that can manifest as inflammation and diseases.
Central to this system are the mitochondria, much like the springs and sources feeding the rivers, pivotal for our metabolism and energy, but also creating a potential for, and sensitive to, overflow effects (oxidative damage).
Our body's defenses against potential oxidative stress floods or droughts involve a multi-tiered system of dams and levees (antioxidants and enzymes), supported by internal (our cellular processes) and external resources (dietary factors), collectively maintaining our internal waterways' delicate balance. In addition, it turns out that our human microbiota is also a key player in this interface.
Dysbiosis as Redox Imbalance: Navigating Microbiome Research's Complex Currents
As I have been navigating the microbiome research and thinking about Thaena®, it has become apparent that microbiome dysbiosis conceptually demands a broader perspective. Traditional views, categorizing bacterial species as 'good' or 'bad' based on gene identification, have failed to yield clear health or disease correlations, puzzling us regarding defining and treating microbiome dysbiosis. We here at Thaena® have long believed that the metabolic behavior of our microbiota is the functional readout we should be focusing on, or the postbiotics our microbes are making.
Sebastian Winter's recent review paper (1) introduces a compelling new perspective on understanding dysbiosis within this framework. It emphasizes the importance of examining the metabolism and redox chemistry of bacterial species and their environment. This approach delves into how these microbes respond and produce metabolites and the subsequent impact of these metabolites on the redox balance within the microbiome environment. It brings the concept of keeping the redox rivers within our body from overflowing in direct connection with the microbiota.
Winter's paper highlights that gut environment redox chemistry shifts might significantly influence the microbiota's composition and function. Lifestyle, environmental factors, stress, and immune modulation might impact the microbiome by altering its redox state.
This focus shift from categorizing bacteria by name to exploring their metabolic and redox dynamics in the context of dysbiosis, disease, and health. This could unveil new microbiome research avenues and important perspective. Understanding the microbiome's role in chronic diseases might lie in how our external factors influence gut metabolism and redox chemistry. It is also helping us understand how postbiotics may be having impacts on human health.
Impact of External Factors on Gut Redox Chemistry
Understanding the impact of diet and environmental factors on gut microbiota redox balance is crucial for exploring microbiota health. Components in our diet, such as pesticides and preservatives, can act as inducers of oxidative stress, affecting microbiota metabolism. (2)
This realization underlines the importance of food quality and sourcing, beyond just nutrient content. Small amounts of associated chemicals with our foods that act as antimicrobials or preservatives could be significantly influencing gut health by changing our microbes' metabolic environment. This emphasizes the value of clean, minimally processed fruits and vegetables in a new way in relation to dysbiosis. Our food isn’t just the food for our microbes, it is also creating the redox environment it is metabolizing in.
Polyphenols and Postbiotics: Nature’s Antioxidants
Polyphenols and postbiotics play a significant role in gut health within this new paradigm as well. Polyphenols in fruits and vegetables, known for their antioxidant properties, can beneficially modulate the gut microbiota and redox state. (3,4) A study on Rosa laevigata fruit polysaccharide extract demonstrates its potential to target redox balance and gut interface, influencing obesity and inflammatory responses in animals. (5)
Postbiotics, including those found in ThaenaBiotic®, may play a vital role in modulating the metabolism of the gut microbiome and in maintaining the redox balance within the gut through our human cells as well. Specifically, postbiotics from heat-killed Lactobacillus plantarum have demonstrated their ability to boost antioxidant activities in both animal and human studies. The heat-killed probiotics and postbiotics achieve this by enhancing the pathways of glutathione, a key antioxidant, and by upregulating essential hepatic antioxidant enzymes. (6,7)
In another connected set of studies, the administration of endogenous glutathione (GSH), shown to be upregulated in the studies above, was observed to offer protection against oxidative stress acutely. This was achieved by improving the function of the intestinal barrier and boosting antioxidant capacity in a pig model exposed to paraquat. (8) Application of quercetin - a plant derived polyphenol antioxidant was also shown to protect brain cells in tissue culture from oxidative stress induced toxicity by paraquat. (9) These findings are in line with Thaena®'s research, which showed that ThaenaBiotic® effectively protected C. elegans (worms) from paraquat exposure. Such insights are paving the way to a deeper understanding of the microbiome and its postbiotics, suggesting that they might play a central role in driving the production of endogenous antioxidants like glutathione in our bodies and protecting us against pesticides and oxidative stressors like paraquat.
The integration of ThaenaBiotic® and other health-promoting prebiotic and postbiotics into our diet can be seen as a strategic intervention in managing the redox balance within the gut. By offering a blend of beneficial microbial metabolites, ThaenaBiotic® stands as a pivotal component in maintaining a well-balanced 'river system' within our gut. It represents a promising approach to not only modulating the metabolism of gut bacteria but also enhancing the global redox chemistry of the gut and fostering healthy interactions with our human epithelial cells.
In conclusion, the health of our gut microbiome extends beyond the mere presence or absence of certain bacterial species. It is profoundly influenced by the metabolic and redox dynamics shaped by our diet and environmental exposures. Embracing dietary choices rich in antioxidants, like polyphenols, and incorporating healthful postbiotics like ThaenaBiotic®, can be key strategies in ensuring a harmonious balance within our gut's 'ecosystem', ultimately contributing to our overall well-being and resilience against diseases.
References
- Winter, S. E., & Bäumler, A. J. (2023). Gut dysbiosis: Ecological causes and causative effects on human disease. Proceedings of the National Academy of Sciences, 120(50), e2316579120.
- Sule, R. O., Condon, L., & Gomes, A. V. (2022). A Common Feature of Pesticides: Oxidative Stress-The Role of Oxidative Stress in Pesticide-Induced Toxicity. Oxidative Medicine and Cellular Longevity, 2022, 5563759.
- Michalak, M. (2022). Plant-Derived Antioxidants: Significance in Skin Health and the Ageing Process. International Journal of Molecular Sciences, 23(2). https://doi.org/10.3390/ijms23020585
- Zhang, X., Shao, J., Cui, Q., Ni, W., Yang, Y., & Yan, B. (2023). Bioactivities of Dietary Polyphenols and Their Effects on Intestinal Microbiota. Mini Reviews in Medicinal Chemistry, 23(3), 361–377.
- Zhang, X., Jin, C., Liu, H., Hu, Y., Zhou, Y., Wu, W., & Qin, S. (2023). Polysaccharide extract from Rosa laevigata fruit attenuates inflammatory obesity by targeting redox balance and gut interface in high-fat diet-fed rats. Food Science and Human Wellness, 12(2), 442–453.
- Izuddin, W. I., Humam, A. M., Loh, T. C., Foo, H. L., & Samsudin, A. A. (2020). Dietary Postbiotic Lactobacillus plantarum Improves Serum and Ruminal Antioxidant Activity and Upregulates Hepatic Antioxidant Enzymes and Ruminal Barrier Function in Post-Weaning Lambs. Antioxidants (Basel, Switzerland), 9(3). https://doi.org/10.3390/antiox9030250
- Lee, C.-C., Liao, Y.-C., Lee, M.-C., Cheng, Y.-C., Chiou, S.-Y., Lin, J.-S., Huang, C.-C., & Watanabe, K. (2022). Different Impacts of Heat-Killed and Viable Lactiplantibacillus plantarum TWK10 on Exercise Performance, Fatigue, Body Composition, and Gut Microbiota in Humans. Microorganisms, 10(11). https://doi.org/10.3390/microorganisms10112181
- Xiang, X., Wang, H., Zhou, W., Wang, C., Guan, P., Xu, G., Zhao, Q., He, L., Yin, Y., & Li, T. (2022). Glutathione Protects against Paraquat-Induced Oxidative Stress by Regulating Intestinal Barrier, Antioxidant Capacity, and CAR Signaling Pathway in Weaned Piglets. Nutrients, 15(1). https://doi.org/10.3390/nu15010198
- Saberi-Hasanabadi, P., Sedaghatnejad, R., & Mohammadi, H. (2024). Protective Effect of Quercetin against Paraquat-induced Brain Mitochondrial Disruption in Mice. Current Drug Safety, 19(1), 44–50.