Gouda MM. Gut-brain axis under attack: Links between diabetes, environmental toxicants, and neurodegeneration. World J Diabetes 2026; 17(7): 118334 [DOI: 10.4239/wjd.118334]
Corresponding Author of This Article
Mostafa M Gouda, PhD, Professor, College of Biosystems Engineering and Food Science, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou 310027, Zhejiang Province, China. mostafa-gouda@zju.edu.cn
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Endocrinology & Metabolism
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Gouda MM. Gut-brain axis under attack: Links between diabetes, environmental toxicants, and neurodegeneration. World J Diabetes 2026; 17(7): 118334 [DOI: 10.4239/wjd.118334]
World J Diabetes. Jul 15, 2026; 17(7): 118334 Published online Jul 15, 2026. doi: 10.4239/wjd.118334
Gut-brain axis under attack: Links between diabetes, environmental toxicants, and neurodegeneration
Mostafa M Gouda
Mostafa M Gouda, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310027, Zhejiang Province, China
Mostafa M Gouda, Department of Nutrition and Food Science, National Research Centre, Giza 12622, Egypt
Author contributions: Gouda MM was responsible for conceptualization, methodology, literature search, figure building, and writing the original draft of the manuscript.
AI contribution statement: The author takes full responsibility and accountability for all content of this manuscript, including any portions for which AI tools were used as assistive technologies. Grammarly was used solely for language polishing and typo correction. All Al-assisted outputs were carefully reviewed, validated, and approved by the author. No AI tools used to generate original scientific data, perform independent scientific analyses, or draw scientific conclusions.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Corresponding author: Mostafa M Gouda, PhD, Professor, College of Biosystems Engineering and Food Science, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou 310027, Zhejiang Province, China. mostafa-gouda@zju.edu.cn
Received: December 30, 2025 Revised: February 14, 2026 Accepted: May 14, 2026 Published online: July 15, 2026 Processing time: 192 Days and 0.8 Hours
Abstract
A recent study comprehensively summarized the environmental toxicants, microbiota, and diabetes linkage that increasingly interact to influence human susceptibility to neurodegeneration. Recent experiments show that simultaneous exposure to heavy metals and high blood sugar from diabetes causes more extensive neural dysfunction than either factor alone, partly through microbiota-driven inflammation and metabolic signaling. Multi-omics studies now indicate that gut dysbiosis, especially an increase in taxa such as Sutterella, is closely linked to changes in hippocampal proteins, oxidative stress, and disruption of the phosphoinositide 3-kinase/protein kinase B pathway, establishing a mechanistic link between peripheral metabolic damage and brain injury. These findings highlight the gut-brain axis as a key site where environmental pollutants, glucose imbalance, immune activation, and neurotransmitter issues interact to accelerate cognitive decline. The current opinion review explores how toxic metals and diabetes influence gut microbiota, promote neuroinflammation, affect neurotransmitter pathways, and alter neuronal proteomes. By understanding how environmental and metabolic stressors combine, novel insights could be achieved by integrating the gut microbiome with the brain axis, which is vital for reducing neurodegenerative risk in a world facing increasing pollution and metabolic challenges.
Core Tip: Emerging evidence shows that when diabetes coincides with environmental metal exposure, it significantly impacts the gut-brain axis. Hyperglycemia and toxicants together lead to gut dysbiosis, intestinal barrier breakdown, and increased neuroinflammation. This results in worse cognitive and hippocampal damage than each factor alone. Specific microbiota changes link metabolic toxicity to brain dysfunction, suggesting the need for prevention through reduced exposure and better glycemic control.
