McCance Center Seminar Series: Nanda Kumar Navalpur Shanmugam, PhD

Why It Matters

The work links gut inflammation directly to Alzheimer’s pathology, suggesting that microbiome‑targeted therapies could become a viable avenue to prevent or slow neurodegeneration.

Key Takeaways

• Gut inflammation can exacerbate Alzheimer pathology in mouse models.
• DSS-induced colitis causes microbiome dysbiosis and reduced beneficial bacteria.
• Systemic cytokines from gut breach blood-brain barrier, triggering neuroinflammation.
• Human studies link IBD and gut dysbiosis to higher dementia risk.
• Targeting gut-brain axis may offer novel therapeutic avenues for AD.

Summary

The McCance Center seminar featured Dr. Nanda Kumar Navalpur Shanmugam presenting recent work on how intestinal inflammation influences Alzheimer’s disease (AD). Using a dextran sodium sulfate (DSS)‑induced colitis model in 5xFAD mice, the study examined whether acute gut inflammation can accelerate amyloid deposition, blood‑brain barrier (BBB) disruption, and neuroinflammatory responses. Key insights include the demonstration that DSS treatment produces marked gut dysbiosis, with 16S rRNA sequencing revealing increased Bacteroidetes and reduced Bifidobacterium species. Colitic mice showed shortened colon length, epithelial erosion, and heightened immune cell infiltration, confirming successful induction of intestinal inflammation. Importantly, these peripheral changes correlated with elevated systemic cytokines, BBB permeability alterations, and increased microglial activation in the brain, suggesting a mechanistic link between gut‑derived immune signals and AD pathology. The presentation highlighted supporting evidence from human cohorts: elevated fecal calprotectin in AD patients correlates with poorer cognitive scores, and epidemiological data indicate a 5.5% higher dementia incidence among individuals with inflammatory bowel disease. In the mouse model, acute colitis amplified amyloid burden and neuroinflammatory markers, providing experimental validation of the gut‑brain axis hypothesis. These findings underscore the potential of targeting gut microbiota and intestinal inflammation as a therapeutic strategy for AD. By modulating microbial composition or mitigating gut‑derived immune activation, it may be possible to slow neurodegeneration and improve cognitive outcomes, prompting further translational research into microbiome‑based interventions.

Original Description

Nanda Kumar Navalpur Shanmugam, PhD, Research Associate at Massachusetts General Hospital and Instructor at Harvard Medical School, presents: Inflammation beyond the intestine: Colitis-induced immune changes in Alzheimer’s mouse model.

McCance Center for Brain Health Seminar Series: December 8, 2025.

https://www.massgeneral.org/neurology/mccance-center