(P31-16-26) Curcumin Consistently Increase the Relative Abundance of Short-Chain Fatty Acid (SCFA)—Producing Bacteria Across Different Dietary and Disease Conditions in Mice

Objectives: Curcumin improves gut and systemic health through modulation of the gut microbiota, however, whether it consistently promotes specific microbial taxa across different pathophysiological and dietary conditions remains unclear. This analysis aimed to identify whether curcumin consistently increases specific gut microbiota in Alzheimer’s disease (3xTg-AD) and aged mice model under both normal chow diet (NCD) and high-fat, high-sugar diet (HFHSD) conditions.

Methods: Paired-end 16S rRNA V3–V4 sequencing reads of total 72 fecal samples from seven-month-old female 3xTg-AD mice (PRJNA1052364) and eighteen- to twenty-one-month-old C57BL/6 mice (PRJNA1165253) were analyzed using QIIME 2. Adapters, barcode and primers were removed using Cutadapt. Reads were merged, quality filtered, and denoised using Deblur to generate amplicon sequence variants (ASVs). Taxonomic classification was performed using the Ribosomal Database Project classifier and verified with EzBioCloud. ASVs present in fewer than 5% of samples were excluded, and differentially abundant taxa were identified using LEfSe (P < 0.05, LDA > 2.5).

Results: After primer and adapter trimming and quality control, 12,114,052 high-quality reads remained, averaging 168,250 ± 7,547 reads per sample. Denoising with Deblur generated 1,830 ASVs. Although the overall microbial compositions differed between two studies, several taxa were consistently enriched following curcumin supplementation. Clostridium leptum was significantly increased in NCD + curcumin-fed 3xTg-AD and aged mice, whereas Clostridium viride and Clostridium fessum were consistently enriched in HFHSD + curcumin-fed groups across both models. These taxa are known contributors to short-chain fatty acid (SCFA) production and intestinal homeostasis.

Conclusions: Curcumin supplementation consistently enriched SCFA-producing taxa, including C. leptum, C. viride, and C. fessum across both dietary regimens in aged and 3xTg-AD mice. They may represent a potential signature microbiome associated with curcumin intervention. Future studies, particularly fecal microbiota transplantation approaches, are needed to determine whether these microbiomes causally mediate the health benefits of curcumin.

Funding Sources: OTTOGI HAM TAIHO Foundation, Intramural Research Program of the National Institute on Aging