A Milk Fat Globule Membrane-enriched dairy co-product modulates gut Faecalibaculum rodentium metabolism in association with the prevention of cognitive impairment in aging male Wistar rats

Consumption of the milk fat globule membrane (MFGM) by infants is linked to enhanced neurodevelopment and sustained cognitive improvements later in life. Aging, by contrast, is often marked by neurodegeneration and cognitive decline-a growing concern in the U.S. as 6.9 million Americans live with Alzheimers disease (AD). As such, identifying interventions to prevent cognitive impairment are imperative. The whey protein phospholipid concentrate (WPPC), a dairy co-product, is enriched in MFGM glycoconjugates. Given the cognitive health benefits conferred by MFGM consumption in early life, we previously found that high-fat (HF) diet induced cognitive impairment in aging male Wistar rats was prevented by supplementating with a 1.6% or 10% WPPC in the diet, compared to control rats fed a low-fat (LF) diet. We hypothesized that WPPC exerts protective effects against cognitive impairment through the gut-brain axis by modulating gut microbial composition and metabolism. To test this, we analyzed 16S rRNA sequencing data from fecal samples of aged male Wistar rat (4 months old) fed a LF, HF, HF + 1.6% WPPC, or HF + 10% WPPC diet (n=9-10/group). Compared to LF, the HF diet reduced the abundance of the Erysipelotrichaceae family, particularly the species Faecalibaculum rodentium, which increased numerically with the 10% WPPC diet. Interestingly, Erysipelotrichaceae relative abundance correlated with hippocampal memory storage (spearman correlation=0.4, p=0.034). In vitro growth assays confirmed that F. rodentium grew robustly in isolation on WPPC glycoconjugates and on constituent WPPC components (p<0.05). RNA sequencing of F. rodentium grown on the WPPC MFGM glycoconjugates versus glucose (n=3/group) revealed significant upregulation of genes involved in in amino acid metabolism and fatty acid oxidation (FDR<0.05). Collectively this data suggests a potential role for F. rodentium in preventing cognitive impairment through the gut-brain axis by metabolizing the WPPC that may act on the host.