Abstract Details

Title Mapping the Baseline Gut Microbiome Landscape in People at Risk for Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) S24 - Pregnancy, Pediatric MS, and Early MS (5:06 PM-5:18 PM)

Poster/Presentation
Number 009

Objective We examined the gut microbiome in asymptomatic individuals with first-degree family history of MS.

Background Gut microbiome may contribute to multiple sclerosis (MS) onset. The gut microbiome landscape in at-risk population such as family members needs detailed examination.

Design/Methods In a cross-sectional study of asymptomatic participants across the MS genetic susceptibility distribution, each participant completed the food frequency questionnaire (FFQ), and donated stool and blood samples. From FFQ, we calculated a diet quality score (DQS). From stool, we generated the gut metagenome profiles using shotgun sequencing. From serum, we measured the concentration of molecules produced by gut bacteria on a metabolome platform. We normalized the microbiome features (relative abundance of community and functions) by arcsine square root, filtered by feature frequency, clustered co-abundant groups (CAG) using a Bayesian community-detection method, and calculated the mean abundance of component gut microbiome features as a meta-feature of each CAG. We performed multivariate modeling with host factors and microbiome CAG meta-features, adjusting for age, sex, smoking, and body mass index.

Results The cohort included 80 self-reported Europeans (100%), 57 women (73%), with 37.7 years (SD 8.6) as mean age at sampling. Species CAG 1 is the most significantly associated CAG with host genetic risk score for MS susceptibility (beta=-0.0067+/-0.0026, p=0.013, FDR=0.079). Importantly, species CAG 1 includes a community of the gut bacteria reportedly associated with MS, some of which also play key roles in short-chain fatty acid (SCFA) production and metabolism (*): Akkermansia muciniphila, Faecalibacterium prausnitzii*, Lachnospiraceae*, Methanobrevibacter, Parabacteroides, Prevotella and Ruminococcus* members. When assessing the gut bacterial functions, CAG 111 is the most significantly associated CAG with DQS (beta=0.0028+/-0.0008, p=0.00068, FDR=0.082).

Conclusions

Human MS-susceptibility genetic factors are associated with a network of gut bacteria species. Our study begins to uncover the complexity of the gut microbiome in MS at-risk populations and highlights the importance of longitudinal examination.

Authors/Disclosures
Zongqi Xia, MD, PhD PRESENTER	The institution of Dr. Xia has received research support from National Institute of Health. The institution of Dr. Xia has received research support from Department of Defense. The institution of Dr. Xia has received research support from Genentech/Roche.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Yian Gu, PhD	The institution of Dr. Gu has received research support from NIH.
	No disclosure on file
	No disclosure on file
Philip De Jager, MD, PhD (Columbia University Irving Medical Center)	Dr. De Jager has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. De Jager has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Puretech. Dr. De Jager has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for roche. Dr. De Jager has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for biogen. The institution of Dr. De Jager has received research support from roche. The institution of Dr. De Jager has received research support from Biogen. The institution of Dr. De Jager has received research support from puretech.

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