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Session: Microbiome (Poster Theater Flash Session 8)

(PTFS08-06-23) Diet-Gut Microbiome Interaction at Single-Subject Resolution: A Series of N-of-1 Clinical Trials

Monday, July 24, 2023
10:25 AM – 10:29 AM ET
Location:  Fairfax
Disclosure(s):
Ju-Sheng Zheng, PHD: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: The interplay between diet and gut microbiome substantially influences host metabolism, but uncertainties remain regarding their relationships tailored for each subject given the huge inter-individual variability. This study aims to investigate diet-gut microbiome interaction at single-subject resolution and explore its subsequent effects on host blood glucose homeostasis.

Methods: We conducted a series of nutritional n-of-1 trials, in which 30 participants were assigned high-carbohydrate (HC) or low-carbohydrate (LC) diets in a randomized sequence across three cross-over periods lasting 72 days. We used shotgun metagenomic sequencing to profile the gut microbiome. Continuous glucose monitoring systems were used to measure interstitial glucose levels every 15 minutes during the HC or LC intervention period. Finally, we validated our findings in an independent cohort of 1219 participants with available metagenomics data.

Results: Our analysis included a total of 317 stool samples and more than 110,000 glucose measurements, which were collected repeatedly throughout the study. We demonstrated that the gut microbiome exhibited both intra-individual dynamics and inter-individual personalities during the dietary interventions. At the single-subject resolution, we observed person-specific response patterns to both interventional diets. For example, we found that clinically important species, such as Clostridium citroniae and Bifidobacterium longum, responded inconsistently to the identical HC diet across participants. Furthermore, we discovered a personal gut microbial signature represented by a carb-sensitivity score, which was closely correlated with glycemic phenotypes during the HC intervention stage. We validated the role of this score in the validation cohort and found that it reflects host glycemic sensitivity to the personal gut microbiota profile when sensing the dietary carbohydrate inputs.

Conclusions: This study highlights the feasibility of integrating nutritional n-of-1 trials with gut microbiome analysis to characterize microbial responses to dietary interventions at the single-subject resolution. Our findings represent a new paradigm for investigating the diet-microbiome interaction in the context of precision nutrition.

Funding Sources: National Natural Science Foundation of China