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Summary: Background: 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. Here we aim to investigate diet-gut microbiome interaction at single-subject resolution and explore its effects on blood glucose homeostasis. Methods: We conducted a series of nutritional n-of-1 trials (NCT04125602), in which 30 participants were assigned high-carbohydrate (HC) and low-carbohydrate (LC) diets in a randomized sequence across 3 pair of cross-over periods lasting 72 days. We used shotgun metagenomic sequencing and continuous glucose monitoring systems to profile the gut microbiome and blood glucose, respectively. An independent cohort of 1219 participants with available metagenomics data are included as a validation cohort. Findings: We demonstrated that the gut microbiome exhibited both intra-individually dynamic and inter-individually personalized signatures during the interventions. At the single-subject resolution, we observed person-specific response patterns of gut microbiota to interventional diets. 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, but not LC intervention. We validate the role of this score in the validation cohort and find that it reflects host glycemic sensitivity to the personal gut microbiota profile when sensing the dietary carbohydrate inputs. Interpretation: Our finding suggests that the HC diet modulates gut microbiota in a person-specific manner and facilitates the connection between gut microbiota and glycemic sensitivity. This study represents a new paradigm for investigating the diet–microbiome interaction in the context of precision nutrition. Funding: This work was supported by the National Key R&D Program of China, National Natural Science Foundation of China and Zhejiang Provincial Natural Science Foundation of China.

Background: The Guangzhou Nutrition and Health Study (GNHS) aims to assess the determinants of metabolic disease in nutritional aspects, as well as other environmental and genetic factors, and explore possible biomarkers and mechanisms with multi-omics integration. Methods: The population-based sample of adults in Guangzhou, China (baseline: 40–83 years old; n = 5,118) was followed up about every 3 years. All are tracked via on-site follow-up and health information systems. We assessed detailed information on lifestyle factors, physical activities, dietary assessments, psychological health, cognitive function, body measurements, and muscle function. Instrument tests included dual-energy X-ray absorptiometry scanning, carotid artery and liver ultrasonography evaluations, vascular endothelial function evaluation, upper-abdomen and brain magnetic resonance imaging, and 14-day real-time continuous glucose monitoring tests. We also measured multi-omics, including host genome-wide genotyping, serum metabolome and proteome, gut microbiome (16S rRNA sequencing, metagenome, and internal transcribed spacer 2 sequencing), and fecal metabolome and proteome. Results: The baseline surveys were conducted from 2008 to 2015. Now, we have completed 3 waves. The 3rd and 4th follow-ups have started but have yet to end. A total of 5,118 participants aged 40–83 took part in the study. The median age at baseline was approximately 59.0 years and the proportion of female participants was about 69.4%. Among all the participants, 3,628 (71%) completed at least one on-site follow-up, with a median duration of 9.48 years. Conclusion: The cohort will provide data that will be influential in establishing the role of nutrition in metabolic diseases with multi-omics.

Abstract Background Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive brain stimulation technique, has shown potentials for consciousness recovery of patients with disorders of consciousness (DoC), as, to a certain extent, it is effective in regulating the excitability of central nervous system. However, it is difficult to achieve satisfactory effect with “one size fits all” rTMS treatment due to different clinical conditions of patients. There is an urgent need to develop individualized strategy to improve the effectiveness of rTMS on patients with DoC. Methods Our protocol is a randomized double-blind sham-controlled crossover trial that includes 30 DoC patients. Each patient will received 20 sessions, in which 10 sessions will be rTMS-active stimulus, and the other 10 sessions will be sham stimulus, separated by no less than 10 days’ washout period. The rTMS-active will include 10 Hz rTMS over the individualized-targeted selection area for each patient according to the different insult regions of the brain. Coma Recovery Scale-Revised (CRS-R) will be used as primary outcome at baseline, after the first stage of stimulation, at the end of the washout period, and after the second stage of stimulation. Secondary outcomes will be measured at the same time, including efficiency, relative spectral power, and functional connectivity of high-density electroencephalograph (EEG). Adverse events will be recorded during the study. Discussion rTMS has obtained grade A evidence in treating patients with several central nervous system diseases, and there has been some evidence showing partial improvement on level of consciousness in DoC patients. However, the effectiveness of rTMS in DoC is only 30~36%, mostly due to the non-specific target selection. In this protocol, we present a double-blind crossover randomized sham-controlled trial based on the individualized-targeted selection strategy that aims to study the effectiveness of rTMS therapy for DoC, and the result may provide new insights to non-invasive brain stimulation. Trial registration ClinicalTrials.gov : NCT05187000. Registered on January 10, 2022.