Suboptimal Health Status:risk Factors And Biological Mechanism

BackgroundChronic diseases have become the biggest threat to health in our country and become the main social and economic burden.Suboptimal health status(SHS)is the middle state between health and diseases,and it is an important window for the prevention and treatment of chronic diseases.It is considered that SHS is the outcome of the genes-environment interaction,and its occurrence and development is a process of stress response.Stress related risk factors can act as stressors and trigger the occurrence and development of SHS.Accordingly,based on the emerging link between the microbiota and health,and the gut microbiota playing an important role in stress response,we theorized a tempting new hypothesis for a strong connection between gut microbiota and SHS,the imbalances of gut microbial communities and metabolic disturbance may play an important role in SHS,which is likely to resulting from the complex interactions between the host microbiome and metabolism cross-talk.Therefore,basing on the complex physiological-psychological-social attributes of SHS,to explore the risk factors of SHS and to further clarify the biological mechanisms,will provide a new theory for the incidence of SHS,which may play a pivotal role for the predictive,preventive and personalized medicine.Methods1.To explore associations between SHS and TCM Constitution,and lifestyle,a cross-sectional survey was conducted within a clustered sample of 24,159 eligible individuals from 14 primary sampling units in 6 regions in Guangdong area,undertook the baseline survey,and a nested case-control study among healthy individuals was conducted,which was nested in a prospective cohort.2.To determine the role of gut microbiota imbalance and metabolic disturbance in SHS,cross-sectional design was firstly conducted and enrolled the health,SHS and disease individuals;on this basis,group-designed case-control studies were conducted,which marked SHS as case group,while the health or the disease individuals as control group.Results1.Study on risk factors for SHS:(1)The prevalence rates for the‘health',‘SHS'and‘disease'in Guangdong were 18.76%,46.03%,and 35.20%,respectively.SHS was with population differences,and different population had different prevalence rates.(2)The 1.5-year cumulative incidence was 42.66%for SHS.(3)Unbalance TCM constitution and unhealthy lifestyle were associated with the incidence of SHS.(4)SHS may be regression to health or progression to disease because of its bidirectional and translational nature;it is an important window for disease prevention.2.Study on biological mechanism for SHS:(1)SHS can be distinguished from the healthy individual in gut microbial diversity and community pattern,and serum metabolite cluster;while it was close to the disease state.(2)Compared with healthy individuals,a significant increase in the abundance of harmful bacteria in SHS,such as Ruminococcus gnavus,Ruminococcus,Ruminococcus torques,Streptococcus luteciae,Acinetobacter;while a significant reduction by Ruminococcaceae,Faecalibacterium,Faecalibacterium prausnitzii,Prevotellaceae,Prevotellaceae,Prevotella,Eubacterium biforme,Oscillospira,Odoribacter,Oxalobacter formigenes,etc.Compared with disease individuals,some beneficial bacteria were more abundance,like A.muciniphila;while some harmful bacteria decreased.19 metabolites enriched significantly in SHS individuals,including L-Isoleucine,L-Valine,L-Alanine,Citrulline,Aceticacid,L-Proline,L-Glutamine,L-Cystathionine,Dimethylsulfone,Glycerol,Creatine,L-Threonine,Urea,Uridine,Homovanillate,L-Tyrosine,L-Histidine,L-Phenylalanine,Benzoic acid;while 18 metabolites were lower expression,including L-Arginine,Glycylproline,L-Lysine,L-Glutamic acid,Carnosine,Sarcosine,L-Asparagine,L-Leucine,3-Hydroxybutyric acid,GTP,5'-Methylthioadenosine,ATP,Dehydroascorbic acid,D-Glucose,Traumatic acid,3-Methoxytyrosine,Indoxyl sulfate,Nicotinuric acid.(3)PICRUSt for microbial community function prediction showed that compared with healthy group,the microbiota of SHS was in the lower state of enzyme families,immune system,nervous system,and the immune disease activation function of SHS was significantly higher than that of health individuals.Moreover,significantly enriched for the proportion of genes in the microbiota of SHS related to some main metabolic pathways in Level 3 KOs,including phosphotransferase system,nucleotide metabolism,vitamin C metabolism,beta alanine metabolism,C5 branched chain acid metabolism,transcription associated proteins,metabolism of fructose and mannose and other related diseases.The results of functional enrichment and metabolic pathway analysis for serum metabolomics were consistent with the results of microbial community function prediction.(4)WGCNA analysis further showed that the significantly gut microbiota modules between SHS and health,were closely related to clinical features and serum metabolites.Conclusions1.Unbalance TCM constitution and unhealthy lifestyle are important risk factors for SHS,which can provide evidence and predictive,preventive,and personalized tool for SHS.2.The beneficial bacteria significantly decreased in SHS and the harmful bacteria increased,compared with healthy individuals;while compared with the disease,beneficial bacteria significantly increased in SHS and harmful bacteria decreased.This feature of the gut microbiota may be the biological basis for the bi-directional and translational nature of SHS.3.Biological processes change in SHS,including abnormal energy metabolism,decreased immune function,abnormal oxidative stress,metabolic disorders of bioactive substances(such as neurotransmitters,etc.)and increased metabolic waste.4.Gut microbiota is involved in the host metabolism of SHS,which is closely related to clinical features.