| BackroundSecondhand smoke exposure has become an important public health problem,threatening the health of Chinese residents.Secondhand smoke exposure can increase the risk of various major chronic noncommunicable diseases(such as cardiovascular diseases and malignancies)and also increase the risk of premature death.Children and adolescents are in a critical period of physical and mental growth and development,and their organs and tissues are more sensitive to toxic and harmful substances than adults.The World Health Organization(2019)reported that exposure to secondhand smoke leads to 1.2 million deaths annually,and more than 65,000 children die each year from diseases related to secondhand smoke exposure.China is the largest tobacco producer and consumer in the world.Considerable work on tobacco control has been undertaken in China in recent years,including the protection of teenagers from secondhand smoke exposure,and prohibits all forms of tobacco advertising,promotion,and sponsorship.The current situation of secondhand smoke exposure among adolescents in China has been alleviated.However,the research on the current situation of secondhand smoke exposure among children and adolescents in Shandong Province is only based on some regions and cities,and the representativeness is relatively poor.It is not yet clear that the epidemiology of secondhand smoke exposure among children and adolescents in Shandong Province based on the representative data for the province.Therefore,it is necessary to expound on the epidemiology of secondhand smoke exposure among children and adolescents in Shandong Province to provide a basis for the government to formulate targeted tobacco control policies and measures.Many studies have shown that secondhand smoke exposure is related to short-term health damage among children and adolescents,including an increase in body mass index(BMI)or overweight and obesity.However,some studies have also shown that secondhand smoke exposure was associated with low weight,weight loss,stunting,and lower BMI among children and adolescents.Given that the association between secondhand smoke exposure and obesity among children and adolescents is not clear,and that previous studies have mostly been based on foreign populations,few studies have explored the association between secondhand smoke exposure and obesity among children and adolescents in China.In addition,previous studies have shown that lifestyle factors(such as diet and exercise)are closely related to childhood and adolescent obesity.However,it is not known whether secondhand smoke exposure and lifestyle factors jointly affect childhood and adolescent obesity.Therefore,it is necessary to explore the independent association between secondhand smoke exposure and obesity in different places among children and adolescents in China,as well as the interaction between secondhand smoke exposure and lifestyle factors on obesity,to provide new intervention directions for the prevention and control of childhood obesity.In addition to mechanisms such as genomics and epigenetics,microbiology has provided new ideas for exploring the biological mechanisms of human diseases in recent years.However,at present,there is still a lack of research on the association between secondhand smoke exposure,gut microbiota,and obesity in children and adolescents.Some studies have found that secondhand smoke exposure and obesity are both associated with changes in gut microbiota.Therefore,we hypothesized that secondhand smoke exposure might alter the gut microbiota,thereby affecting the occurrence of obesity.Identifying gut microbiota associated with both secondhand smoke exposure and childhood obesity,may provide scientific evidence for the disruption of the gut microbiota environment caused by secondhand smoke exposure and childhood obesity,and provide a new direction for the prevention and treatment of childhood and adolescent obesity.Objectives1.Based on the data from the Shandong Common Diseases and Health Influencing Factors Survey among Students in 2021,we aimed to describe the prevalence of secondhand smoke exposure among children and adolescents at home,schools,and in other public places in Shandong Province,and explore the spatial clustering characteristics of secondhand smoke exposure among children and adolescents at the district/county level in Shandong Province,and identify relevant influencing factors.2.Based on the data from the Shandong Common Diseases and Health Influencing Factors Survey among Students in 2021,we aimed to estimate the relationship between secondhand smoke exposure in different places and overweight and obesity,and investigated the interactions between secondhand smoke exposure and lifestyle indicators on obesity among children and adolescents.3.Based on the latest follow-up data of the "Huantai Childhood Cardiovascular Health Cohort" in 2021,we aimed to explore the relevant mechanism of gut microbiota between secondhand smoke exposure and obesity among children and adolescents,and identified the genus/species related to secondhand smoke exposure and obesity,and revealed which gut microbiota may be affected by secondhand smoke to induce obesity among children and adolescents.Methods1.Data collectionIn the first part of this paper,data on secondhand smoke exposure among children and adolescents in Shandong Province was extracted from the Shandong Common Diseases and Health Influencing Factors Survey among Students in 2021 in cooperation with the Shandong Center for Disease Control and Prevention.A questionnaire survey was used to collect information on students’ exposure to secondhand smoke at their homes,schools,and in other public places during the past 7 days.A total of 134,806 children and adolescents aged 8-18 years were included to describe the current situation of secondhand smoke exposure and identify the relevant influencing factors among children and adolescents in Shandong Province.The second part of this paper is also based on the data from the Shandong Common Diseases and Health Influencing Factors Survey among Students in 2021.The questionnaire survey was used to collect the lifestyle variables such as students’diet(whether to eat breakfast,the intake of sugary drinks,the intake of fried food,and the intake of fresh fruits and vegetables),daily video time,and exercise(the frequency of medium-high intensity exercise,the physical education class).Height and weight were measured by professional investigators.Based on the 134,806 children and adolescents aged 8-18 years in the first part of this paper,we further excluded 12,297 people with height,weight,and lifestyle variables loss and extreme abnormal value,and finally included 122,509 children and adolescents to explore the relationship between secondhand smoke exposure and obesity and the interaction between secondhand smoke exposure and lifestyle indicators on obesity among children and adolescents.In the third part of this paper,data used to explore the mechanism of gut microbiota related to children’s secondhand smoke exposure and obesity are from the latest follow-up data of the "Huantai Childhood Cardiovascular Health Cohort" in 2021.The project includes a questionnaire survey(children’s basic information,secondhand smoke exposure,diet,exercise,sleep time and drug use,etc.),physical measurement(height,weight,waist circumference,and body composition,etc.),and biological sample(stool)collection and detection.A total of 88 children aged 10-15 years were included for the association analysis between secondhand smoke exposure,gut microbiota,and childhood obesity.I participated in questionnaire data collection,on-site quality control,data management and statistical analysis in the first and second parts of the work,and in research design,stool collection,data management and statistical analysis in the third part of the work.2.Statistical analysis(1)Analysis of the current situation of secondhand smoke exposure in different places among children and adolescents in Shandong Province in 2021:First,describe the prevalence of secondhand smoke exposure among children and adolescents by gender,age group,suburb,and economic level in Shandong Province.Second,global autocorrelation analysis was used to determine whether there is a spatial correlation as a whole in the prevalence of secondhand smoke exposure among children and adolescents in Shandong Province.Local autocorrelation analysis was used to identify the spatial correlation in local areas in the prevalence of secondhand smoke exposure among children and adolescents.Third,multivariable logistic regression models were used to assess the potential influencing factors of secondhand smoke exposure.(2)Association of secondhand smoke exposure in different places with overweight and obesity among children and adolescents:First,a t-test was used to compare the BMI level between children and adolescents who were exposed to secondhand smoke and those who were not exposed,and chi-square test was used to compare the prevalence of overweight and obesity between children and adolescents who were exposed to secondhand smoke and those who were not exposed.Second,after adjusting the potential covariates(diet,exercise,video time,etc.),the logistic regression model was used to explore the relationship between secondhand smoke exposure in different places(at home,at school,and in other public places)and overweight and obesity among children and adolescents.Third,multiplicative and additive models were used to examine the impact of the interaction between secondhand smoke exposure and lifestyle variables(diet,exercise,video time,etc.)on overweight and obesity among children and adolescents.(3)Association of secondhand smoke exposure,obesity,and gut microbiota among children and adolescents:after 16SrRNA gene sequencing,sequence quality control and filtration of the subjects’ stool,relevant bioinformatics analysis(includingα diversity,β diversity analysis,correlation analysis,etc.)were conducted:First,compare the distribution and diversity of gut microbiota(phylum level,genus level,and species level)between the obesity group and the normal weight group.Rank regression was used to explore whether secondhand smoke exposure affected the diversity and distribution of gut microbiota in obese and normal-weight groups.Second,the heatmap analysis was used to explore the association of gut microbiota with indicators related to secondhand smoke exposure with obesity.After controlling the environmental factors that can affect the distribution of gut microbiota,the linear regression model was used to evaluate the gut microbiota related to secondhand smoke and obesity,and a logistic regression model was used to assess the association of secondhand smoke exposure related gut microbiota with obesity among children and adolescents.Third,receiver operating characteristic(ROC)analysis,integrated discrimination improvement index(IDI),and net classification improvement index(NRI)were used to assess the ability of secondhand smoke exposure with the screening of related gut microbiota to identify childhood obesity.Results1.In general,38.1%(95%Confidence Interval[CI]37.8-38.4)of children and adolescents in Shandong Province reported being exposed to secondhand smoke in any place at least one day during the past 7 days,18.2%(18.0-18.4)at home,6.7%(6.5-6.8)at school,and 23.9%(23.6-24.1)in other public places in 2021,respectively.The prevalence of secondhand smoke exposure among boys was slightly higher than that among girls.With the increase of age,the prevalence of secondhand smoke exposure also showed an upward trend(P<0.001).In 2021,the 5 cities where the prevalence of secondhand smoke exposure was highest were Zaozhuang City(50.0%),Linyi City(45.8%),Qingdao City(44.9%),Binzhou City(41.3%),and Jining City(41.1%),and the lowest was Rizhao City(18.2%).The results of local autocorrelation analysis show that Laoshan district and Chengyang district of Qingdao city,Mengyin county,Fei county,Lanshan district,Hedong district,and Lanling county of Linyi city,Shanting district,Shizhong district,Taierzhuang district,Tengzhou city,and Xuecheng city of Jining city are areas of high exposure to secondhand smoke.Multivariable logistic regression models suggested that secondhand smoke exposure was positively associated with boys(vs.girls:Odds Ratio[OR]=1.14,95%CI=1.12-1.17),higher age(13-15 years old vs.8-12 years old:OR=1.08,95%CI=1.05-1.11,16-18 years old vs.8-12 years old:OR=1.19,95%CI=1.15-1.22),urban status(urban vs.rural:OR=1.18,95%CI=1.15-1.21),and economic levels(middle vs.high:OR=1.20,95%CI=1.17-1.23,low vs.high:OR=1.16,95%CI=1.11-1.20).2.Adjusting for potential covariates,secondhand smoke exposure was positively associated with overweight among children and adolescents(in any place:OR=1.10,95%CI=1.06-1.13;at home:OR=1.10,95%CI=1.06-1.14;at school:OR=1.09,95%CI=1.02-1.15;in other public places:OR=1.06,95%CI=1.03-1.10).Secondhand smoke exposure was also positively associated with obesity among children and adolescents(in any place:OR=1.19,95%CI=1.15-1.23;at home:OR=1.21,95%CI=1.17-1.26;at school:OR=1.27,95%CI-1.20-1.35;in other public places:OR=1.12,95%CI-1.08-1.16).Further subgroup analysis and sensitivity analysis showed similar results.The interaction results showed that there were positive multiplicative interactions(interaction OR=1.18,95%CI=1.08-1.28)and positive additive interactions(Synergy index=2.02,95%CI-1.28-3.18)between secondhand smoke exposure and insufficient exercise on obesity among children and adolescents,while there were no multiplicative and additive interactions with other lifestyle variables(dietary factors,etc.)on overweight and obesity.3.Compared with children with normal weight,the richness and diversity of the gut microbiota in obese children are lower.Secondhand smoke exposure can significantly affect the diversity and distribution of gut microbiota between normal and obese children.After adjusting the potential covariates that can affect the distribution of gut microbiota,we found genus UBA1819(including species uncultured_organism_g_UBA1819 and OTU705),Eisenbergiella(including species uncultured_organism_g_Eisenbergiella and OTU972),Holdemania(including species uncultured bacterium_g_Holdemania)UCG-005(including species unclassified ug_UCG-005 and OTU214),unclassified_f_Eggerthellaceae,Norank_f_norank_o_Oscillospirales and species uncultured_Alistipes_sp._g_Alistipes(including OTU917)are negatively associated with secondhand smoke exposure and obesity-related indicators.However,the genus Tyzzerella(unclassified_g_Tyzzerella),Sarcina(uncultured bacterium_g_Sarcina),and species Clostridium_leptum_g_norank are positively associated with secondhand smoke exposure and obesity-related indicators.Further logistic regression analysis found that the genus related to secondhand smoke exposure were UBA1819,UCG-005,Holdemania,Eisenbergiella,unclassified_f_Eggerthellaceae and some of the species and OTU are negatively associated with obesity in children,while Tyzzerella and its species are positively associated with obesity in children.The ROC analysis results show that secondhand smoke exposure has a moderate ability to identify childhood obesity,with an area under the curve(AUC)of 0.672,while the above gut microbiota at the genus,species,and OTU levels can significantly improve the ability of secondhand smoke exposure to distinguish obese children from normal weight children(genus AUC:0.816,species AUC:0.813,OTU AUC:0.831).NRI and IDI analyses also suggest that the above gut microbiota can significantly improve the ability of secondhand smoke exposure to identify obese children.Conclusions1.There is a large difference in the prevalence of secondhand smoke exposure among children and adolescents across cities in Shandong Province.And there is an aggregation feature in the distribution at the district/county level,with relevant aggregation areas mainly distributed in the southern and eastern of Shandong Province.In the future,more attention should be paid to the tobacco control work in Zaozhuang,Qingdao,and Linyi.2.Children and adolescents exposed to secondhand smoke in different places(at home,at school,in other public places,and in any place)are associated with overweight and obesity.And there is an interaction between secondhand smoke exposure and insufficient exercise on childhood and adolescence obesity.Our findings suggest that providing a comprehensive smoke-free environment for children and adolescents needs the participation of society,schools,and families,as well as ensuring adequate exercise,which is of great significance in reducing the prevalence of childhood obesity.3.UBA1819,Eisenbergiella,Holdemania,UCG005,unclassified_f_Eggerthellaceae,Tyzzerella,Sarcina,uncultured_Alistipes_sp._g_Alistipes,Clostridium_leptum_g_Norank,and its related species or OTU were both associated with secondhand smoke exposure and childhood obesity.Secondhand smoke exposure combined with associated gut microbiota can better identify obese children.It is suggested that secondhand smoke exposure may lead to obesity in children by affecting the homeostasis of the gut microbiota. |
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