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Association between dietary intake of live microbes and chronic obstructive pulmonary disease: a cross-sectional study of NHANES 2007–2012

Abstract

Background

Diet plays a crucial role in intervening in the development of chronic obstructive pulmonary disease (COPD), yet previous studies have not investigated the impact of dietary intake of live microbes on COPD. This study aims to assess the relationship between the two.

Methods

Participants from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012 were selected. The exposure variable was the estimated intake of live microbes in the diet, categorized into low, medium, and high groups. The outcome variable was COPD. A multivariable logistic regression model was used to assess the relationship between estimated dietary intake of live microbes and the risk of COPD.

Results

In the fully adjusted multiple logistic regression model, participants with moderate and high dietary intake of live microbes showed a negative association with the prevalence of COPD compared to those with low estimated intake, with reductions of 38% (OR, 0.62; 95% CI: 0.39–0.99, P < 0.05) and 44% (OR, 0.56; 95% CI: 0.34–0.92, P < 0.05) respectively. Additionally, subgroup analysis results remained stable with no observed interactions.

Conclusion

Our study suggests a negative association between higher dietary live microbe intake and the risk of COPD among adults in the United States.

Trial registration

ClinicalTrials.gov Identifier NCT00005154 First Posted date 26/05/2000(retrospectively registered).

Peer Review reports

Introduction

Chronic obstructive pulmonary disease (COPD) is a heterogeneous, irreversible inflammatory condition [1], affecting approximately 212 million individuals globally [2], imposing significant societal and economic burdens [3]. It is characterized by persistent and often progressive airflow obstruction due to airway and/or alveolar abnormalities [4]. The World Health Organization (WHO) predicts that by 2030, COPD will become the third leading cause of death globally [5]. Current treatment strategies for COPD primarily include long-term oxygen therapy, inhalers, smoking cessation, among others [6], but their impact on COPD progression is limited [7]. Therefore, identifying more effective prevention and management measures is considered a crucial pathway to alleviate the burden caused by COPD [8].

Increasing evidence suggests that diet plays a significant role in intervening in the development of COPD [9,10,11]. Furthermore, healthy dietary patterns as part of COPD management have been shown to reduce the risk of developing COPD, such as the Dietary Approaches to Stop Hypertension diet and the Mediterranean diet [12]. However, previous research seems to have overlooked the intake of live microbe in the diet. Studies have indicated that dysbiosis of the gut microbiota is an important component of COPD pathophysiology [13, 14]. A study supplementing probiotics in the diet of COPD mice showed that Lactobacillus reuteri and Bifidobacterium breve can prevent airway inflammation and lung damage [15]. However, besides consuming probiotic supplements, regular dietary intake, such as vegetables, meats, and fruits, is also rich in live microbes [16]. This provides a nutrition-based and easily implementable potential preventive strategy for COPD.

Currently, the relationship between dietary intake of live microbes and COPD remains unclear. Recently, Sanders ME et al. evaluated the quantity of live microbes in various foods and classified each food as having low (< 104 CFU/g), Medium (104–107 CFU/g), or high (> 107 CFU/g) levels of live microbes [17]. Therefore, we examined the association between estimated dietary intake of live microbes and COPD in U.S. adults based on data from the National Health and Nutrition Examination Survey (NHANES) and Sanders’ dietary live microbe classification system.

Materials and methods

Data source and participants

The NHANES survey is led by the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention (CDC) and has been prospectively registered on ClinicalTrials.gov (Clinical Trial Number: NCT00005154). It utilizes a complex multistage probability sampling design aimed at assessing the health and nutritional status of a nationally representative sample of adults and children in the United States. Currently, the NCHS collects and publishes data every two years, including demographic, dietary, examination, laboratory, and questionnaire data. The NHANES dataset is publicly available, and the study has been approved by the NCHS Research Ethics Review Board (ERB) (NCHS ERB Protocol Number: Continuation of Protocol #2005-06 and Protocol #2011-17), with all participants providing written informed consent.

In this cross-sectional study, we extracted a series of cross-sectional data from a nationally representative cohort as the basis for analysis, specifically including data from three NHANES cycles (2007–2008, 2009–2010, 2011–2012). Participants were excluded if they met the following criteria (Fig. 1): (1) individuals under the age of 20; (2) individuals with missing pulmonary function indicator data for the diagnosis of COPD; (3) individuals with missing dietary live microbe intake data; (4) individuals with missing covariate data such as age, gender, race, smoking status, hypertension, diabetes, etc. Ultimately, a total of 904 individuals met the inclusion criteria for this study.

Fig. 1
figure 1

Flow chart of this study

Definition and estimation of Dietary Live Microbe Intake

Dietary intake and energy information were estimated using 24-hour dietary recall data from NHANES, and the energy and nutrient content of each food and beverage were determined by the United States Department of Agriculture (USDA) Food and Nutrient Database for Dietary Studies, which can be linked to NHANES. The classification of estimated dietary live microbe intake levels in our study was determined based on assessments conducted by a panel of four experts (Maria L Marco, Mary E Sanders, Robert Hutkins, and Colin Hill). The experts estimated the quantity of live microbes contained in 9,388 food codes (Supplementary Material 1) across 48 subgroups (Supplementary Material 2-Table S1) in the NHANES database, relying on reported values in the literature, authoritative reviews, or inferred values based on known effects of food processing on microbial viability (such as pasteurization). Considering the expected variation in the quantity of live microbes among different types of food, each food was categorized based on the quantity of live microbes into three groups: low (Lo; <104 CFU/g), medium (Med; 104–107 CFU/g), or high (Hi; >107 CFU/g) [17]. Discrepancies in the classification process for each food were addressed through intra-team and inter-team consultations, as well as external advice. Here, Lo represents the quantity of live microbes in pasteurized foods (< 104 CFU/g), Med represents the quantity of live microbes in fresh fruits and vegetables consumed without peeling (104–107 CFU/g), and Hi represents the quantity of live microbes in unpasteurized fermented foods and probiotic supplements (> 107 CFU/g). Based on previous studies [18, 19], the estimated intake of dietary active microbes categorizes participants into the following groups: low dietary live microbe group (including participants rated as low); medium dietary live microbe group (including participants rated as medium, but excluding high); high dietary live microbe group (including participants rated as high).

Assessment of outcomes

The primary outcome variable for this study is COPD. Spirometry tests were administered to participants aged 6 to 79 years who met the inclusion and exclusion criteria during NHANES 2007–2012, with specific standards available on the NHANES website. We included participants aged 20 and above, collecting lung function-related indicators, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) measured after inhaling a bronchodilator. Additionally, NHANES provides FEV1 and FVC quality ratings based on American Thoracic Society (ATS) standards. We only included lung function measurement data with FEV1 and FVC quality ratings of A (exceeding ATS data collection standards) or B (meeting ATS data collection standards). COPD was defined as FEV1/FVC < 0.70 after inhaling a bronchodilator [4].

Covariates

The covariates considered in this study include age, gender, race, education level, marital status, body mass index (BMI), poverty income ratio (PIR), energy, smoking status, cardiovascular disease (CVD), hypertension, hyperlipidemia, and diabetes. Among them, race is divided into 4 categories: non-Hispanic white, non-Hispanic black, Mexican American, or other; education level is divided into 5 categories: Less Than 9th Grade, 9-11th Grade, High School Grad/GED, Some College or AA degree, College Graduate or above; marital status is divided into 3 categories: Married/cohabiting, Never married, Widowed/divorced/separated; BMI is divided into < 25 and ≥ 25 kg/m2; smoking status is divided into 3 categories: Never smoked, Former smoker, and Current smoker. Never smoked is defined as smoking fewer than 100 cigarettes in a lifetime, former smoker as smoking more than 100 cigarettes but not currently smoking, and current smoker as smoking more than 100 cigarettes and currently smoking. CVD is diagnosed based on self-reported diagnosis, with participants being defined as having CVD if a doctor has told them they have congestive heart failure (CHF)/coronary heart disease (CHD)/angina/heart attack/stroke. Hypertension is determined by self-reported high blood pressure, or average systolic blood pressure ≥ 140 mmHg, or average diastolic blood pressure ≥ 90 mmHg, or taking antihypertensive medication. The diagnosis of hyperlipidemia includes high-density lipoprotein (male ≤ 40 mg/dL, female ≤ 50 mg/dL), triglycerides ≥ 150 mg/dL, total cholesterol ≥ 200 mg/dL, low-density lipoprotein ≥ 130 mg/dL, or use of cholesterol-lowering medication. The diagnosis of diabetes is determined by physician diagnosis, taking glucose-lowering medication, random/2-hour oral glucose tolerance level ≥ 11.1 mmol/L, fasting blood sugar ≥ 7.0 mmol/L, or glycated hemoglobin (HbA1c) ≥ 6.5 mmol/L.

Statistical analysis

Our study first considered the complex sampling design and sample weights of NHANES. Participant characteristics were calculated based on whether they belonged to the COPD population. Categorical variables were presented as numbers and percentages (%), while continuous variables were presented as mean (standard deviation (SD)). Weighted t-tests were used for continuous variables, and weighted chi-square tests were used for categorical variables to compare significant differences in population characteristics.

We used a multivariable logistic regression model to assess the association between estimated dietary live microbe intake and the risk of COPD, with results presented as odds ratios (ORs) and 95% confidence intervals (CIs). We constructed regression models by stepwise adjustment of covariates: the crude model was unadjusted, model 1 adjusted for age, sex, and race; model 2 further adjusted for BMI, PIR, total energy intake, smoking status, marital status, and education level based on model 1; model 3 additionally adjusted for cardiovascular disease, hypertension, diabetes, and hyperlipidemia. Furthermore, linear trend tests were conducted by treating categorical variables as continuous parameters. Finally, stratified analyses and interaction tests were performed based on age (< 60 or ≥ 60 years), sex (male or female), smoking status (non-smoker or smoker), BMI (< 25 or ≥ 25 kg/m2), diabetes (yes or no), and hypertension (yes or no).

In addition, we conducted a related assessment on the majority of individuals with missing COPD data, using pre-bronchodilator lung function measures FEV1 and FVC (graded as A or B) as outcome variables. We employed a multivariate linear regression model to evaluate the association between estimated dietary intake of live microbes and lung function in these individuals, adjusting for covariates as described in the previous multivariate logistic regression model. The specific inclusion process is detailed in Supplementary Material 2-Figure S1. The statistical significance level was set at P < 0.05 (two-sided). All statistical analyses were conducted using R Studio (version 4.2.2).

Results

Baseline characteristics of the population

This cross-sectional study involved a total of 904 adult, with a weighted average age of 50 years (SD = 16). Among them, 412 were diagnosed with COPD (294 males [weighted proportion 68%], 118 females [weighted proportion 32%]). Compared to the non-COPD group, COPD patients were more likely to be Non-Hispanic White (278 individuals [weighted proportion 85%] vs. 256 individuals [weighted proportion 71%]), more obese (271 [weighted proportion 67%] vs. 304 [weighted proportion 63%]), had a higher proportion of smokers (312 [weighted proportion 73%] vs. 265 [weighted proportion 54%]), were mostly married/cohabiting (282 [weighted proportion 73%] vs. 312 [weighted proportion 64%]), and there were also statistically significant differences between the two groups in terms of CVD, hypertension, and hyperlipidemia (Table 1).

Table 1 Clinical characteristics of participants with and without COPD

Association between estimated dietary live microbe intake and COPD

The association between estimated dietary live microbe intake and COPD was evaluated through a multivariable logistic regression model. Four models were constructed, and the results are presented in Table 2. The findings indicated that the Crude Model did not show significant correlation. In Model 1, participants with high dietary active microbial intake had a negative association with the risk of COPD compared to those with low estimated intake (OR, 0.52; 95% CI: 0.33–0.84, P < 0.05). In Models 2, both moderate and high dietary active microbial intake were negatively associated with the risk of COPD compared to low estimated intake (Medium: OR, 0.61; 95% CI: 0.38–0.98, P < 0.05) (High: OR, 0.54; 95% CI: 0.33–0.89, P < 0.05). In Model 3, a similar negative association was found as in Model 2 (Medium: OR, 0.62; 95% CI: 0.39–0.99, P < 0.05) (High: OR, 0.56; 95% CI: 0.34–0.92, P < 0.05).Additionally, the prevalence of COPD significantly decreased (p for trend < 0.05).

Table 2 Association between levels of Dietary Live Microbe and COPD

Subgroup analyses

The subgroup analysis results on the association between estimated dietary intake of live microbes and COPD are depicted in the Fig. 2. Compared to individuals with estimated lower dietary active microbial intake, in the population under 60 years old (High: OR, 0.45; 95% CI: 0.24–0.82, P < 0.05), males (Medium: OR, 0.53; 95% CI: 0.34–0.84, P < 0.05; High: OR, 0.50; 95% CI: 0.25–0.99, P < 0.05), non-obese individuals (Medium: OR, 0.33; 95% CI: 0.13–0.81, P < 0.05), smokers (Medium: OR, 0.53; 95% CI: 0.30–0.92, P < 0.05), populations without diabetes (High: OR, 0.55; 95% CI: 0.33–0.93, P < 0.05), and populations without hypertension (High: OR, 0.43; 95% CI: 0.25–0.75, P < 0.01), moderate and/or high dietary active microbial intake in these subgroups is negatively correlated with the prevalence of COPD. Furthermore, in the mentioned subgroups, there was no significant interaction between the estimated dietary active microbial intake and COPD (all p for interaction > 0.05).

We conducted a pulmonary function assessment on the population with missing COPD data. The results indicate that, in terms of the overall population distribution, the weighted average age is 45 years (SD = 15), with a majority being Non-Hispanic White (weighted proportion 71%), obese (weighted proportion 69%), non-smokers (weighted proportion 54%), and married/cohabiting individuals (weighted proportion 63%). Additionally, a higher proportion of individuals in this population does not have CVD, diabetes, or hypertension. These demographic characteristics are generally consistent with the main study analysis population (complete COPD data population) as shown in Supplementary Material 2-Table S2.

The results of the multiple linear regression analysis model indicate that, in the fully adjusted model, there is a positive association between high estimated dietary intake of live microbes and FEV1 and FVC (β: 0.08; 95% CI: 0.04, 0.13, P < 0.01) (β: 0.09; 95% CI: 0.04, 0.14, P < 0.01), respectively. This suggests that higher intake of live microbes contributes to the improvement of lung function, while there is no significant association between FEV1/FVC (Table 3). Overall, these findings are consistent with the direction of previous results, suggesting a potential benefit in reducing the risk of COPD.

Table 3 Association between estimated dietary live microbe intake and lung function
Fig. 2
figure 2

Subgroup analyses. The results of subgroup analysis were adjusted for all covariates except the effect modifier

Discussion

In this cross-sectional study, we explored the association between dietary intake of live microbes and COPD as well as lung function, and to the best of our knowledge, this is the first study to investigate the relationship between dietary intake of live microbes and lung function. Our results suggest that compared to low-level intake, medium to high-level intake of dietary live microbes is negatively associated with the risk of COPD and positively correlated with lung function. This relationship persists even after adjusting for relevant covariates such as age, sex, race, PIR, BMI, marital status, smoking status, energy, hypertension, diabetes, CVD, and hyperlipidemia. Notably, the benefits of moderate to high-level dietary live microbe intake are more pronounced in individuals under 60 years old, males, non-obese individuals, smokers, those without hypertension, and without diabetes.

The bidirectional interaction between gut microbiota and lung microbiota is referred to as the “gut-lung axis” [15]. Previous studies have shown that patients with COPD exhibit overgrowth of taxa such as Actinomyces, Prevotella, and Streptococcus when compared to healthy individuals [20, 21]. Another clinical study involving fecal samples from 99 COPD patients and 73 healthy individuals demonstrated that COPD patients had a higher proportion of Firmicutes and a relatively lower proportion of Bacteroidetes compared to the healthy control group [22]. Additionally, a recent study in Australia found differences in fecal microbiota and metabolites between 28 COPD patients and 29 healthy controls, with Streptococcus identified as a key discriminatory factor between the COPD and healthy groups [23]. Additionally, an MR study revealed that an increase in the abundance of Genus Parasutterella is associated with decreased FEV1 and FVC [24], while another study indicated a negative correlation between the relative abundance of Proteobacteria and Neisseria and FEV1/FVC [25]. These findings suggest a profound impact of the gut microbiota on COPD and lung function, highlighting the existence of interactions between the gut and lungs.

Diet is considered a primary environmental factor influencing the composition of gut microbiota [26]. In our study, sources of moderately high dietary intake of live microbes mainly include fresh fruits, vegetables, and fermented foods, which are important sources of probiotics [27]. Probiotics, defined by the WHO as " live microbes that, when administered in adequate amounts, confer a health benefit on the host,” include strains such as Lactobacillus and Bifidobacterium, which possess strong antioxidant capabilities [28]. Additionally, Lactobacillus rhamnosus CRL1505 has been shown to increase levels of cytokines such as Interferon-alpha, and Interferon-beta in the lungs, thereby reducing respiratory inflammation [29]. Lactic acid bacteria, Lactobacillus reuteri, and Lactobacillus fermentum, apart from exhibiting antioxidant capabilities, also secrete short-chain fatty acids(SCFAs) to regulate the host’s pulmonary immune response [30, 31].

A prospective cohort study involving 35,339 individuals previously indicated a link between long-term high dietary fiber intake, primarily from fruits, vegetables, and grains, and a reduced risk of COPD [32]. Prospective cohort studies in the Chinese population also consistently show that regular consumption of fresh fruits can reduce the risk of developing COPD [33]. Several animal experiments further support the beneficial effects of a high-fiber diet and whey peptide-based enteral nutrition in alleviating pulmonary emphysema in mice [34, 35]. Regarding lung function, a cross-sectional study found that participants in the highest quintile of fiber intake had higher lung function measurements, including FEV1, FVC, and FEV1/FVC, compared to those in the lowest quintile [36]. Studies by Corrine Hanson et al. suggested that low fiber intake is associated with decreased lung function measurements [37]. A 10-year prospective study from the European Community Respiratory Health Survey indicated that higher intake of fruits and tomatoes can delay the decline in lung function [38]. Cook et al. even reported a positive correlation between FEV1 and the frequency of consuming fresh fruits and green leafy vegetables in 2,650 school-aged children [39]. One of the mechanisms by which high-fiber dietary intake maintains lung function and reduces the risk of COPD may be through alleviating systemic inflammation [40, 41]. Probiotics rich in dietary fiber can alter the composition of the gut microbiota, particularly changing the ratio of Firmicutes and Bacteroidetes, which can impact lung function [42], and increase the levels of SCFAs [43]. These SCFAs can directly affect peripheral immune cells, thereby reducing chronic airway inflammation in the lungs, improving intestinal barrier function, and reducing bacterial translocation [44].

The high intake of live microbes mainly involves the consumption of fermented foods and probiotic supplements. Previous studies have shown through multi-omics measurements of microbial composition and host parameters that the consumption of high fiber and high fermentation foods affects the microbiome and human biology in distinct ways, with a notable difference being their impact on gut microbial diversity [45, 46]. Recently, Wastyk et al. found that compared to a high-fiber diet, a diet rich in fermented foods (including fermented dairy, vegetables, and non-alcoholic beverages) led to an increase in alpha diversity of the gut microbiota, while no such change was observed with fiber intake [47].

Furthermore, fermentation can enhance the bioavailability of polyphenols in fermented foods. Dietary polyphenols, mainly known for their antioxidant properties like flavonoids, may help regulate lung function decline in elderly individuals exposed to cigarette smoke [48,49,50]. The role of probiotics seems to further reveal the connection between active microorganisms and COPD. Probiotics can prevent or improve COPD by regulating the gut microbiota ecosystem [15]. Some probiotic supplements, such as Lactobacillus rhamnosus, have emerged as a novel therapeutic approach for COPD patients. Administration of Lactobacillus rhamnosus increases anti-inflammatory cytokines in bronchial tissues, including transforming growth factor-beta and tissue inhibitor of metalloproteinases [51]. Probiotics like Bifidobacterium Breve and Lactobacillus rhamnosus also exhibit anti-inflammatory capabilities, inhibiting the release of Interleukin-6, Interleukin-1 beta, and Tumor Necrosis Factor alpha induced by cigarette smoke [52].In summary, increasing the intake of active microorganisms in daily diet can help improve gut barrier function, enhance gut microbiota diversity, alleviate inflammation and oxidative stress, thereby reducing the risk of COPD to some extent and regulating lung function.

Currently, the treatment of COPD primarily focuses on suppressing airway inflammation and alleviating symptoms. There is an urgent need for new measures to prevent and mitigate disease progression. The purpose of this study is to emphasize that consuming a diet rich in live microbes can reduce the risk of COPD in US adults. However, safety concerns regarding probiotics deserve attention, as there have been some adverse events reported in immunocompromised patients, including those in a weakened state or with malignant tumors [53]. Nevertheless, nutritional intervention as an adjunctive approach for preventing and managing COPD remains practically significant. It requires increased attention to individual health conditions, the promotion of personalized diets, and gradually enhancing public knowledge about the specific components of probiotics in dietary supplements to ensure their safety.

Certainly, our study has the following limitations. Firstly, based on Sanders’ dietary live microbe classification system, although it has been supported by previous research, it may be less accurate than directly measuring dietary microbes. Secondly, in this cross-sectional study, we observed this association but cannot determine causality. Thirdly, despite adjusting for confounding factors such as key demographic indicators, behavioral risk factors, and various chronic diseases, the results may still be influenced by unknown confounding factors, such as whether participants are taking relevant COPD medications and participants’ occupations. Finally, our study population consisted of US adults, so the generalizability of the results to other populations globally may be limited. Further research is needed to elucidate the underlying mechanisms.

Conclusion

Our study suggests a negative association between higher dietary live microbe intake and the risk of COPD among adults in the United States.

Data availability

All data for this study are publicly available. This data can be found here: The National Health and Nutrition Examination Survey dataset at https://www.cdc.gov/nchs/nhanes/index.html.

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Acknowledgements

The authors thank all the participants and researchers who contributed and collected data. Thanks to Zhang Jing (Second Department of Infectious Disease, Shanghai Fifth People’s Hospital, Fudan University) for his work on the NHANES database. His outstanding work, nhanesR package and webpage, makes it easier for us to explore NHANES database.

Funding

This work is supported by grants from the Jiangxi Clinical Medical Research Center of Lung Diseases (Gan ke fa she [2019] No. 44), Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program (No. CXTD22011).

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Contributions

XYF contributed to the conception and design of the study and data analysis. XYF and YZQ contributed to design of the study and wrote the first draft of the manuscript. LLJ contributed to the revision of the manuscript. All authors contributed to the article and approved the submitted version.

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Correspondence to Liangji Liu.

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The NHANES dataset is publicly available, and the study has been approved by the NCHS Research Ethics Review Board (ERB) (NCHS ERB Protocol Number: Continuation of Protocol #2005-06 and Protocol #2011-17), with all participants providing written informed consent.

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Xu, Y., Yan, Z. & Liu, L. Association between dietary intake of live microbes and chronic obstructive pulmonary disease: a cross-sectional study of NHANES 2007–2012. BMC Pulm Med 25, 33 (2025). https://doi.org/10.1186/s12890-024-03453-4

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