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Dietary live microorganisms and depression-driven mortality in hypertensive patients: NHANES 2005–2018

Journal of Health, Population and Nutrition volume 44, Article number: 117 (2025) Cite this article

Abstract

Objective

To investigate the relationship between dietary microorganism intake and mortality risk among hypertensive adults with depression in the United States.

Methods

This study utilizes data from the 2005–2018 National Health and Nutrition Examination Survey, focusing on individuals with hypertension. The Kaplan-Meier (K-M) curve is employed to preliminarily explore the relationship between dietary microorganism intake, depression, and mortality risk in hypertensive individuals. The Cox proportional hazards model is used for both individual and combined analyses of these relationships. Mediation analysis assesses the mediating effect of depression on the association between dietary microorganisms and mortality, while subgroup and sensitivity analysis evaluates the stability of the model.

Results

This cohort study included 11,602 hypertensive participants (5,904 men and 5,698 women), with 1,201 having depression. During follow-up period, 2,085 died from all causes, 692 due to cardiovascular events. Preliminary analysis using the K-M curve reveals that hypertensive individuals with higher dietary microorganism intake and those without depression have lower mortality risks. Cox proportional hazards model analysis shows that increased dietary microorganism intake is associated with reduced mortality risk in hypertensive individuals (HRALL−cause=0.654, 95%CI: 0.555–0.771; HRCVD−cause:0.675, 95%CI: 0.472,0.967). High intake of diets rich in dietary microorganisms may mitigate the ALL-cause mortality risk of depression in hypertensive populations(HRALL−cause=0.493, 95%CI: 0.256–0.947). Mediation analysis revealed that depression serves as a partial mediator in the process of dietary microorganisms improving the long - term prognosis of the hypertensive population. Results of subgroup analysis and sensitivity analysis showed that the beneficial effect of dietary microorganism intake on prognosis remained stable in most of the hypertensive population.

Conclusion

Patients with depression among those suffering from hypertension can reduce the risk of all-cause mortality caused by depression by increasing their intake of dietary microorganisms. This provides clinicians with a new non-pharmacological intervention approach and offers a direction for the optimization of clinical combined treatment regimens.

Introduction

Hypertension and depression are highly prevalent on a global scale. According to statistics from the World Health Organization, the number of individuals suffering from hypertension has surpassed one billion, and depression impacts the health of approximately three hundred million people worldwide [1–2]. Hypertension, as a primary risk factor for cardiovascular diseases, can give rise to severe consequences such as atherosclerosis, myocardial infarction, stroke, and heart failure. It stands as one of the leading causes of mortality and morbidity globally [3,4,5,6]. Concurrently, depression entraps patients in a protracted state of low mood, diminished interest, self-blame, and other distressing emotional states, severely disrupting their daily lives and social functions. It also substantially elevates the risk of suicide, imposing immeasurable psychological and emotional burdens on patients’ families [7,8,9]. These two diseases not only pose substantial challenges to patients’ health but also exert a considerable economic strain on public health systems.

Research has demonstrated that there exists a complex interplay between hypertension and depression, involving multiple pathways, including neuroinflammation, oxidative stress, endocrine dysregulation, and drug interactions [10–11]. On one hand, chronic hypertension can induce structural and functional alterations in cerebral blood vessels, disrupt cerebral hemodynamics, and inhibit the synthesis of crucial neurotransmitters such as serotonin and norepinephrine, thereby augmenting the risk of developing depression [12,13,14,15]. Moreover, certain antihypertensive medications, such as methyldopa, β-blockers, and calcium channel blockers, have been associated with depressive symptoms [16–17]. On the other hand, abnormal cortisol levels in patients with depression can increase the risk of metabolic syndrome, encompassing insulin resistance, hypertension, and abdominal obesity [18,19,20], which in turn further escalates the risk of cardiovascular diseases [21–22]. Commonly used antidepressant medications may also elevate the risk of hypertension through diverse mechanisms. For instance, tricyclic antidepressants can induce vasoconstriction and elevate blood pressure by blocking the reuptake of norepinephrine and exerting anticholinergic effects [23]. The selective serotonin reuptake inhibitor paroxetine has been reported to potentially lead to an increase in blood pressure [24]. Serotonin-norepinephrine reuptake inhibitors, such as venlafaxine and duloxetine, may also contribute to elevated blood pressure [25–26].

Notably, the gut microbiota also plays a pivotal role in cardiovascular and mental health [27–28]. Imbalance of the gut microbiota can disrupt neurotransmitter synthesis, immune regulation, and metabolic functions, thereby influencing cardiovascular and cerebral health and heightening the susceptibility to cardiovascular diseases and depression. Consequently, the status of the gut microbiota may represent a critical factor in the comorbidity mechanism of hypertension and depression [29–30]. Dietary microorganisms, particularly probiotics, have the potential to improve the composition of the gut microbiota, mitigate the risks of hypertension and depression, and enhance the health outcomes of affected individuals. This may be attributed to the ability of dietary microorganisms to modulate the gut microbiota, impact the gut-brain axis, and subsequently regulate the functions of the nervous and cardiovascular systems. Specifically, dietary microorganisms can regulate the production of various metabolites in the gut, such as short-chain fatty acids (e.g., γ-aminobutyric acid, tryptophan) [31], bile acids, and neurotransmitters (e.g., serotonin) [32], which can influence brain function and modulate mood and behavior. Additionally, gut microbiota dysbiosis can trigger an inflammatory response, leading to the release of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which contribute to the progression of cardiovascular diseases and depression [33,34,35]. Therefore, modulation of the gut microbiota is not only relevant to the health of the nervous and cardiovascular systems but also represents a promising avenue for future therapeutic strategies in the management of hypertension and depression. However, further large-scale, detailed clinical studies are imperative to elucidate these mechanisms comprehensively.

In light of the above, this study aims to utilize data from the National Health and Nutrition Examination Survey (NHANES) in the United States to systematically investigate the associations between dietary intake of live microorganisms, ALL-cause and CVD-cause mortality in individuals with depression and hypertension. We hypothesize that higher dietary intake of live microorganisms will be associated with a lower risk of mortality in hypertensive patients with depression. By exploring the potential impact of dietary live microorganisms on the long - term prognosis of these patients, this study endeavors to provide novel evidence for the relationship between dietary microorganisms, gut microbiota, and health. Additionally, it seeks to offer a fresh perspective on health strategies for hypertensive patients with depression, thereby contributing to a more comprehensive understanding of the measures required to control health risks associated with these and other related chronic diseases.

Materials and methodology

This study utilized the NHANES database, conducted by the National Center for Health Statistics (NCHS). NHANES is a comprehensive survey designed to collect representative information on the health and nutrition of the U.S. civilian population, encompassing demographics, socioeconomic status, dietary habits, and health-related issues. To ensure sample diversity, NHANES employs a stratified, multistage sampling method to select participants from across the nation. The study protocol was approved by the Research Ethics Review Board of the NCHS at the Centers for Disease Control and Prevention, and all participants provided written informed consent. Detailed information is available on the NHANES official website.

Inclusion and exclusion criteria for participants

The study collected data on 16,726 hypertensive participants from the 2005–2018 NHANES datasets available on the official website. Hypertension was identified based on self-reported responses to questions about prior diagnoses of hypertension by a physician, the use of antihypertensive medications, or an average of three blood pressure measurements (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg). Participants were further screened using the following exclusion criteria: missing survival data (n = 18, 0.11%), missing dietary data (n = 1721, 10.29%), missing PHQ − 9 questionnaire scores (n = 909, 5.44%), pregnant individuals (n = 51, 0.30%), missing data for other covariates include: marital status (n = 5, 0.03%), PIR (n = 1175, 7.02%), education (n = 11, 0.07%), CKD (n = 593, 3.55%), BMI (n = 137, 0.82%), smoking status (n = 6, 0.04%), drinking status (n = 497, 2.97%).

Ultimately, 11,602 participants were included in the final analysis. The detailed screening process is shown in Fig. 1.

Fig. 1
figure 1

Flow diagram illustrating the participant selection process

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Assessment of dietary live microbes and depression

This study evaluated participants’ dietary intake of live microorganisms using twice 24-hour dietary recall data in combination with the USDA Food and Nutrient Database. The content of live microorganisms in 9,388 foods across 48 subgroups within the NHANES database was determined by experts based on literature and food processing characteristics, with decisions made through consultation. Generally, aseptic or pasteurized foods were considered to have very low levels of live microorganisms, unpeeled raw fruits and vegetables contained moderate levels, and fermented foods were characterized by high levels. Foods were then classified into three categories: low (10⁴ CFU/g), moderate (10⁴–10⁷ CFU/g), and high (> 10⁷ CFU/g) levels of dietary microorganisms. Participants were assigned to one of three groups based on their dietary intake: the low dietary live microorganism group (consuming only foods with low levels), the moderate dietary live microorganism group (including foods with moderate levels but excluding high-level foods), and the high dietary live microorganism group (including foods with high levels). This classification method has been reported and applied in several studies [36–37].

In addition, depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9), which evaluates the frequency of depressive symptoms over the past two weeks. Scores for each item ranged from 0 to 3, with a total score ranging from 0 to 27. Based on the total score, depressive symptoms were categorized into five levels: “None or minimal” (0–4), “Mild” (5–9), “Moderate” (10–14), “Moderately severe” (15–19), and “Severe” (20–27). For the purpose of this analysis, participants with scores < 10 were classified as having no clinically significant depressive symptoms, while those with scores ≥ 10 were considered to have clinically significant depressive symptoms. Currently, the PHQ-9 uses a cutoff value of 10 for sever depression screening. This cutoff not only demonstrates high sensitivity and specificity in depression screening but also, through extensive practical applications, further proves that using it as a dividing line is of great significance and feasibility for accurately identifying patients with clinically significant depression [38,39,40].

Assessment of mortality

The National Center for Health Statistics (NCHS) linked NHANES data with the National Death Index (NDI) using identifiers such as Social Security numbers and birth dates to obtain survival status information for participants, with follow-up ending on December 31, 2019. If no match was found in the NDI, the participant was considered to have survived. Causes of death among survivors were classified according to the International Classification of Diseases, 10th Revision (ICD-10). For this study, cardiovascular disease mortality included conditions such as rheumatic heart disease, hypertensive heart disease, ischemic heart disease, cor pulmonale, cardiomyopathy, endocarditis, as well as cerebral hemorrhage, cerebral infarction, and others. The relevant ICD-10 codes for these conditions are I00-I09, I11, I13, I20-I51, and I60-I69 [41].

The covariates included in this study

Based on clinical experience and several previous studies, this research has taken into account multiple variables that may affect the relationship between dietary live bacteria and depression, as well as those that may impact cardiovascular and all - cause mortality risks [42–43]. These variables included various demographic characteristics of the study population, such as age, gender, race, education level, income-to-poverty ratio, BMI, and others. Additionally, lifestyle factors like smoking and alcohol consumption, as well as comorbid conditions such as diabetes and kidney disease, were taken into account. Daily calorie intake was also included as a variable. Smoking status was determined by the question “Have you ever smoked more than 100 cigarettes?” Current smoking status was assessed with the question “Do you currently smoke?” Individuals who reported smoking more than 100 cigarettes but no longer smoked were classified as former smokers. Alcohol consumption was categorized as follows: “Never drank” indicated fewer than 12 lifetime drinking occasions; “Former drinker” referred to individuals who had not drunk in the past year but had consumed alcohol more than 12 times in their lifetime; “Light drinker” was defined as consuming no more than two drinks per day for men and one drink per day for women; “Moderate drinker” included men consuming no more than three drinks per day and women no more than two, or those with binge drinking (defined as binge drinking 2 to 4 times per month); “Heavy drinker” referred to men consuming more than three drinks per day and women more than two, or those engaging in binge drinking five or more times per month. Diabetes and kidney disease were determined based on self-reported doctor diagnoses, laboratory tests, and medication use. Further details can be found on the NHANES website.

Statistical analyses

The statistical analyses in this study were conducted in strict accordance with the recommended design methodologies for the NHANES database, applying appropriate weights for each analysis. For continuous variables that followed a normal distribution, data were presented as mean ± standard deviation, while for non-normally distributed continuous variables, the median was used. For continuous variables, t-test or Kruskal-Wallis rank-sum test was selected for hypothesis testing. Categorical variables were presented as absolute numbers and percentages, and the chi-square test was used for hypothesis testing. Kaplan-Meier analysis was employed to preliminarily explore the relationship between dietary live microorganisms, depression, and all-cause as well as cardiovascular mortality in hypertensive populations, Subsequently, Schoenfeld residual tests were meticulously performed to evaluate the proportional hazards assumption underlying the Cox models. Consecutively, Cox proportional hazards regression models were rigorously implemented to explore the influence exerted by dietary live microorganisms and depression on both all - cause mortality and cardiovascular mortality. Further subgroup analyses were performed by dividing the population based on levels of dietary live microorganism intake and the presence or absence of depression, using Cox proportional hazards regression models, with results expressed as hazard ratios (HR) with 95% confidence intervals (CI). Three models were used for analysis: Model 1, unadjusted for confounding factors; Model 2, adjusted for demographic factors including age, sex, race, education level, poverty-to-income ratio (PIR), and marital status; and Model 3, further adjusted for BMI, alcohol consumption, smoking status, diabetes, kidney disease, and energy intake based on Model 2. Mediation analysis was performed using the “mediation” package in R to assess the mediating effect of depression on the relationship between dietary microorganism intake and mortality risk, adjusted for covariates such as age, gender, race, education level, income - poverty ratio, BMI, smoking status, drinking status, the presence of diabetes and kidney disease, and daily calorie intake. A significant mediating effect was indicated if the confidence interval did not include zero. Subgroup analyses were conducted to evaluate the stability and reliability of the findings in specific populations of interest. Missing covariate data was mainly handled via listwise deletion, preventing bias from unreliable imputation and maintaining data integrity. All analyses were conducted using R software (version 4.3.1), and statistical significance was defined as a two-sided P value < 0.05.

Results

Demographic and clinical attributes of participants

To better illustrate the clinical characteristics of hypertensive populations, this study categorized participants into low, medium, and high dietary microorganism intake groups. A total of 5,904 men and 5,698 women were included, among whom 1,201 had depression, 2,085 experienced all-cause mortality, and 692 died from cardiovascular diseases. Hypertensive individuals with high dietary microorganism intake constituted a smaller proportion of the total population, yet they tended to have lower BMI, higher educational attainment, higher income levels, and healthier lifestyle habits. They also exhibited a lower risk of metabolic conditions such as diabetes and chronic kidney disease, as well as reduced risks of cardiovascular and all-cause mortality. Moreover, it was observed that individuals with medium or high dietary microorganism intake had lower PHQ-9 scores and a reduced risk of severe depression compared to those with low dietary microorganism intake. Detailed results are presented in Table 1.

Table 1 Demographic and clinical characteristics of participants by dietary live microbes
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The Kaplan-Meier curves between dietary live microbes and depression with mortality in hypertensive patients

This study used Kaplan-Meier curves to preliminarily assess the association between dietary live microorganism intake, depression, and all-cause as well as cardiovascular mortality in hypertensive populations. Log-rank tests were performed to determine the significance of these associations. The results revealed a significant correlation between dietary live microorganism intake and both all-cause and cardiovascular mortality in hypertensive individuals. Those with a high intake of dietary live microorganisms had a lower risk of all-cause (log-rank PALL < 0.001) and cardiovascular (log-rank PCVD < 0.001) mortality compared to those with a low intake. Additionally, hypertensive individuals with depression exhibited higher risks of all-cause (log-rank PALL < 0.006) and cardiovascular (log-rank PCVD < 0.001) mortality than those without depression. Detailed results are shown in Fig. 2.

Fig. 2
figure 2

Kaplan-Meier analysis of dietary microbes intake and depression impact on mortality in hypertensive patients: (A) Dietary microorganism intake and ALL-Cause mortality risk in hypertensive patients (B) Dietary microorganism intake and CVD-Cause mortality risk in hypertensive patients (C) Depression and ALL-Cause mortality risk in hypertensive patients (D) Depression and CVD-Cause Mortality Risk in hypertensive patients

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Cox proportional hazards regression analysis of dietary live microbes and depression with mortality in hypertensive patients

To further analyze the impact of different depression statuses and dietary microorganism intake levels on the long - term prognosis of hypertensive populations, this study employed Cox proportional hazards models. Prior to interpreting the model results, Schoenfeld residual tests were conducted to assess the proportional hazards assumption. The results of these tests showed that the Schoenfeld residual test values for the associations between dietary live microbes and ALL-cause mortality, PHQ-9 and ALL-cause mortality, dietary live microbes and CVD-cause mortality, and PHQ-9 and CVD-cause mortality were 0.4279, 0.2413, 0.3837, and 0.4099, respectively. The test values were all greater than the critical value (P = 0.05), indicating that all models satisfied the proportional hazards assumption. Detailed results of the Schoenfeld residual tests can be found in Figures S1-4.

The subsequent results from the Cox proportional hazards models indicated that after adjusting for all covariates, each 1 - point increase in PHQ − 9 score was associated with a 3.1% increase in the risk of ALL-cause mortality among hypertensive individuals. Compared to individuals with a PHQ − 9 score below 10, those with a score above 10 had a 40.8% higher risk of all - cause mortality. Regarding dietary microorganism intake, hypertensive individuals with moderate intake exhibited a 24.1% reduction in ALL-cause mortality risk, while those with high intake showed a 34.6% reduction compared to those with low intake. In terms of CVD-cause mortality, each 1 - point increase in PHQ − 9 score was associated with a 3.3% increase in risk, and individuals with a PHQ − 9 score above 10 had a 45.8% higher risk compared to those scoring below 10. Hypertensive individuals with moderate and high dietary microorganism intake experienced reductions in CVD-cause mortality risk of 25.2% and 32.5%, respectively, compared to those with low intake. Detailed results are presented in Table 2 and Table 3.

Table 2 Association between dietary live microbes and depression with ALL-cause mortality in hypertensive patients across Cox proportional hazards models
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Table 3 Association between dietary live microbes and depression with CVD-cause mortality in hypertensive patients across Cox proportional hazards models
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Joint association of dietary live microbes and depression with mortality in hypertensive patients

To investigate the impact of varying dietary microorganism intake levels on hypertensive individuals with depressive symptoms, we performed stratified and combined analyses. The results indicated that, among hypertensive populations, compared to individuals with a PHQ-9 score greater than 10 and low dietary microorganism intake, those with a PHQ-9 score greater than 10 but high dietary microorganism intake exhibited a 50.7% reduction in all-cause mortality risk. Remarkably, this group’s mortality risk was even lower than that of individuals with a PHQ-9 score below 10 but low or moderate dietary microorganism intake, whose risks decreased by 31.5% and 47.8%, respectively, compared to the reference group. A similar trend was observed for cardiovascular mortality risk. Although Model 3 did not show a statistically significant effect of high dietary microorganism intake on hypertensive individuals with a PHQ-9 score above 10, Model 2 revealed a significant association (P = 0.039). Additionally, the overall trend demonstrated a clear association between dietary microorganism intake and reduced mortality risk in hypertensive individuals with depression (P for Trend = 0.001). Detailed results are presented in Tables 4 and 5, as well as Fig. 3.

Table 4 Association between the combined effects of dietary live microbes and depression on ALL-Cause mortality in hypertensive patients across Cox proportional hazards models
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Table 5 Association between the combined effects of dietary live microbes and depression on CVD-Cause mortality in hypertensive patients across Cox proportional hazards models
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Fig. 3
figure 3

Joint association of dietary live microbes and depression with mortality in hypertensive patients: (A) Dietary microbial intake and depressive status on ALL-cause mortality in hypertensive populations (B) Dietary microbial intake and depressive status on CVD-cause mortality in hypertensive populations

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Mediation analysis

This study evaluated the mediating role of PHQ-9 scores in the relationship between dietary microorganism intake and mortality among hypertensive populations, aiming to clarify whether depression mediates this association. After adjusting for all considered covariates, including smoking, drinking, age, gender, race, and other factors comprehensively accounted for in the study design, in the mediation analysis, the results demonstrated a mediating effect of depression on the relationship between dietary live microorganisms and mortality in terms of ALL-cause and CVD-cause mortality. For ALL-cause deaths, the estimated mediating effect was − 0.0011 (95% CI: -0.0018 to -0.0005, P < 0.0001), and the proportion mediated was 2.34%; for CVD-cause mortality, the estimated mediating effect was − 0.0006 (95% CI: -0.0009 to -0.0002, P < 0.0001), and the proportion mediated was 2.51%. Despite their relatively minor magnitudes, the findings offer novel perspectives on the intricate associations among dietary live microorganisms, depression, and mortality. Specifically, depression was determined to exert a partial mediating role in the improvement of the hypertensive population’s prognosis by dietary microorganisms. This implies that dietary live microorganisms influence mortality not solely through a direct pathway but also indirectly by alleviating depression. Details are presented in Fig. 4 and Table S1.

Fig. 4
figure 4

The Mediating effect of depression: (A) Depression as a mediator in the relationship between dietary microbial intake and ALL-cause mortality risk (B) Depression as a mediator in the relationship between dietary microbial intake and CVD-cause mortality risk

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Subgroup analysis

To assess the stability of the effects of dietary microorganism intake and depression on prognosis across different hypertensive subpopulations, subgroup analyses were conducted. The results showed no significant interactions with outcomes across different genders, BMI categories, ages, diabetes statuses, or kidney disease statuses, indicating that the findings of this study remain consistent across various subgroups. Detailed results of the subgroup analysis are provided in Supplementary Table 2.

Sensitivity analysis

In an effort to comprehensively appraise the robustness of the relationships between dietary microorganism intake, depression, and the risks of ALL-cause and CVD-cause mortality among hypertensive patients, we conducted a sensitivity analysis. This involved integrating two covariate states: the consumption of any antihypertensive medication and the utilization of any antidepressant medication. The ensuing results demonstrated that dietary microorganisms continued to exert a significant mitigating effect on the mortality risk associated with depression. Evidently, augmenting the intake of dietary microorganisms emerges as a viable and efficacious strategy for ameliorating the prognosis of hypertensive patients with comorbid depression. Details are presented in Table 6 and Table 7.

Table 6 Sensitivity analysis of the impact of dietary live microbes and depression on ALL-cause mortality in hypertensive patients
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Table 7 Sensitivity analysis of the impact of dietary live microbes and depression on CVD-cause mortality in hypertensive patients
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Discussion

This cohort study included data from 11,602 hypertensive participants collected by NHANES between 2005 and 2018, comprising 5,904 men and 5,698 women, of whom 1,201 had depression. During the follow-up period, there were 2,085 all-cause deaths and 692 cardiovascular deaths. Preliminary Kaplan-Meier analyses of depression and dietary microorganism intake revealed that both were associated with mortality risk in hypertensive individuals. Specifically, those with depression exhibited higher mortality risks, while greater dietary microorganism intake was linked to lower mortality risks. To further investigate the long-term prognostic impact of these factors on hypertensive populations, Cox proportional hazards models were employed. The results reaffirmed the significant associations of both depression and dietary microorganism intake with prognosis. Moreover, combined analyses showed that higher dietary microorganism intake may mitigate the increased mortality risk associated with depression in hypertensive individuals.Mediation analyses further demonstrated that dietary microorganism intake could reduce mortality risk by alleviating depressive symptoms. Subsequent subgroup analyses found no significant interactions across different demographic and clinical subgroups, underscoring the robustness of the findings. In conclusion, this study presents a compelling observation: increasing dietary microorganism intake may help reduce the mortality risk associated with depression in hypertensive patients. This finding provides a novel perspective and potential intervention strategy for the integrated management of hypertension and depression comorbidities, while also offering robust empirical support for exploring the role of dietary microorganisms in chronic disease management.

Recent studies have shown that gut microbiota dysbiosis is not only closely linked to the development of hypertension but may also exacerbate depressive symptoms through various mechanisms. In the case of hypertension, the relationship between gut microbiota alterations and elevated blood pressure has received increasing attention. A growing body of research has identified significantly reduced gut microbiota diversity in hypertensive patients, with a decreased proportion of beneficial bacteria such as Lactobacillus and Bifidobacterium, alongside an increased abundance of potential pro-inflammatory bacteria, including Prevotella from Bacteroidetes, Klebsiella from Proteobacteria, and Ruminococcus from Firmicutes [44,45,46]. This dysbiosis leads to elevated levels of bacterial by-products such as lipopolysaccharides and peptidoglycans [47–48], which trigger systemic inflammatory responses, impair endothelial cell function, and promote the progression of depression, further aggravating both elevated blood pressure and depressive symptoms. Dietary interventions and microbiota-targeted treatments, such as probiotic supplementation, have been found to help address these issues. Research indicates that supplementation with specific probiotics [49–50], including strains like Lactobacillus acidophilus and Bifidobacterium breve, as well as other beneficial microorganisms [51–52], such as Bacillus subtilis natto and Saccharomyces boulardii, can restore gut microbiota diversity and indirectly enhance the production of SCFAs like acetate, butyrate, and propionate [53–54]. These SCFAs exert multiple beneficial effects, including promoting vasodilation, regulating inflammatory responses, and modulating calcium ion channels and signaling pathways [55,56,57]. These mechanisms not only mitigate vascular damage and lower blood pressure but also regulate neurotransmitter metabolism and function via the gut-brain axis, alleviating depressive symptoms [58,59,60]. On the other hand, the development of depression is closely linked to dysfunction of the gut-brain axis. Reports indicate that depressive patients have a marked reduction in anti-inflammatory butyrate-producing bacteria within the Firmicutes phylum, such as Roseburia and Faecalibacterium, along with certain probiotic strains from Bacteroidetes (such as Prevotella) and Proteobacteria [61–62]. Increasing dietary microorganism intake may help maintain gut microbiota diversity and regulate the production of gut-derived metabolites associated with depression, such as tryptophan, kynurenic acid, and indole. These metabolites influence neurotransmitter synthesis, release, and signaling, thereby modulating amino acid metabolism in the brain and improving nervous system function [63,64,65]. Additionally, they regulate immune responses, inflammation pathways, and the permeability of the gut and blood-brain barriers, potentially slowing the progression of depression. Furthermore, higher dietary microorganism intake may enhance the communication between gut microbiota and intestinal neurons or glial cells, influencing the gut-brain axis to alleviate depressive symptoms [66]. These potential mechanisms and related findings provide important theoretical and empirical support for the scientific validity and mechanistic explanation of this study’s results.

In summary, interventions with dietary microorganisms and probiotics offer a potential dual - therapeutic approach. They can not only improve hypertension but also inhibit the mortality risk mediated by depression in the hypertensive population. Therefore, it is necessary to recommend several common foods rich in high - levels of dietary live bacteria. These foods include, but are not limited to [67]: traditional fermented dairy products (such as yogurt containing Lactobacillus bulgaricus and kefir containing Lactobacillus kefiranofaciens), plant - fermented products (such as kimchi, pickles, olives containing Lactobacillus plantarum and natto containing Bacillus subtilis natto), functional fermented beverages (such as kombucha containing acetic acid bacteria and koumiss containing lactic acid bacteria), natural live - bacteria foods (such as Lactobacillus mellifer in raw honey and Lactococcus in raw cheese), and specially cultivated foods (such as endophytes in alfalfa sprouts and cocoa microbiota in fermented cocoa beans). These foods rich in dietary live bacteria contain so-called psychobiotics and microbiota that can improve the metabolism related to cardiovascular diseases [68–69]. Thus, the selection of appropriate dietary live bacteria is of great significance for improving the long - term prognosis, physical and mental health of the population.

Although there are existing studies [70,71,72,73,74,75] that have explored the relationships between dietary live bacteria intake and diabetes, metabolic syndrome, heart health, as well as cognitive function and depression using public databases, to the best of our knowledge, there are relatively few studies on the relationship between hypertension and depression. Most studies have not jointly analyzed hypertension and depression, and rarely have they addressed the long - term prognosis of the hypertensive population. Therefore, in the existing literature, there is a lack of further explanation regarding the prognosis of the co - morbidity population of hypertension and depression. For this reason, we conducted this study to provide evidence for the conclusion that dietary microorganisms can improve the long - term prognosis of the hypertensive and depressed population. This study can be considered to have several advantages. We were the first to explore and successfully verify, using a public database, that an adequate intake of dietary live microorganisms may counteract the effect of depression on the mortality risk in the hypertensive population. In addition, in this study, the combined analysis of dietary microorganisms and depression showed a positive statistical significance in all - cause mortality risk, and the intake of dietary microorganisms had a significant trend in improving the cardiovascular mortality risk in the hypertensive population with depression. Therefore, the results of our study are expected to provide a new clinical guidance basis and recommendations for the hypertensive and depressed population.

However, it must be acknowledged that this study also has certain limitations. First, the classification of dietary live microorganisms was derived from expert discussions. Although this method has been cited in many literatures, due to the lack of precise calculation of the number of microorganisms on food, this classification method may have introduced some errors. Second, the dietary data in NHANES were collected through questionnaires. In this case, individual responses may often lead to biases in food statistics due to forgetfulness. Meanwhile, the PHQ9 depression diagnostic scale is a self-rating scale, and the filling process may be affected by the subjective thoughts of patients. The actual situation of the surveyed population may not be consistent with the scores evaluated by PHQ9. Therefore, the conclusions of this study should be verified by subsequent research. In addition, there are some potential confounding factors in this study that may affect the results. Socio-economic status may influence the dietary choices of participants. The high-socioeconomic-status group may be more capable of choosing high - quality foods rich in specific microorganisms, while the low-socioeconomic-status group may have a more monotonous diet due to economic constraints. This factor may interfere with the judgment of the relationship between dietary microorganisms and the prognosis of depression and hypertension. At the same time, access to healthcare cannot be ignored. People with easier access to medical resources may have more standardized treatment and management of hypertension and depression, which may also affect the final long-term prognosis. Although this study has fully controlled and considered these factors, there may still be biases. In addition, since the population of this study was in the United States, and the American population has a different genetic background, lifestyle, medical level, and socio - economic conditions from other countries and regions, caution is needed when generalizing these results to other regions of the world. Moreover, since this study is an observational study, we can only observe an association between the supplementation of dietary microorganisms and the improvement of the long-term prognosis in the hypertensive population with depression, but we cannot clearly determine a causal relationship.

In conclusion, although this study has concluded that the supplementation of dietary microorganisms can improve the long - term prognosis of the hypertensive population with depression, more evidence is still needed to prove the link between dietary microorganisms and the improvement of the mortality risk of hypertensive patients with depression.

Conclusion

Patients with hypertension and comorbid depression may lower depression-related mortality by increasing dietary microorganism intake. Future research could conduct more thorough clinical studies to compare the relationship between dietary microorganism intake and health.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

NCHS:

National Center for Health Statistics

BMI:

Body Mass Index

NHANES:

National Health and Nutrition Examination Survey

CVD-cause:

Cardiovascular disease-caused mortality

ALL-cause:

All reasons-caused mortality

PIR:

Price-to-Income Ratio

CKD:

Chronic Kidney Disease

HR:

Hazard Ratios

CI:

Confidence Intervals

SCFAs:

short-chain fatty acids

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Acknowledgements

We acknowledge NHANES databases for providing their platforms and contributing meaningful datasets.

Funding

This study was supported by the National Natural Science Foundation of China (No. 82474494), National Key Research and Development Program of China (No. 2022YFC3500102), the Beijing Municipal Science and Technology Development Funding Program of Traditional Chinese Medicine (No. JJ-2020-69), and High Level Chinese Medical Hospital Promotion Project (No. HLCMHPP2023065). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Author notes

  1. Xuanchun Huang, Lanshuo Hu contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Guang’anmen Hospital, China Academy of Traditional Chinese Medicine, Beijing, China

    Xuanchun Huang, Jun Li, Chao Meng & Yiying Liu

  2. Xiyuan Hospital, China Academy of Traditional Chinese Medicine, Beijing, China

    Lanshuo Hu

  3. Zhangzhou Hospital of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China

    Xiaoling Xie

  4. School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China

    Xiaoqi Wei

Authors
  1. Xuanchun Huang
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  2. Lanshuo Hu
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  3. Jun Li
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  4. Xiaoling Xie
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  5. Chao Meng
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  6. Yiying Liu
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  7. Xiaoqi Wei
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Contributions

Writing the first draft of the manuscript, statistical analyses, data organization, writing review, and editing: XC Huang, LS Hu.Research, statistical analyses, and editing: XL Xie, C Meng, YY Liu, Design research, supervision, editing, review, revision of the manuscript, and funding: J Li and XQ Wei. All authors approved the final version of the manuscript.

Corresponding authors

Correspondence to Jun Li or Xiaoqi Wei.

Ethics declarations

Ethics approval and consent to participate

The study analyzed data obtained from the public database of the National Health and Nutrition Examination Survey (NHANES). Ethics approval was granted by the National Center for Health Statistics Ethics Review Committee. The research was conducted in accordance with relevant guidelines and regulations (Declaration of Helsinki). All individuals provided written informed consent before participating in the study. Details are available at https://www.cdc.gov/nchs/nhanes/irba98.htm.

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Not applicable.

Competing interests

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Huang, X., Hu, L., Li, J. et al. Dietary live microorganisms and depression-driven mortality in hypertensive patients: NHANES 2005–2018. J Health Popul Nutr 44, 117 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s41043-025-00861-y

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  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s41043-025-00861-y

Keywords

Journal of Health, Population and Nutrition

ISSN: 2072-1315

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