Front. Endocrinol.

Frontiers in Endocrinology

Front. Endocrinol.

1664-2392

Frontiers Media S.A.

10.3389/fendo.2025.1482073

Endocrinology

Original Research

Association between Helicobacter pylori infection, serum thyroid-stimulating hormone, and thyroxine in the National Health and Nutrition Examination Survey 1999–2000

Ting

¹ Lu

Shunshun

² Lin

Jieqiong

¹ Shao

Xiaona

¹ Chen

Dahua

¹ Shen

Jianwei

¹ ^*

¹ Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo, ZheJiang, China ² Department of Hospital-Acquired Infection Control, Ningbo Medical Center Lihuili Hospital, Ningbo, ZheJiang, China

Edited by: Lutz Schomburg, Charité University Medicine Berlin, Germany

Reviewed by: Sarbjeet Makkar, Washington University in St. Louis, United States

Alin Horatiu Nedelcu, Grigore T. Popa University of Medicine and Pharmacy, Romania

*Correspondence: Jianwei Shen, shenjw1184@126.com

03 02 2025

2025

1482073

17 08 2024 13 01 2025

2025

Lu, Lu, Lin, Shao, Chen and Shen

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Background

Helicobacter pylori has been increasingly implicated in extra-gastric diseases. Current evidence regarding the association between serum thyroid-stimulating hormone (TSH), thyroxine (T4), and H. pylori infection remains inconclusive. Consequently, this study aimed to explore the correlation between TSH and T4 levels and H. pylori infection in a US-based population sample.

Methods

Data from the US National Health and Nutrition Examination Survey (NHANES), comprising 971 participants aged 30–85 years from 1999 to 2000, were analyzed. Binary logistic regression was employed to analyze the correlation between H. pylori and TSH and T4 levels. The impact of TSH and T4 on H. pylori infection was further assessed using restricted cubic spline (RCS) analysis. In addition, subgroup analyses stratified by sex and age were conducted.

Results

Subjects with H. pylori seropositivity demonstrated lower serum TSH levels and higher serum T4 levels compared to those with H. pylori seronegativity. A significant positive correlation was identified between H. pylori seropositivity and T4 levels with increasing quartiles of hormonal levels in both univariate regression models (Q4 vs. Q1: OR = 1.483; 95% CI, 1.033–2.129) and multivariate regression models (Q4 vs. Q1: OR = 1.004; 95% CI, 0.981–1.026). Conversely, a negative correlation was observed between H. pylori seropositivity and TSH levels with increasing quartiles of hormonal levels in univariate regression models (Q4 vs. Q1: OR = 0.579; 95% CI, 0.403–0.831) and in multivariate regression models (Q4 vs. Q1: OR = 0.580; 95% CI, 0.389–0.866). In stratified analyses, the adjusted association of serum T4 levels with H. pylori seropositivity was statistically significant among men (T4: Q4 vs. Q1: OR = 2.253; 95% CI, 1.311–3.873), age over 68 years in TSH levels (Q4 vs. Q1: OR = 0.434; 95% CI, 0.206–0.911), and age 41–54 years in T4 levels (Q4 vs. Q1: OR = 4.965; 95% CI, 2.071–11.903). RCS analysis revealed a non-linear relationship between TSH levels and H. pylori infection. Notably, when TSH < 0.98 IU/ml, the likelihood of H. pylori infection significantly increased.

Conclusions

Lower TSH and higher T4 levels were associated with H. pylori infection, particularly among men and elderly individuals.

Helicobacter pylori infection thyroid stimulating hormone thyroxine NHANES CDC

Science and Technology Innovation 2025 Major Project of Ningbo10.13039/501100017549

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Thyroid Endocrinology

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1 Introduction

Helicobacter pylori is a bacterium that preferentially colonizes in the gastric epithelium, often causing a spectrum of digestive disease, including peptic ulcer, chronic gastritis, and even gastric cancer. It has been reported that approximately half of the global population is infected with H. pylori (1), with a prevalence rate of approximately 35.6% in the US (2). Furthermore, numerous extra-gastric diseases have been proven to be associated with H. pylori infection, such as dermatosis, thyroid diseases, and metabolic, cardiovascular, and neurological diseases (3–5).

Thyroxine (T4) is a thyroid hormone (TH) synthesized and secreted by the thyroid gland (6). The regulation of THs is governed by the complex hypothalamic–pituitary–thyroid (HPT) axis. Thyroid-stimulating hormone (TSH), produced by the anterior pituitary gland, promotes the synthesis and release of THs, primarily through negative feedback mechanisms within the HPT axis (7). Evidence indicates that H. pylori infection plays a pivotal role in thyroid disease (8), particularly autoimmune thyroid diseases (ATDs), owing to its ability to mimic the antigenic profile present on thyroid cell membranes (9). Vincenzo Bassi et al. discovered a heightened prevalence of H. pylori exclusively among patients with hyperthyroid Graves’ disease (GD), in contrast to those with Hashimoto thyroiditis (HT) (10). Additionally, De Luis et al. reported markedly elevated levels of anti-H. pylori immunoglobulin G antibodies in patients with subclinical hyperthyroidism, compared to the control cohort (11). Furthermore, a recent prospective study highlighted a substantial association between H. pylori infection and the likelihood of subclinical hyperthyroidism in Chinese women, independent of dietary factors (12). Both TSH and T4 are considered sensitive biomarkers for evaluating thyroid function, reflecting conditions of either hypothyroidism or hyperthyroidism (13). At present, the relationship between H. pylori infection and plasma levels of TSH and T4 in the general population remains insufficiently investigated and contentious (14–16).

Since the T4 data were incorporated in October 2023, it is now particularly intriguing to explore the relationship between TSH, T4 levels, and H. pylori infection based on data from the 1999–2000 National Health and Nutrition Examination Survey (NHANES).

2 Materials and methods 2.1 Study design and sample

NHANES is a publicly accessible database managed by the Centers for Disease Control and Prevention (CDC), providing extensive data regarding the health and nutritional status of the non-institutionalized U.S population. The survey encompasses information derived from questionnaires, demographic profiles, laboratory tests, and physical examinations (17, 18). The data analyzed in this study were form the 1999–2000 NHANES cycles, encompassing participants who had both H. pylori infection and measurements of plasma TSH and T4 levels, with T4 data being added to the database in October 2023.

The exclusion criteria were as follows: (1) individuals aged <30 or >85 years; (2) missing data for H. pylori serology, TSH, or T4 levels; and (3) individuals with thyroid disease or taking thyroid medications. Participants possessing relevant laboratory data and demographic variables of interest were incorporated into this investigation, culminating in a total sample size of 971 individuals aged between 30 and 85 years old. The schematic representation of the participant selection process is illustrated in Figure 1 .

Figure 1

The flowchart of sample selection.

2.2 <italic>Helicobacter pylori</italic> status

In accordance with the NHANES protocol (19), H. pylori-specific immunoglobulin G (IgG) levels were quantified utilizing the H. pylori IgG enzyme-linked immunosorbent assay (ELISA) developed by Wampole Laboratories (Granbury, N) (20). Standard ELISA cutoff values were applied to classify participants as seropositive [optical density (OD) value ≥1.1] or seronegative (OD value < 0.9) for H. pylori. Indeterminate results (OD values between 0.9 and 1.1) were excluded to avoid potential biases in the statistical analysis of this investigation (21).

2.3 Thyroid-stimulating hormone and thyroxine

The dependent variable analyzed in this study was H. pylori seropositivity, while the primary independent variables of interest were plasma levels of TSH and T4. Both serum TSH and T4 were sourced from the NHANES laboratory dataset, designated as LAB18T4, which was updated in October 2023. Thyroid medications have been identified in the prescription drug medication document.

2.4 Covariates

The covariates examined in this research encompass age, gender, race, education level, body mass index (BMI), smoking behavior, alcohol behavior, and homocysteine levels. These variables were selected based on existing evidence linking them to both H. pylori serostatus and thyroid function (18, 21, 22). Among the covariates, age, TSH, T4, and homocysteine were categorized as continuous variables, while sex, race, education level, BMI, smoking behavior, and alcohol behavior were classified as categorical variables.

2.5 Statistical analyses

For continuous variables, independent t-test or Mann–Whitney test was employed to analyze the differences between groups. Depending on the normality of distribution, continuous variables were presented as mean ± SD; otherwise, they were presented as Median. Categorical variables were assessed using the chi-square test and reported as counts and percentages. Levels of TSH and T4 were categorized into quartiles (Q1 to Q4). Multiple regression analysis was conducted to identify the factors influencing TSH and T4 levels. Furthermore, the relationship between TSH, T4, and H. pylori was examined through restricted cubic spline (RCS) analysis, with knots positioned at the 5th, 35th, 65th, and 95th percentiles. Statistical analyses were carried out using SPSS (version 26.0) and R software (version 4.1.3), with a significance threshold set at p < 0.05, where both the p for overall and the p for non linear relationship in RCS were less than 0.05.

3 Results 3.1 Characteristics of included subjects

A total of 971 participants were included in this study, with 498 classified as H. pylori IgG seropositive and 473 as H. pylori IgG seronegative. Notable differences were detected between the two groups (p < 0.05) in terms of age, race, educational level, and serum TSH and T4 levels. The baseline characteristics of the study subjects are detailed in Table 1 .

Table 1

Baseline characteristics of the study subjects.

	H. pylori seropositive (n = 498)	H. pylori seronegative (n = 473)	p-value
Age (years)	56.0 (42.0–68.0)	52.0 (39.0–67.5)	0.037
Sex			0.168
Male	260 (52.2%)	226 (47.8%)
Female	238 (47.8%)	247 (52.2%)
Race			<0.001
Mexican American	197 (39.5%)	55 (11.6%)
Other Hispanic	39 (7.8%)	9 (1.9%)
Non-Hispanic white	132 (26.5%)	335 (70.8%)
Non-Hispanic black	111 (22.2%)	65 (13.7%)
Other races	19 (3.8%)	9 (1.9%)
Educational level			<0.001
Less than high school	277 (55.6%)	108 (22.8%)
High school	92 (18.4%)	120 (25.3%)
More than high school	128 (5.7%)	244 (51.5%)
Others	1 (0.2%)	1 (0.2%)
BMI	27.78 (24.58–31.59)	27.27 (24.06–31.96)	0.317
Homocysteine (μmol/L)	8.14 (6.45–10.20)	7.69 (6.29–9.88)	0.055
Serum TSH (IU/mL)	1.48 (1.02–2.15)	1.64 (1.13–2.43)	0.008
Serum T4 (nmol/L)	97.80 (84.90–113.30)	92.70 (83.70–108.10)	0.013
Smoking behavior			0.21
Never	203 (40.8%)	194 (41.0%)
Some days	113 (22.7%)	116 (24.5%)
Every day	182 (36.5%)	163 (34.5%)
Alcohol behavior			0.749
Yes	332 (66.7%)	322 (68.1%)
No	166 (33.3%)	151 (31.9%)

Other race/ethnicity includes all race/ethnicity other than Mexico-American, non-Hispanic white, and black. BMI, body mass index; TSH, thyroid-stimulating hormone; T4, thyroxine. Bold represents statistically significant.

3.2 Association between <italic>H. pylori</italic> seropositivity and TSH and T4 3.2.1 Multiple regression model

The outcomes of different multivariate linear regression models are summarized in Tables 2 , 3 : Model 1 is unadjusted, model 2 is adjusted for age and sex, and model 3 is further adjusted for race and educational level.

Table 2

Association of thyroid-stimulating hormone level with Helicobacter pylori seropositivity.

TSH	Model 1		Model 2		Model 3
	OR (95% CI)	p-value	OR (95% CI)	p-value	OR (95% CI)	p-value
Q1	Ref		Ref		Ref
Q2	0.731 (0.511–1.046)	0.087	0.715 (0.499–1.026)	0.068	0.701 (0.477–1.032)	0.072
Q3	0.780 (0.545–1.117)	0.175	0.758 (0.528–1.087)	0.132	0.775 (0.525–1.140)	0.195
Q4	0.579 (0.403–0.831)	0.003	0.544 (0.377–0.786)	0.001	0.580 (0.389–0.866)	0.008

Model 1: no covariates were adjusted; model 2: age and sex were adjusted; model 3: age, sex, race, and educational level were adjusted. OR, odds ratio. Q1: <1.09 mIU/L, Q2: 1.09–1.57 mIU/L, Q3: 1.57–2.30 mIU/L, Q4: >2.30 mIU/L.

Table 3

Association of thyroxine level with Helicobacter pylori seropositivity.

T4	Model 1		Model 2		Model 3
	OR (95% CI)	p-value	OR (95% CI)	p-value	OR (95% CI)	p-value
Q1	Ref		Ref		Ref
Q2	0.865 (0.601–1.245)	0.434	0.885 (0.614–1.278)	0.515	0.886 (0.597–1.316)	0.549
Q3	1.161 (0.810–1.666)	0.416	1.211 (0.840–1.747)	0.305	1.252 (0.842–1.862)	0.267
Q4	1.483 (1.033–2.129)	0.033	1.552 (1.076–2.238)	0.019	1.004 (0.981–1.026)	0.048

Model 1: no covariates were adjusted; model 2: age and sex were adjusted; model 3: age, sex, race, and educational level were adjusted. OR, odds ratio. Q1: <83.7 nmol/L, Q2: 83.7–95.2 nmol/L, Q3: 95.2–110.7 nmol/L, Q4: >110.7 nmol/L.

In the unadjusted model, a negative association was identified between H. pylori seropositivity and TSH levels across increasing quartiles of hormonal levels (Q4 vs. Q1: OR = 0.579; 95% CI, 0.403–0.831, p = 0.003). This negative relationship persisted after adjustments for confounding factors in model 2 (Q4 vs. Q1: OR = 0.544, 95% CI, 0.377–0.786; p = 0.001) and model 3 (Q4 vs. Q1: OR = 0.580, 95% CI, 0.389–0.866; p = 0.008). Conversely, a significant positive association was observed between H. pylori and T4 levels across increasing quartiles of hormonal levels (Q4 vs. Q1: OR = 1.483; 95% CI, 1.033–2.129, p = 0.033). This positive connection remained significant after adjustments for confounding factors in model 2 (Q4 vs. Q1: OR = 1.552; 95% CI, 1.076–2.238, p = 0.019) and was marginally significant in model 3 (Q4 vs. Q1: OR = 1.004; 95% CI, 0.981–1.026, p = 0.048), as presented in Table 3 .

3.2.2 Subgroup analyses

In the sex-stratified subgroup analyses, a positive correlation was discovered between the H. pylori seropositivity and T4 levels in men (Q4 vs. Q1 OR = 2.253; 95% CI, 1.311–3.873; p = 0.003). However, no significant relationship was observed between TSH levels and H. pylori seropositivity in men, as the positive correlation disappeared after adjusting for confounding variables in the multivariate regression model (Q4 vs. Q1 OR = 0.636; 95% CI, 0.340–1.188; p = 0.156). Among women, neither TSH nor T4 levels exhibited any association with H. pylori seropositivity. Detailed findings are provided in Tables 4 , 5 .

Table 4

Association of thyroid-stimulating hormone level with Helicobacter pylori seropositivity based on subgroup of sex.

Subgroup	TSH	Model 1		Model 2		Model 3
		OR (95% CI)	p-value	OR (95% CI)	p-value	OR (95% CI)	p-value
Male	Q1	Ref		Ref		Ref
	Q2	0.621 (0.373–1.035)	0.068	0.614 (0.368–1.024)	0.062	0.611 (0.339–1.013)	0.102
	Q3	0.595 (0.355–0.997)	0.049	0.584 (0.348–0.980)	0.042	0.675 (0.370–1.233)	0.202
	Q4	0.494 (0.294–0.831)	0.008	0.465 (0.273–0.792)	0.005	0.636 (0.340–1.188)	0.156
Female	Q1	Ref		Ref		Ref
	Q2	0.845 (0.508–1.406)	0.518	0.830 (0.498–1.385)	0.830	0.830 (0.449–1.436)	0.459
	Q3	1.012 (0.613–1.671)	0.963	0.974 (0.587–1.614)	0.918	1.248 (0.691–2.256)	0.463
	Q4	0.672 (0.405–1.116)	0.125	0.633 (0.379–1.058)	0.081	0.799 (0.440–1.452)	0.461

Table 5

Association of thyroxine level with Helicobacter pylori seropositivity based on subgroup of sex.

Subgroup	T4	Model 1		Model 2		Model 3
		OR (95% CI)	p-value	OR (95% CI)	p-value	OR (95% CI)	p-value
Male	Q1	Ref		Ref		Ref
	Q2	0.917 (0.570–1477)	0.722	0.937 (0.580–1.514)	0.791	1.169 (0.671–2.037)	0.582
	Q3	1.258 (0.773–2.047)	0.356	1.303 (0.795–2.135)	0.294	1.617 (0.913–2.864)	0.100
	Q4	2.184 (1.278–3.734)	0.004	2.253 (1.311–3.873)	0.003	2.061 (1.093–3.887)	0.025
Female	Q1	Ref		Ref		Ref
	Q2	0.819 (0.459–1.461)	0.499	0.812 (0.454–1.454)	0.812	0.576 (0.298–1.112)	0.100
	Q3	1.097 (0.626–1.924)	0.746	1.142 (0.648–2.012)	0.645	0.938 (0.493–1.783)	0.844
	Q4	1.211 (0.702–2.088)	0.491	1.278 (0.737–2.216)	0.382	0.848 (0.447–1.610)	0.614

In the age-stratified subgroup analyses, a negative correlation was identified between H. pylori seropositivity and TSH levels among participants aged over 68 years (Q4 vs. Q1: OR = 0.434; 95% CI, 0.206–0.911; p = 0.027). Furthermore, no significant association was observed between TSH levels and H. pylori seropositivity in other age groups, as detailed in Table 6 . Additionally, there was a positive association between H. pylori seropositivity and T4 levels among participants aged 41–54 years (Q4 vs. Q1: OR = 4.965; 95% CI, 2.071–11.903; p < 0.001). However, T4 levels showed no significant relationship with H. pylori seropositivity in other age groups, as outlined Table 7 .

Table 6

Association of thyroid-stimulating hormone level with Helicobacter pylori seropositivity based on subgroup of age.

Subgroup	TSH	Model 1		Model 2		Model 3
		OR (95% CI)	p-value	OR (95% CI)	p-value	OR (95% CI)	p-value
<41	Q1	Ref		Ref		Ref
	Q2	0.729 (0.367–1.448)	0.366	0.730 (0.367–1.452)	0.730	0.409 (0.176–0.950)	0.038
	Q3	0.759 (0.397–1.591)	0.517	0.796 (0.397–1.593)	0.796	0.799 (0.339–1.880)	0.606
	Q4	0.622 (0.284–1.363)	0.235	0.621 (0.283–1.362)	0.235	0.658 (0.248–1.746)	0.401
41–54	Q1	Ref		Ref		Ref
	Q2	0.806 (0.403–1.612)	0.541	0.804 (0.397–1.628)	0.544	1.551 (0.652–3.691)	0.321
	Q3	0.731 (0.358–1.493)	0.731	0.738 (0.357–1.527)	0.413	1.304 (0.529–3.212)	0.564
	Q4	0.505 (0.243–1.046)	0.066	0.570 (0.282–0.800)	0.139	1.198 (0.472–3.042)	0.704
54–68	Q1	Ref		Ref		Ref
	Q2	1.031 (0.497–2.317)	0.953	1.041 (0.501–2.161)	0.914	0.911 (0.381–2.178)	0.835
	Q3	0.737 (0.356–1.526)	0.411	0.740 (0.357–1.533)	0.418	0.518 (0.210–1.279)	0.154
	Q4	0.650 (0.312–1.351)	0.248	0.811 (0.488–1.349)	0.420	0.712 (0.281–1.803)	0.474
>68	Q1	Ref		Ref		Ref
	Q2	0.383 (0.171–0.861)	0.020	0.391 (0.174–0.880)	0.023	0.428 (0.178–1.030)	0.058
	Q3	0.722 (0.333–1.568)	0.411	0.719 (0.331–1.564)	0.406	1.153 (0.490–2.718)	0.744
	Q4	0.422 (0.202–0.884)	0.022	0.434 (0.206–0.911)	0.027	0.645 (0.283–1.470)	0.297

Table 7

Association of thyroxine level with Helicobacter pylori seropositivity based on subgroup of age.

Subgroup	T4	Model 1		Model 2		Model 3
		OR (95% CI)	p-value	OR (95% CI)	p-value	OR (95% CI)	p-value
<41	Q1	Ref		Ref		Ref
	Q2	0.436 (0.190–0.997)	0.049	0.434 (0.190–0.995)	0.049	0.288 (0.106–0.784)	0.015
	Q3	1.714 (0.792–3.712)	0.172	1.730 (0.797–3.758)	0.166	1.395 (0.539–3.612)	0.493
	Q4	1.062 (0.503–2.239)	0.875	0.921 (0.530–1.602)	0.835	0.749 (0.290–1.933)	0.550
41–54	Q1	Ref		Ref		Ref
	Q2	2.500 (1.068–5.849)	0.035	2.974 (1.235–7.162)	0.015	2.711 (0.968–7.596)	0.058
	Q3	2.049 (0.911–4.610)	0.083	2.317 (1.006–5.336)	0.048	2.171 (0.782–6.030)	0.137
	Q4	4.083 (1.759–9.477)	0.001	4.965 (2.071–11.903)	<0.001	3.986 (1.346–11.798)	0.013
54–68	Q1	Ref		Ref		Ref
	Q2	0.605 (0.292–1.256)	0.178	0.633 (0.302–1.324)	0.224	0.618 (0.252–1.513)	0.292
	Q3	0.646 (0.315–1.324)	0.233	0.683 (0.329–1.419)	0.307	0.853 (0.353–2.061)	0.724
	Q4	1.059 (0.515–2.178)	0.876	1.157 (0.546–2.454)	0.703	0.924 (0.360–2.373)	0.870
>68	Q1	Ref		Ref		Ref
	Q2	1.026 (0.537–1.961)	0.937	0.975 (0.506–1.877)	0.939	1.134 (0.558–2.307)	0.728
	Q3	1.205 (0.590–2.459)	0.609	1.120 (0.542–2.316)	0.759	1.269 (0.584–2.759)	0.547
	Q4	1.564 (0.770–3.178)	0.216	1.446 (0.702–2.979)	0.318	1.306 (0.590–2.890)	0.510

3.2.3 Non-linear relationship between TSH, T4, and <italic>H. pylori</italic> infection

An RCS model was employed to assess the association between TSH levels and H. pylori infection. As illustrated in Figure 2 , when TSH levels fall below 0.98 IU/mL, the risk of H. pylori infection rises significantly (p < 0.05). Conversely, there was no linear relationship between T4 levels and H. pylori infections.

Figure 2

The restricted cubic spline curve for the relationship between serum TSH levels and H. pylori infection. The blue lines represent odds ratios, and blue areas represent 95% confidence intervals.

4 Discussion

This study utilized newly updated NHANES data to explore the relationship between TSH and T4 levels and H. pylori infection. In summary, H. pylori seropositivity demonstrated a positive correlation with T4 levels and a negative correlation with TSH levels. In stratified analyses, the adjusted association between serum T4 levels and H. pylori seropositivity was statistically significant in men but not in women, with significant correlations observed for serum TSH in participants over 68 years of age and for T4 in those aged 41–45 years.

As is widely acknowledged, thyroid function is composed of TSH and T4, with these serum markers often exhibiting a negative correlation. Our research identified variations in TSH and T4 levels between populations positive and negative for H. pylori. The non-linear connection revealed an enormous rise in the likelihood of H. pylori infection when TSH levels < 0.98 IU/mL. This suggests that individuals exhibiting hyperthyroid tendencies are more susceptible to H. pylori infection, corroborating findings from prior studies (10).

H. pylori testing should be considered for individuals undergoing treatment with medications known to be affected by this infection, such as T4, as outlined in the Houston Consensus (23). Therefore, this suggests an implied relationship between H. pylori infection and thyroid function. Nonetheless, the impact of thyroid function disorders, including hyperthyroidism or hypothyroidism, on H. pylori infection remains a contentious issue. Larizza et al. demonstrated that H. pylori could provoke an immune response against thyroid cells (24). A notable association has also been observed between Cag-A-positive H. pylori strains and GD, regardless of the patients’ hormonal status (25). The association may be attributed to cross-reactivity between antibodies against the H. pylori Cag-A protein and the follicular cells of the thyroid gland (26). Additionally, conflicting findings from other research have indicated a positive correlation between H. pylori infection and autoimmune atrophic thyroiditis (27, 28).

The mechanisms by which elevated T4 levels and suppressed TSH levels heighten the susceptibility to H. pylori infection remain incompletely understood; however, several lines of evidence may shed light on this relationship. Firstly, the discovery of a homologous 11-residue peptide shared by both gastric parietal cell antigens and thyroid peroxidase suggests a common epitope (29), implying that antibodies generated during H. pylori infection may cross-react with thyroid antigens, potentially contributing to hyperthyroidism (30). Secondly, studies have shown a strong correlation between IgG anti-H. pylori antibodies and thyroid autoantibodies, along with a reduction in thyroid autoantibody levels following the successful eradication of H. pylori infection (31). Thirdly, previous investigations have demonstrated that H. pylori strains can express fucosylated Lewis determinants, which are commonly found in various host tissues and may trigger an autoimmune response that could impair thyroid function (32). Typically, thyroid diseases, particularly ATDs, are influenced by a variety of autoimmune mechanisms. It has been reported that H. pylori infection plays a role in the pathogenesis of HT, the leading cause of hypothyroidism (28). In addition, in GD, humoral autoimmunity characterized by a TH2 profile is prevalent. Once infected with H. pylori, cytokines such as interleukin (IL)-4, IL-5, and IL-6 are activated, initiating a cascade of humoral immune responses that may modify the expression of adhesion molecules on the gastric mucosa, thereby contributing to the hyperthyroidism observed in GD (10, 33). The mechanism is believed to be associated with molecular mimicry between H. pylori antigens and thyroid constituents. Collectively, these findings offer compelling explanations for the observed correlation between H. pylori infection and hyperthyroidism.

A notable correlation was found between persistent H. pylori infection and ATDs in female patients, regardless of thyroid gland functional status. Specifically, this association was observed in relation to both HT and GD across multiple studies (10, 12), whereas no such connection was noted for non-autoimmune thyroid disorders. Although this association was primarily observed in women, a trend suggesting a similar relationship was noted in men (34). Because of the limitations of the NHANES database, the present study was unable to include thyroid autoantibodies such as thyroglobulin antibody (TGAb) and thyroid peroxidase antibodies (TPOAbs), which may have resulted in a weakened association between H. pylori seropositivity and TSH levels as well as T4 levels within gender cohorts.

Previous studies have suggested that the successful colonization of H. pylori in the gastric environment is influenced by age-related physiological factors and host characteristics, with the incidence of H. pylori-related diseases increasing with age (35, 36), a finding consistent with our results. Furthermore, additional factors such as socioeconomic status, geographical location, and ethnicity may also contribute to the rates of H. pylori infection (37). Breckan et al. reported that the prevalence of H. pylori is age-dependent, rising from adolescence and reaching its peak between the ages of 60 and 70 years (38).

It has to be recognized that there are several limitations in this study. First, H. pylori infection was defined based on serological testing, which cannot distinguish between past and present infections. Second, the NHANES 1999–2000 dataset lacked certain relevant information, such as TGAb and TPOAb, which weakens the association between H. pylori and thyroid autoimmunity, thus hindering a more thorough exploration of the underlying mechanisms. Should future NHANES updates include these data, more detailed classification comparisons could be conducted again in the future. Third, as a cross-sectional study, it does not allow for the establishment of causative relationships between TSH and T4 levels and H. pylori seropositivity, nor does it provide temporal data to differentiate between past and present H. pylori infections. Further longitudinal studies are needed to make interpretations of observed associations in the future. Lastly, while we accounted for the influence of certain medications, other factors, such as long-term contraceptive use in women, may affect thyroid function (39), as well as dietary factors like “high-salt” intake (40) or a high dietary inflammatory index (41), which are likely to influence the prevalence of H. pylori infection.

5 Conclusion

Overall, serum TSH and T4 levels were found to be associated with the risk of H. pylori infection, particularly among men, individuals with hyperthyroidism, and elderly adults. These people should pay close attention to H. pylori screening, as H. pylori infection is closely related to gastric cancer.

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics statement

The studies involving humans were approved by Ethics Committee of Ningbo Medical Center Li Huili Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The ethics committee/institutional review board waived the requirement of written informed consent for participation from the participants or the participants’ legal guardians/next of kin because the data were obtained from public databases and were exempted from ethical review by the Ethics Committee of Ningbo Medical Center Li Huili Hospital.

Author contributions

TL: Writing – review & editing, Data curation, Formal Analysis, Investigation, Writing – original draft. SL: Data curation, Formal Analysis, Writing – review & editing. JL: Data curation, Writing – original draft. XS: Data curation, Writing – review & editing. DC: Data curation, Writing – review & editing. JS: Conceptualization, Writing – review & editing.

Funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Ningbo Science and Technology Innovation 2025 Major Special Project of China (No. 2023Z159).

Conflict of interest

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.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References 1 Zamani

Ebrahimtabar

Miller

W.H

Alizadeh-Navael

Shokri-Shirvanl

. Systematic review with meta analysis: the worldwide prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther. (2018) 47:868–76. doi: 10.1111/apt.2018.47.issue-7 2 Burucoa

Axon

. Epidemiology of Helicobacter pylori infection. Helicobacter. (2017) 22:1–5. doi: 10.1111/hel.2017.22.issue-S1 3 Astl

Sterzl

. Activation of helicobacter pylori causes either autoimmune thyroid diseases or carcinogenesis in the digestive tract. Physiol Res. (2015) 64:S291–301. doi: 10.33549/physiolres 4 Kucukazman

Yeniova

Dal

Yavuz

. Helicobacter pylori and cardiovascular disease. Eur Rev Med Pharmacol Sci. (2015) 19:3731–41. 5 Wang

Cao

Z-M

Zhang

L-L

Dai

X-C

Liu

Z-J

Zeng

Y-X

. Helicobacter pylori and autoimmune diseases: Involing multiple systems. Front Immunol. (2022) 13:833424. doi: 10.3389/fimmu.2022.833424 6 Mullur

Liu

Brent

. Thyroid hormone regulation of metabolism. Physiol Rev. (2014) 94:355–82. doi: 10.1152/physrev.00030.2013 7 Chiamolera

Wondisford

. Minireview: thyrotropin-releasing hormone and the thyroid hormone feedback mechanism. Endocrinology. (2009) 150:1091–6. doi: 10.1210/en.2008-1795 8 Wang

Zhu

Wang

Zhu

. Interaction between gene a-positive helicobacter pylori and human leukocyte antigen II alleles increase the risk of graves disease in Chinese han population: An association study. Gene. (2013) 531:84–9. doi: 10.1016/j.gene.2013.07.069 9 Hou

Sun

Zhang

Wang

Guo

. Meta-analysis of the correlation between helicobacter pylori infection and autoimmune thyroid diseases. Oncotarget. (2017) 8:115691–700. doi: 10.18632/oncotarget.22929 10 Bassi

Marino

Iengo

Fattoruso

Santinelli

. Autoimmune thyroid diseases and Helicobacter pylori: The correlation is present only in Graves’s disease. World J Gastroenterol. (2012) 18:1093–7. doi: 10.3748/wjg.v18.i10.1093 11 Shi

Liu

Zhou

Zhang

. Associations of helicobacter pylori infection and cytotoxin-associated gene a status with autoimmune thyroid diseases: a meta-analysis. Thyroid. (2013) 23:1294–300. doi: 10.1089/thy.2012.0630 12 Zhang

Hai

Wang

Zhu

Meng

. Helicobacter pylori infection increase the risk of subclinical hyperthyroidism in middle-aged and elderly women independent of dietary factors: Results from the Tianjin chronic low-grade systemic inflammation and health cohort study in China. Front Nutr. (2023) 10:1002359. doi: 10.3389/fnut.2023.1002359 13 Fan

Liu

Zhang

Shi

Zhang

. Thyroid stimulating hormone levels are associated with genetically predicted nonalcoholic fatty liver disease. J Clin Endocrinol Metab. (2022) 107:2522–9. doi: 10.1210/clinem/dgac393 14 Skelin

Lucijanić

Amidžić Klarić

Resič

Bakula

LiberatiČizmek

. Factors affecting gastrointestinal absorption of levothyroxine: A review. Clin Ther. (2017) 39:378–403. doi: 10.1016/j.clinthera.2017.01.005 15 Triantafifillidis

Georgakopoulos

Gikas

Merikas

Peros

Sofroniadou

. Relation between helicobacter pylori infection, thyroid hormone levels and cardiovascular risk factors on blood donors. Hepatogastroenterology. (2003) 50:cccxviii–cccxx. 16 Tomasi

Dore

Fanciulli

Sanciu

Realdi

Delitala

. Is there anything to the reported association between helicobacter pylori infection and autoimmune thyroiditis? Dig Dis Sci. (2005) 50:385–8. doi: 10.1007/s10620-005-1615-z 17 Prevention CfDCa . National health and nutrition examination survey: centers for disease control and prevention (2020). Available online at: https://www.cdc.gov/nchs/nhanes/index.htm (Accessed 05 Apr 2021). 18 Huang

Liu

Wang

. The association between helicobacter pylori seropositivity and bone mineral density in adults. Med Inflammation. (2022) 2022:2364666. doi: 10.1155/2022/2364666 19 Centers for Disease Control and Prevention . National Health and Nutrition Examination Survey 1999–2001 Data Documentation, Codebook, and Frequencies – H. pylori . Available online at: https://wwwn.cdc.gov/Nchs/Nhanes/1999-2000/LAB11.htm (Accessed 1 April 2024). 20 Berrett

Gale

Erickson

Brown

Hedges

. Folate and inflammatory markers moderate the association between helicobacter pylori exposure and cognitive function in US adults. Helicobacter. (2016) 21:471–80. doi: 10.1111/hel.12303 21 Meier

HCS

Miller

Dinse

Weinberg

Cho

Parks

. Helicobacter pylori seropositivity is associated with antinuclear antibodies in US adults, NHANES 1999-2000. Epidemiol Infect. (2020) 148:e20. doi: 10.1017/S0950268820000126 22 Huang

Xie

Niu

. The relation between helicobacter pylori immunoglobulin G seropositivity and leukocyte telomere length in US adults from NHANES 1999-2000. Helicobacter. (2020) 25:e12760. doi: 10.1111/hel.12760 23 El-Serag

Kao

Kanwal

Gilger

LoVecchio

Moss

. Houston Consensus conference on testing for helicobacter pylori infection in the United States. Clin Gastroenterol Hepatol. (2018) 16:992–1002. doi: 10.1016/j.cgh.2018.03.013 24 Larizza

Calcaterra

Martinetti

Negrini

De Silvestri

Cisternino

. Helicobacter pylori infection and autoimmune thyroid disease in young patients: the disadvantage of carrying the human leukocyte antigenDRB1*0301 allele. J Clin Endocrinol Metab. (2006) 91:176–9. doi: 10.1210/jc.2005-1272 25 Bassi

Santinelli

Iengo

Romano

. Identification of a correlation between Helicobacter pylori infection and Graves’ disease. Helicobacter. (2010) 15:558–62. doi: 10.1111/j.1523-5378.2010.00802.x 26 Figura

Di Cairano

Moretti

Lacoponi

Santucci

Bernardini

. Helicobacter pylori infection and autoimmune thyroid diseases: the role of virulent strains. Antibiotics. (2019) 9:12. doi: 10.3390/antibiotics9010012 27 Papamichael

Papaioannou

Karga

Roussos

Mantzaris

. Helicobacter pylori infection and endocrine disorders: is there a link? World J Gastroenterol. (2009) 15:2701–7. doi: 10.3748/wjg.15.2701 28 De Luis

Varela

de la Calle

Cantón

de Argila

San Roman

. Helicobacter pylori infection is markedly increased in patients with autoimmune atrophic thyroiditis. J Clin Gastroenterol. (1998) 26:259–63. doi: 10.1097/00004836-199806000-00008 29 Elisei

Mariotti

Swillens

Vassart

Ludgate

. Studies with recombinant autoepitopes of thyroid peroxidase: evidence suggesting an epitope shared between the thyroid and the gastric parietal cell. Autoimmunity. (1990) 8:65–70. doi: 10.3109/08916939008998434 30 Choi

Kim

Jang

Jeon

Kim

. Association between thyroid autoimmunity and helicobacter pylori infection. Korean J Intern Med. (2017) 32:309–13. doi: 10.3904/kjim.2014.369 31 Bertalot

Montresor

Tampieri

Spasiano

Pedroni

Milanesi

. Decrease in thyroid autoantibodies after eradication of helicobacter pylori infection. Clin Endocrinol. (2004) 61:650–2. doi: 10.1111/j.1365-2265.2004.02137.x 32 Wirth

Yang

Karita

Blaser

. Expression of the human cell surface glycoconjugates Lewis x and Lewis y by helicobacter pylori isolates is related to cagA status. Infect Immun. (1996) 64:4598–605. doi: 10.1128/iai.64.11.4598-4605.1996 33 Roura-Mir

Catálfamo

Sospedra

Alcalde

PujolBorrell

Jaraquemada

. Single-cell analysis of intrathyroidal lymphocytes shows differential cytokine expression in Hashimoto’s and Graves’ disease. Eur J Immunol. (1997) 27:3290–302. doi: 10.1002/eji.1830271228 34 Dore

Fanciulli

Manca

Pes

. Association of helicobacter pylori infection with autoimmune thyroid disease in the female sex. J Clin Med. (2023) 12:5150. doi: 10.3390/jcm12155150 35 Huang

Sweeney

Sigal

Zhang

Remington

Cantrell

. Chemodetection and destruction of host urea allows helicobacter pylori to locate the epithelium. Cell Host Microbe. (2015) 18:147–56. doi: 10.1016/j.chom.2015.07.002 36 Goh

Chan

Shiota

Yamaoka

. Epidemiology of helicobacter pylori infection and public health implications. Helicobacter. (2011) 16:1–9. doi: 10.1111/j.1523-5378.2011.00874.x 37 Sreeja

T-D

Eom

S-H

Shivappa

Hebert

J-R

. Association between the dietary inflammatory index and gastric disease risk: findings from a Korean population-based cohort study. Nutrients. (2022) 14:2662. doi: 10.3390/nu14132662 38 Breckan

Paulssen

Asfeldt

Kvamme

J-M

Straume

Florholmen

. The all-age prevalence of helicobacter pylori infection and potential transmission routes. A population-based study. Helicobacter. (2016) 21)6:586–95. doi: 10.1111/hel.12316 39 Qiu

Xing

Zhu

. Birth control pills and risk of hypothyroidism: a cross-sectional study of the national health and nutrition examination survey, 2007-2012. BMJ Open. (2021) 11:e46607. doi: 10.1136/bmjopen-2020-046607 40 Shu

Zheng

P-F

Zhang

X-Y

Feng

Y-L

. Dietary patterns and Helicobacter pylori infection in a group of Chinese adults ages between 45 and 59 years old. Medicine. (2019) 98:2(e14113). doi: 10.1097/MD.0000000000014113 41 Xiong

Diao

Wen

Meng

Gao

. Association of dietary inflammatory index with helicobacter pylori infection and mortality among US population. J Trans Med. (2023) 21:538. doi: 10.1186/s12967-023-04398-8

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