ABSTRACT
Helicobacter pylori infection is the cause of 90% of non-cardia gastric cancer. Several dietary elements have been identified as possible contributors to H. pylori infection and its advancement through various pathways. Based on the anti-inflammatory and anti-microbial effects of a diet low in omega-6 and high in omega-3 polyunsaturated fatty acids (PUFAs), this study aimed to assess the ratio of dietary omega-6 to omega-3 PUFAs and the risk of developing H. pylori. The present case-control study was conducted on 150 cases with H. pylori infection and 302 controls. The omega-6 to omega-3 ratio was calculated using food intake information sourced from a validated food frequency questionnaire. Physical activity and demographic data were collected through a related questionnaire. The association between the odds of H. pylori infection and the omega-6 to omega-3 ratio was evaluated using logistic regression models. A p value < 0.05 was considered statistically significant. The findings revealed that individuals in the third tertile had significantly higher odds of H. pylori (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.30–3.40) in the crude model. Furthermore, even after adjusting the potential confounders including sex, age, body mass index, physical activity, energy intake, alcohol, and smoking status, this association remained significant (fully adjusted model: OR, 2.00; 95% CI, 1.17–3.34). Our study revealed a higher ratio of omega-6 to omega-3 was related to a higher likelihood of H. pylori infection. Therefore, it is advisable to maintain a balanced intake of PUFAs in the diet.
-
Keywords: Helicobacter pylori; Unsaturated fatty acids; Omega-6; Omega-3; Inflammation
INTRODUCTION
Gastric cancer ranks fifth in common malignancies worldwide and is the fourth most prevalent cause of cancer-related mortality, primarily affecting older adults [
1].
Helicobacter pylori infection is attributed to 90% of non-cardiac cancers [
2]. According to the International Agency for Research on Cancer,
H. pylori is a type I carcinogenic agent and is believed to be responsible for 80% of all stomach cancers due to its effects on inflammation, peptic ulcer, chronic gastritis, and primary gastric lymphoma [
3]. Research conducted in Latin America, Canada, Iran, China, Russia, and Jordan has revealed a high outbreak of
H. pylori infection [
4]. Bacterial adhesion to stomach epithelial cells leads to the generation of nitrogen and reactive oxygen species (ROS), triggering inflammation and promoting carcinogenesis development [
5].
Studies have demonstrated that nutrition can alter the growth or change of the gastrointestinal microbiome, which can influence chronic disease [
6]. Dietary fatty acids are essential nutrients that impact a variety of disorders throughout life. Polyunsaturated fatty acids (PUFAs) are found in cell membranes and can regulate inflammatory processes and antioxidant signaling pathways [
7]. Omega-3 PUFAs, such as docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and α-linolenic acid (ALA), are known for their antioxidant, anti-inflammatory, and anticancer properties, whereas omega-6 PUFAs, like linoleic acid (LA) and arachidonic acid (AA), are associated with inflammation [
8]. An optimal ratio of omega-6/omega-3 (less than 4 to 1) is necessary for effective regulation and response to external agents, as well as management of inflammation in the body [
7,
9]. However, the Western dietary pattern has a high ratio of omega-6 to 3 PUFAs, which has been associated with an increased risk of inflammation-related disorders [
7].
H. pylori alters the metabolism of omega-6 PUFAs in the gastric mucosal cells of rats, resulting in elevated AA compounds and prostaglandin E2 concentrations [
10]. Omega-3 PUFAs, on the other hand, demonstrate anti-
H. pylori effects. An in vivo study indicated that DHA prevents bacterial colonization and growth in the gastric mucosa of mice by disrupting the bacterial cell membrane [
11]. Furthermore, research on rats found that omega-3 PUFAs reduce gastritis by lowering inflammatory variables such as nitric oxide, malondialdehyde, and gastrin and regulating mucosal glutathione levels [
12]. Moreover, A review study proposed that walnut consumption, as a dietary source of omega-3 PUFAs, might contribute to
H. pylori eradication via regulating inflammation-associated cytokine [
13]. However, Despite the clinical improvement, a trial study found that fish oil supplementation, in combination with pantoprazole and clarithromycin, was ineffective in eliminating
H. pylori [
14].
While the positive effects of omega-3 PUFAs are widely acknowledged, their precise role in
H. pylori infection remains incompletely understood. This current study hypothesized that diets with a low ratio of omega-6 to 3 PUFAs might influence the likelihood of
H. pylori infection due to the anti-inflammatory signaling cascade and ROS purification effects of omega-3 [
13]. To our knowledge, this study is the first to examine the connection between the dietary ratio of omega-6 to omega-3 PUFAs and the probability of
H. pylori infection.
MATERIALS AND METHODS
Study design and participants
The present case-control study was conducted on patients aged 18 to 65 with
H. pylori infection referred to the gastroenterology clinic of Rasoul Akram Hospital, Tehran, Iran from June to November 2021. Participants in the case group were selected from patients who were in the active stage of infection and had not been treated before participating in this study. In the control group, people were selected who were confirmed not to be infected with
H. pylori through diagnostic methods. Those who had previously been diagnosed with
H. pylori and were resistant to treatment or had been treated were excluded from the research. Additionally, individuals with a body mass index (BMI) < 18.5 or > 35, those with malignant or inflammatory disease, a medical history of psychosis, or memory disturbances, individuals following a special diet (vegan, ketogenic, fasting, and etc.), pregnant, lactating, and those who were illiterate to fill out the questionnaire were excluded from the study. Furthermore, after analysis, participants who under-or over-estimated their energy intake (< 800 kcal or > 4,200 /day) were excluded [
15]. All methods were carried out in accordance with relevant guidelines and regulations. The current study was evaluated and approved by the Iran University of Medical Sciences Ethics Committee (IR.IUMS.REC 1396.32632). All patients signed an informed consent form to conduct the study and receive their information.
Demographic data and anthropometric indexes
Data regarding participants' sex (male/female), age, alcohol consumption (yes/no), and smoking (yes/no) of the participants were gathered through a face-to-face interview. The physical activity of the participants was evaluated by the International Physical Activity Questionnaire [
16]. Anthropometric indexes were assessed by a trained dietitian. Height and weight were measured with a digital scale (Seca 807) with a precision of 100 g and a stadiometer (Seca 206) with a precision of 0.5 cm, respectively. BMI was then calculated for each patient with formula. Waist circumference was measured using a flexible tape with a precision of 0.5 cm.
Diagnosis tools
H. pylori infection was diagnosed through different methods, including serological antibody testing (immunoglobulin [Ig] G and IgA) in blood samples, stool antigen testing in fecal matter samples, gastric biopsy, endoscopy, and urea breath test (UBT).
Dietary evaluation
The 168-item food frequency questionnaire (FFQ) was utilized as a validated block format for assessing dietary intakes in the preceding year [
17]. Expert interviewers (MKS and ZE) elicited participants' dietary intake by inquiring about the serving size of each food item, whether consumed yearly, monthly, weekly, or daily. To increase the accuracy of estimations, interviewers presented serving size or household measurements of each food item to participants. Subsequently, the daily consumption of each food item was calculated in grams, considering both the frequency of consumption and the serving size of each food item. Based on the nutrient contents of foods, participants' daily intake of nutrients (micro- and macro-nutrients) was obtained. The gram of omega-3 and omega-6 fatty acids were obtained from food analysis. The omega-3 group includes ALA, EPA, and DHA. The omega-6 group includes LA and AA. Their ratio was then calculated by dividing the values of omega-6 and omega-3.
Qualitative and quantitative variables are presented as frequency (percentage) and mean ± standard deviation, respectively. The comparison of categorical and quantitative variables between two groups was conducted using the chi-square and independent samples t test, respectively. Data normality was evaluated using the Kolmogorov-Smirnov test and histogram chart. Binary logistic regression analysis was utilized to assess the odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for covariates in various models. Additionally, statistical analysis was performed using SPSS software (version 21; SPSS Inc., Chicago, IL, USA). A p value < 0.05 was considered statistically significant.
RESULTS
Among the 500 participants, 150 individuals with confirmed H. pylori infection were categorized as the case group. Meanwhile, 302 volunteers were designated as the control group to evaluate the impact of dietary omega-6 to omega-3 ratios on the likelihood of H. pylori occurrence. This analysis excluded participants who provided inaccurate estimates of their energy intake. Women comprised 59.5% of the participants with a mean age of 39.5 years, and a mean BMI of 26.5 kg/m2. Compared to controls, participants with H. pylori infection smoked significantly more, had a higher BMI, and were older; however, most participants were non-smokers and non-alcohol users. Additionally, there was no significant difference in physical activity between the two groups, with approximately 74% of participants reporting low physical activity levels. Regarding diagnosis methods, 27.8%, 24.5%, 25.8%, and 21.6% of endoscopic biopsy, UBT, serum Ig, and stool antigen were used, respectively.
Patient characteristics are shown in
Table 1. It reveals significant differences in energy, protein, carbohydrate, and monounsaturated fatty acid intake (p < 0.001).
Table 1 The features of case and control participants
Table 1
|
Variables |
Cases (n = 150) |
Controls (n = 302) |
p value |
|
Sex*
|
|
|
0.011
|
|
Male |
48 (32.0) |
135 (44.7) |
|
Female |
102 (68.0) |
167 (55.3) |
|
Helicobacter pylori diagnosis*
|
|
|
0.167 |
|
Endoscopic biopsy |
51 (34.0) |
75 (24.8) |
|
Urea breath test |
30 (20.0) |
81 (26.8) |
|
Serum immunoglobulin |
37 (24.7) |
80 (26.5) |
|
Stool antibody |
32 (21.3) |
66 (21.9) |
|
Smoke status*
|
|
|
0.025
|
|
Yes |
11 (7.3) |
8 (2.6) |
|
No |
139 (92.7) |
294 (97.4) |
|
Alcohol status*
|
|
|
0.203 |
|
Yes |
16 (10.7) |
21 (7.0) |
|
No |
134 (89.3) |
281 (93.0) |
|
Physical activity*
|
|
|
0.484 |
|
Low |
114 (76.0) |
220 (72.8) |
|
Moderate |
29 (19.3) |
59 (19.5) |
|
High |
7 (4.7) |
23 (7.6) |
|
Age (yr)†
|
42.0 ± 13.5 |
37.1 ± 8.4 |
< 0.001
|
|
BMI (kg/m2)†
|
28.1 ± 6.6 |
24.8 ± 3.2 |
< 0.001
|
|
Waist circumference (cm)†
|
108.8 ± 13.6 |
96.5 ± 6.3 |
< 0.001
|
|
Energy (kcal/day)‡
|
2,590.7 (932.8) |
2,246.9 (854.9) |
< 0.001
|
|
Protein (g/day)‡
|
91.6 (39.4) |
72.5 (29.1) |
< 0.001
|
|
Carbohydrate (g/day)‡
|
380.1 (149.0) |
317.3 (129.6) |
< 0.001
|
|
Total fat (g/day)‡
|
76.9 (42.7) |
75.4 (36.9) |
0.429 |
|
SFA (g/day)‡
|
23.4 (11.3) |
25.6 (14.1) |
0.778 |
|
MUFA (g/day)‡
|
24.7 (13.8) |
25.6 (14.6) |
0.004
|
|
PUFA (g/day)‡
|
16.7 (9.4) |
15.5 (9.8) |
0.652 |
Table 2 shows the food group intake based on energy distribution. Significant differences were observed in legumes, starchy vegetables, green leafy vegetables, dairy products, chickens, red meats, nuts (p < 0.001, for all), fruits (p = 0.030), whole grains (p = 0.007), vegetable oils (p = 0.002), organ meats (p = 0.035), fishes (p = 0.019), and added sugars (p = 0.010) between the case and control groups.
Table 2 Food group intake between the case and control participants (% of total energy)
Table 2
|
Variables |
Cases (n = 150) |
Controls (n = 302) |
p value |
|
Refined grains |
28.4 ± 12.8 |
27.7 ± 12.2 |
0.578 |
|
Whole grains |
17.4 ± 13.5 |
13.9 ± 12.3 |
0.007
|
|
Nuts |
3.5 ± 3.3 |
2.0 ± 2.6 |
< 0.001
|
|
Legumes |
3.4 ± 2.7 |
1.3 ± 1.8 |
< 0.001
|
|
Fruits |
8.8 ± 4.6 |
10.1 ± 6.7 |
0.030
|
|
Green leafy vegetables |
1.0 ± 0.8 |
0.7 ± 0.5 |
< 0.001
|
|
Yellowy vegetables |
0.2 ± 0.3 |
0.3 ± 0.3 |
0.468 |
|
Starchy vegetables |
0.8 ± 0.7 |
1.4 ± 1.2 |
< 0.001
|
|
Other vegetables |
3.6 ± 1.8 |
3.5 ± 1.4 |
0.556 |
|
Vegetable oils |
5.8 ± 4.5 |
4.4 ± 4.1 |
0.002
|
|
Animal fats |
2.1 ± 3.3 |
2.2 ± 2.7 |
0.826 |
|
Red meats |
0.9 ± 0.8 |
2.7 ± 2.6 |
< 0.001
|
|
Organ meats |
0.1 ± 0.2 |
0.1 ± 0.2 |
0.035
|
|
Processed meats |
0.4 ± 0.7 |
0.5 ± 0.8 |
0.154 |
|
Chickens |
3.8 ± 3.1 |
2.6 ± 2.6 |
< 0.001
|
|
Eggs |
1.3 ± 1.1 |
1.2 ± 1.1 |
0.298 |
|
Fishes |
0.6 ± 0.6 |
0.8 ± 0.7 |
0.019
|
|
Dairy products |
10.9 ± 5.3 |
16.9 ± 7.5 |
< 0.001
|
|
Sweetened beverages |
1.0 ± 1.2 |
0.8 ± 1.1 |
0.160 |
|
Added sugars |
5.5 ± 3.5 |
6.4 ± 4.0 |
0.010
|
The crude and multivariable-adjusted OR and 95% CI for
H. pylori across tertiles of omega-6 to omega-3 ratio are displayed in
Table 3. In the crude model, participants in the last tertile were significantly more likely to be infected with
H. pylori than those in the first tertile (OR, 2.10; 95% CI, 1.30–3.40). Furthermore, the association remained significant even after adjusting for potential confounders in models 2 and 3 (model 2: OR, 2.12; 95% CI, 1.26–3.55 and model 3: OR, 2.00; 95% CI, 1.17–3.34).
Table 3 Association between tertiles of omega-6/omega-3 ratio and Helicobacter pylori infection
Table 3
|
Tertiles of omega 6 to 3 ratio |
Case/control, No. |
Model 1*
|
Model 2†
|
Model 3‡
|
|
Omega 6 to 3 ratio |
|
|
|
|
|
T1 (≤ 10.10) |
42/108 |
1.00 (Ref.) |
1.00 (Ref.) |
1.00 (Ref.) |
|
T2 (10.11–10.82) |
40/111 |
0.92 (0.55–1.53) |
1.02 (0.59–1.75) |
1.04 (0.59–1.82) |
|
T3 (≥ 10.83) |
68/83 |
2.10 (1.30–3.40)
|
2.12 (1.26–3.55)
|
2.00 (1.17–3.41)
|
|
ptrend
|
|
0.002
|
0.004
|
0.011
|
DISCUSSION
The current case-control study revealed that higher omega-6 to 3 ratios were associated with a 2-fold odds of H. pylori infection. Additionally, the findings indicated an increase in developing H. pylori with increasing age and BMI.
H. pylori is a significant factor in stomach and duodenal ulcers, chronic active gastritis, and gastric cancer [
3]. While most people with
H. pylori do not show clinical symptoms, the infection causes inflammation of the stomach epithelium, with approximately1%–3% of individuals getting stomach cancer and 10% suffering from peptic ulcers [
18]. Eradicating
H. pylori bacteria is a severe problem due to the presence of treatment-resistant strains, making the discovery of novel medications or solutions critical in determining the rate of eradication [
19]. Many dietary components can have considerable antibacterial activity against
H. pylori. Dietary changes can limit the colonization process of this bacterium, and thus the occurrence of gastritis [
20].
Inflammatory substances secreted by
H. pylori are advantageous to the bacteria but detrimental to the host. The inflammation disrupts the secretory function of the stomach and damages its tissue [
21]. Dietary components, notably PUFAs, have the ability to regulate antioxidant signaling pathways and modulate inflammatory processes [
22]. Clinical research indicates a positive association between the occurrence of bacterial infections and inflammation [
23]. It has been proposed that consuming omega-3 fatty acids, such as DHA and EPA, within the range of 3 to 5 g, may reduce the risk of chronic diseases, particularly cardiovascular diseases, and exhibit anti-inflammatory properties [
22,
24]. Furthermore, omega-3 PUFAs appear to protect the stomach from gastric mucosa damage caused by stress, medications, and
H. pylori infection [
25]. Additionally, omega-3 PUFAs can reduce stomach inflammation produced by
H. pylori by reducing the expression of interleukin (IL)-8, which has pro-inflammatory features [
26]. Yamamoto et al. [
27] showed that omega-3 fatty acids (100 μM of EPA and DHA each) effectively block
H. pylori infection in mouse stomachs by inhibiting bacterial colonization through futalosine pathway blockade, with EPA showing greater efficacy than DHA.
Regions with high EPA + DHA blood levels (> 8%) were the Sea of Japan, Scandinavia, and areas with indigenous populations or populations not fully adapted to Westernized food habits. Conversely, very low blood levels (≤ 4%) were observed in North America, Central and South America, Europe, the Middle East, Southeast Asia, and Africa [
28]. Several research have investigated the impact of dietary or supplemental PUFAs (including both omega-3 and omega-6 PUFAs, or omega-3 fatty acids alone) on the growth and elimination of
H. pylori. In a double-blind, randomized clinical trial (RCT), Meier et al. [
14] found that in patients with dyspepsia without an ulcer, adding fish oil (1,500 mg/3 times/day for one week) was less effective than metronidazole in the treatment of
H. pylori when combined with pantoprazole and clarithromycin. Their study showed that omega-3 consumption could not eradicate
H. pylori [
14]. Similarly, there was no significant difference in the rates of eradication in a double-blind RCT with 97
H. pylori patients who took 2 g of EPA and DHA every day for 12 weeks along with four common
H. pylori-eradication drugs. However, there was a statistically significant decrease in IL-8 and high sensitivity C-reactive protein levels [
29].
It is evident that DHA and EPA inhibit bacterial growth [
30]. Moreover, according to reports, omega-3 fatty acid consumption has been associated with antibacterial effects at concentrations exceeding 500 mg per day [
31]. Furthermore, Thompson et al. [
32] demonstrated that the growth of
H. pylori was moderately inhibited by the addition of PUFAs, including omega-6 and omega-3. Additionally, Correia et al. [
11] found that DHA altered the shape of
H. pylori bacteria, inhibiting their development and colonization in mice's stomachs.
Omega-3 fatty acid antimicrobial mechanisms may include interruption of adenosine triphosphate generation, cell-to-cell communication, the electron transport system, fatty acid synthesis, alterations in membrane hydrophobicity, and cellular leakage [
33]. In line with these findings, our study confirmed that higher dietary omega-3 consumption might protect against
H. pylori overgrowth.
In addition, it has been discovered that omega-3 fatty acids exhibit antioxidant properties [
7,
34], which directly correlates with their antimicrobial effect [
35]. Further studies have shown that antioxidant compounds suppress microbial growth through various mechanisms, including the leakage of intracellular proteins, modification of essential fatty acids in organisms, and binding to electron donors inside the cell [
36].
LA, an essential omega-6 fatty acid in the human diet, is converted by the body into other omega-6 PUFAs such as dihomo-gamma-linolenic acid, gamma-linolenic acid, and AA [
37]. One of the important PUFAs found in the cell membrane is AA, which leads to inflammation by producing eicosanoids [
38]. It has been demonstrated that a lower in the omega-6 to omega-3 fatty acid ratio is associated with reduced inflammation. Conversely, an increase in the ratio of omega-6 to omega-3 PUFAs has been linked to increased pro-inflammatory cytokines and eicosanoids [
39]. Therefore, not only is consuming of omega-3 fatty acids important for reducing inflammation, but also maintaining a balanced omega-6 to omega-3 ratio (lower than 4 to 1), is recommended [
40]. In addition, an increase in the ratio of omega-6 to omega-3 PUFAs is related to reduced immune system function [
41]. Consequently, the high ratio of omega-6 to omega-3 PUFAs provides a susceptible environment for the growth of
H. pylori by causing inflammation and changing the function of the immune system. In the present study, the findings indicated if the omega-6 to omega-3 ratio is more than 10.83, the chance of developing
H. pylori is higher. This relationship remained positive and significant after adjusting for confounding factors.
Furthermore, Wang et al. [
42] found that some alterations in gut microbial species and functions are associated with
H. pylori infection. Additionally, a study by Ghosh et al. [
43] illustrated that omega-6 causes dysbiosis, while omega-3 can eliminate this effect. Therefore, increasing the omega-6 to omega-3 ratio may increase the chance of developing
H. pylori infection.
The present study’s findings also showed that in individuals infected with
H. pylori, BMI is significantly higher than in the control group. Xu et al. [
44] similarly showed a positive association between BMI and
H. pylori infection. In addition, it was shown in research by Satoh et al. [
45] that
H. pylori was higher in obese people than in the control group. Obesity is recognized to be associated with an increased risk of infection by various pathogens [
46]. Moreover, an increased degree of obesity is also linked to impaired immune function [
47]. Therefore, the increase in the chance of developing
H. pylori with an increase in BMI can be justified by the abovementioned reasons.
The present study has several strengths. To the best of our knowledge, this study represents the first attempt to assess the association between ratio of omega-6 to omega-3 PUFAs and odds of H. pylori infection. Moreover, it included the use of valid and reliable questionnaires, face-to-face interviews for data collection, and the full participation of almost all identified people in the control and case groups.
However, there are several limitations in our study. Firstly, misclassification and recall bias may occur when using FFQ for dietary assessment, especially among patients infected by H. pylori who have altered their lifestyle due to symptoms. Secondly, there was a lack of details regarding cooking methods, which may alter the configuration of PUFAs through high heating. Lastly, as a general concern with case-control studies, causal relationships cannot be inferred from these types of studies.
CONCLUSION
The study showed that a higher intake ratio of omega-6 to omega-3 PUFAs was linked to an increased risk of H. pylori infection, suggesting that dietary changes could be beneficial in preventing and managing this condition. However, more research is required to validate these findings and explore how omega-3 and omega-6 fatty acids impact H. pylori survival, potentially deepening our comprehension of these connections.
NOTES
-
Conflict of Interest: The authors declare that they have no competing interests.
-
Author Contributions:
Conceptualization: Ebrahimi Z, Sikaroudi MK, Masoodi M, Shidfar F.
Data curation: Sikaroudi MK, Ebrahimi Z, Masoodi M.
Formal analysis: Sikaroudi MK, Nouri M.
Investigation: Sikaroudi MK, Nouri M.
Writing - original draft: Darzi M, Sikaroudi MK, Shateri Z, Nouri M, Masoodi M, Shidfar F.
Writing - review & editing: Darzi M, Sikaroudi MK, Masoodi M, Hejazi M, Shidfar F.
ACKNOWLEDGEMENTS
We thank the patients who graciously agreed to participate in this research and the staff who contributed to this study.
REFERENCES
- 1. Morgan E, Arnold M, Camargo MC, Gini A, Kunzmann AT, et al. The current and future incidence and mortality of gastric cancer in 185 countries, 2020–40: a population-based modelling study. EClinicalMedicine 2022;47:101404.
- 2. Plummer M, de Martel C, Vignat J, Ferlay J, Bray F, et al. Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Health 2016;4:e609-e616.
- 3. Bardazzi F, Magnano M, Fiorini G, Vaira D, Odorici G, et al. Helicobacter pylori infection in psoriatic patients during biological therapy. Ital J Dermatol Venerol 2021;156:570-574.
- 4. Mezmale L, Coelho LG, Bordin D, Leja M. Review: epidemiology of Helicobacter pylori. Helicobacter 2020;25(Suppl 1):e12734.
- 5. Conteduca V, Sansonno D, Lauletta G, Russi S, Ingravallo G, et al. H. pylori infection and gastric cancer: state of the art (review). Int J Oncol 2013;42:5-18.
- 6. Horn J, Mayer DE, Chen S, Mayer EA. Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders. Transl Psychiatry 2022;12:164.
- 7. Djuricic I, Calder PC. Beneficial outcomes of omega-6 and omega-3 polyunsaturated fatty acids on human health: an update for 2021. Nutrients 2021;13:2421.
- 8. Burlingame B, Nishida C, Uauy R, Weisell R. Fats and fatty acids in human nutrition: introduction. Ann Nutr Metab 2009;55:5-7.
- 9. Simopoulos AP. An increase in the omega-6/omega-3 fatty acid ratio increases the risk for obesity. Nutrients 2016;8:128.
- 10. Nakaya A, Wakabayashi H, Imamura L, Fukuta K, Makimoto S, et al. Helicobacter pylori alters n-6 fatty acid metabolism and prostaglandin E2 synthesis in rat gastric mucosal cells. J Gastroenterol Hepatol 2001;16:1197-1205.
- 11. Correia M, Michel V, Matos AA, Carvalho P, Oliveira MJ, et al. Docosahexaenoic acid inhibits Helicobacter pylori growth in vitro and mice gastric mucosa colonization. PLoS One 2012;7:e35072.
- 12. Mohammed A, Janakiram NB, Brewer M, Duff A, Lightfoot S, et al. Endogenous n-3 polyunsaturated fatty acids delay progression of pancreatic ductal adenocarcinoma in Fat-1-p48(Cre/+)-LSL-Kras(G12D/+) mice. Neoplasia 2012;14:1249-1259.
- 13. Park JM, Jeong M, Kim EH, Han YM, Kwon SH, et al. Omega-3 polyunsaturated fatty acids intake to regulate Helicobacter pylori-associated gastric diseases as nonantimicrobial dietary approach. BioMed Res Int 2015;2015:712363.
- 14. Meier R, Wettstein A, Drewe J, Geiser HR. Swiss Helicobacter-Study Group. Fish oil (Eicosapen) is less effective than metronidazole, in combination with pantoprazole and clarithromycin, for Helicobacter pylori eradication. Aliment Pharmacol Ther 2001;15:851-855.
- 15. Fung TT, Hu FB, Pereira MA, Liu S, Stampfer MJ, et al. Whole-grain intake and the risk of type 2 diabetes: a prospective study in men. Am J Clin Nutr 2002;76:535-540.
- 16. Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 2003;35:1381-1395.
- 17. Esfahani FH, Asghari G, Mirmiran P, Azizi F. Reproducibility and relative validity of food group intake in a food frequency questionnaire developed for the Tehran Lipid and Glucose Study. J Epidemiol 2010;20:150-158.
- 18. Peek RM Jr, Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer 2002;2:28-37.
- 19. Ikezaki H, Furusyo N, Jacques PF, Shimizu M, Murata M, et al. Higher dietary cholesterol and ω-3 fatty acid intakes are associated with a lower success rate of Helicobacter pylori eradication therapy in Japan. Am J Clin Nutr 2017;106:581-588.
- 20. Hołubiuk Ł, Imiela J. Diet and Helicobacter pylori infection. Prz Gastroenterol 2016;11:150-154.
- 21. Blaser MJ. Hypotheses on the pathogenesis and natural history of Helicobacter pylori-induced inflammation. Gastroenterology 1992;102:720-727.
- 22. Marion-Letellier R, Savoye G, Ghosh S. Polyunsaturated fatty acids and inflammation. IUBMB Life 2015;67:659-667.
- 23. Meduri GU. Clinical review: a paradigm shift: the bidirectional effect of inflammation on bacterial growth. Clinical implications for patients with acute respiratory distress syndrome. Crit Care 2002;6:24-29.
- 24. Weylandt KH, Chen YQ, Lim K, Su HM, Cittadini A, et al. ω -3 PUFAs in the prevention and cure of inflammatory, degenerative, and neoplastic diseases 2014. BioMed Res Int 2015;2015:695875.
- 25. Manjari V, Das UN. Effect of polyunsaturated fatty acids on dexamethasone-induced gastric mucosal damage. Prostaglandins Leukot Essent Fatty Acids 2000;62:85-96.
- 26. Lee SE, Lim JW, Kim JM, Kim H. Anti-inflammatory mechanism of polyunsaturated fatty acids in Helicobacter pylori-infected gastric epithelial cells. Mediators Inflamm 2014;2014:128919.
- 27. Yamamoto T, Matsui H, Yamaji K, Takahashi T, Øverby A, et al. Narrow-spectrum inhibitors targeting an alternative menaquinone biosynthetic pathway of Helicobacter pylori. J Infect Chemother 2016;22:587-592.
- 28. Stark KD, Van Elswyk ME, Higgins MR, Weatherford CA, Salem N Jr. Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults. Prog Lipid Res 2016;63:132-152.
- 29. Khandouzi N, Shidfar F, Agah S, Hosseini AF, Dehnad A. Comparison of the effects of eicosapentaenoic acid and docosahexaenoic acid on the eradication of Helicobacter pylori infection, serum inflammatory factors and total antioxidant capacity. Iran J Pharm Res 2015;14:149-157.
- 30. Cheng CL, Huang SJ, Wu CL, Gong HY, Ken CF, et al. Transgenic expression of omega-3 PUFA synthesis genes improves zebrafish survival during Vibrio vulnificus infection. J Biomed Sci 2015;22:103.
- 31. Husson MO, Ley D, Portal C, Gottrand M, Hueso T, et al. Modulation of host defence against bacterial and viral infections by omega-3 polyunsaturated fatty acids. J Infect 2016;73:523-535.
- 32. Thompson L, Cockayne A, Spiller RC. Inhibitory effect of polyunsaturated fatty acids on the growth of Helicobacter pylori: a possible explanation of the effect of diet on peptic ulceration. Gut 1994;35:1557-1561.
- 33. Chanda W, Joseph TP, Guo XF, Wang WD, Liu M, et al. Effectiveness of omega-3 polyunsaturated fatty acids against microbial pathogens. J Zhejiang Univ Sci B 2018;19:253-262.
- 34. Heshmati J, Morvaridzadeh M, Maroufizadeh S, Akbari A, Yavari M, et al. Omega-3 fatty acids supplementation and oxidative stress parameters: a systematic review and meta-analysis of clinical trials. Pharmacol Res 2019;149:104462.
- 35. Albonetti S, Minardi P, Trombetti F, Savigni F, Mordenti AL, et al. In vivo and in vitro effects of selected antioxidants on rabbit meat microbiota. Meat Sci 2017;123:88-96.
- 36. Fung DY, Lin CC, Gailani MB. Effect of phenolic antioxidants on microbial growth. Crit Rev Microbiol 1985;12:153-183.
- 37. Innes JK, Calder PC. Omega-6 fatty acids and inflammation. Prostaglandins Leukot Essent Fatty Acids 2018;132:41-48.
- 38. Calder PC. Eicosanoids. Essays Biochem 2020;64:423-441.
- 39. DiNicolantonio JJ, O’Keefe JH. Importance of maintaining a low omega-6/omega-3 ratio for reducing inflammation. Open Heart 2018;5:e000946.
- 40. Sut A, Chiżyński K, Różalski M, Golański J. Dietary intake of omega fatty acids and polyphenols and its relationship with the levels of inflammatory markers in men with chronic coronary syndrome after percutaneous coronary intervention. Kardiol Pol 2020;78:117-123.
- 41. Kew S, Banerjee T, Minihane AM, Finnegan YE, Williams CM, et al. Relation between the fatty acid composition of peripheral blood mononuclear cells and measures of immune cell function in healthy, free-living subjects aged 25–72 y. Am J Clin Nutr 2003;77:1278-1286.
- 42. Wang D, Li Y, Zhong H, Ding Q, Lin Y, et al. Alterations in the human gut microbiome associated with Helicobacter pylori infection. FEBS Open Bio 2019;9:1552-1560.
- 43. Ghosh S, DeCoffe D, Brown K, Rajendiran E, Estaki M, et al. Fish oil attenuates omega-6 polyunsaturated fatty acid-induced dysbiosis and infectious colitis but impairs LPS dephosphorylation activity causing sepsis. PLoS One 2013;8:e55468.
- 44. Xu C, Yan M, Sun Y, Joo J, Wan X, et al. Prevalence of Helicobacter pylori infection and its relation with body mass index in a Chinese population. Helicobacter 2014;19:437-442.
- 45. Satoh H, Saijo Y, Yoshioka E, Tsutsui H. Helicobacter pylori infection is a significant risk for modified lipid profile in Japanese male subjects. J Atheroscler Thromb 2010;17:1041-1048.
- 46. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature 2006;444:1022-1023.
- 47. Andersen CJ, Murphy KE, Fernandez ML. Impact of obesity and metabolic syndrome on immunity. Adv Nutr 2016;7:66-75.
, Zohreh Ebrahimi3
