Dairy Consumption and Inflammatory Bowel Disease among Arab Adults: A Case–Control Study and Meta-Analysis

Background: Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is a complex disease with increasing global incidence and prevalence. Although dairy consumption has been linked to various chronic diseases, its relationship with IBD remains uncertain. Additionally, there is a lack of data on this topic from Arab countries. This study aimed to investigate the association between dairy consumption and IBD through a case–control study among Arab populations, followed by a meta-analysis of available studies. Method: First, we used data from 158 UC patients, 244 CD patients, and 395 controls attending a polyclinic in Riyadh, Saudi Arabia. All participants were aged ≥ 18 years. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) of UC and CD for individuals who reported the highest versus the lowest frequencies of dairy consumption. Next, we conducted a meta-analysis, combining our results with those from other eligible studies after searching several databases. We used the I2 statistics to examine statistical heterogeneity across studies and the regression test for funnel plot asymmetry to assess publication bias. Results: The case–control study showed a negative association between frequent dairy consumption and UC (OR (95% CI) = 0.64 (0.41, 1.00)) but not CD (OR (95% CI) = 0.97 (0.65, 1.45)). In the meta-analysis, the highest frequencies of dairy consumption were negatively associated with both UC and CD: ORs (95% CIs) = 0.82 (0.68, 0.98) and 0.72 (0.59, 0.87), respectively. A moderate heterogeneity across studies was noticed in the UC meta-analysis (I2 = 59.58%) and the CD meta-analysis (I2 = 41.16%). No publication bias was detected. Conclusions: Frequent dairy consumption could protect against the development of UC and CD, suggesting potential dietary recommendations in the context of IBD prevention.


Introduction
Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), represents a group of chronic inflammatory conditions that affect the gastroin-testinal tract [1].These diseases are characterized by periods of active inflammation and remission, causing symptoms such as abdominal pain, diarrhea, rectal bleeding, weight loss, and fatigue [1].The incidence and prevalence of IBD have been steadily rising globally, making it a significant public health challenge.This increase is observed not only in Western countries, where IBD has traditionally been more common, but also in newly industrialized and developing nations, suggesting a possible link to changing environmental and lifestyle factors [2,3].
The etiology of IBD is complex and multifactorial, involving a combination of genetic, environmental, and immunological factors.Genetic predisposition plays a crucial role, with numerous susceptibility genes identified that contribute to the disease's development.Environmental factors, such as smoking, antibiotic use, and urbanization, have also been implicated.Among these, diet is considered a particularly influential environmental component.Specific dietary components, such as high-fat and high-sugar foods, have been associated with an increased risk of IBD, while dietary fiber and certain micronutrients may offer protective effects [4][5][6][7].
Among various dietary factors, dairy products, such as milk, cheese, and yogurt, a staple in many diets worldwide, have garnered significant attention.The biological mechanisms through which dairy consumption might influence IBD are multifaceted.On the one hand, lactose intolerance can exacerbate gastrointestinal symptoms, potentially triggering inflammatory processes in predisposed individuals [8].Proteins in dairy, like casein and whey, may provoke immune responses and contribute to gut inflammation.Dairy consumption can also impact the gut microbiome, disrupting the balance of bacterial species and influencing inflammation.Additionally, saturated fats in dairy may alter gut barrier function and permeability, leading to increased bacterial translocation and further inflammation [9,10].On the other hand, dairy products contain bioactive peptides that modulate immune responses and inhibit inflammation.They are also rich in calcium and vitamin D, which are beneficial for gut health.Calcium helps maintain gut barrier integrity, while vitamin D supports immune function and has anti-inflammatory effects.Probiotics in fermented dairy products can promote a healthy gut microbiome.These factors contribute to the potential protective effects of dairy against the development of IBD [9].
Evidence on the association between dairy consumption and IBD remains inconclusive due to conflicting results of epidemiological studies .While some studies indicated that dairy consumption could offer a protective effect against IBD [11,12,18], other studies showed no association between dairy consumption and IBD [14,19] or even increased IBD risk alongside the increasing dairy consumption [27].Additionally, some studies did not include a sufficient number of cases to achieve a statistically significant association [16,22].In addition, most of these studies were conducted on Western and East Asian populations, limiting their generalizability to other populations.
In Arab countries, dairy consumption is a significant cultural practice.Dairy product sales in the Gulf Cooperation Council countries increased by 50% between 2007 and 2012, with the Saudi market accounting for 74% of this volume.Saudi consumers also demonstrated the highest per capita dairy consumption [41].Still, the role of dairy consumption in the development of IBD among Arab populations remains understudied.
Given the absence of data on the association between dairy consumption and IBD in Arab populations, we conducted a case-control study at a Saudi polyclinic to examine this association.Due to inconsistent findings across previous studies and the insufficient number of IBD cases in some research, we also performed a systematic review of the literature on the relationship between dairy consumption and the risk of IBD.By combining our study results with those from previous studies in a meta-analysis, we aimed to draw more definitive conclusions about the role of dairy consumption in the development of UC and CD.

Study Design, Population, and Setting
Sample size calculation was conducted using Epi Info based on the following: twosided confidence level (1-alpha): 95; power (% chance of detecting): 80; the ratio of controls to cases: 2; hypothetical proportion of controls with exposure: 50; hypothetical proportion of cases with exposure: 30; and the least extreme odds ratio (OR) to be detected: 0.43.The calculated sample size was 73 for cases and 146 for controls, given that UC and CD were investigated separately.We more than doubled the sample size to account for the potential lack of data on dairy consumption and to enable stratified results by sex.For this hospitalbased case-control study, data from 171 participants with UC, 251 participants with CD, and 400 participants with other gastrointestinal conditions (who served as controls) were obtained.All participants were diagnosed in a private polyclinic in Riyadh between January 2009 and December 2017.To be included in the IBD group, participants had to be newly diagnosed with IBD.To be included in the control group, participants had to show no signs of IBD, drug colitis, malignancy, polyposis, or diverticulosis [42,43].Participants with no data on dairy consumption were excluded, leaving 158 participants with UC, 244 participants with CD, and 395 controls for statistical analysis.All participants were aged ≥18 years.

Assessment of Inflammatory Bowel Disease
As described elsewhere [42,43], participants with IBD manifestations, such as abdominal pain, diarrhea, bloating, loss of appetite, unexplained weight loss, or bloody stool, were subjected to laboratory investigations, including urine and stool analysis for biomarkers of inflammation and serum complete blood count, C-reactive protein, erythrocyte sedimentation rates, bilirubin, alanine aminotransferase, creatinine, and alkaline phosphatase.Participants with manifestations and laboratory findings suggesting IBD underwent gastrointestinal endoscopies.Histopathological analysis of specimens was conducted to confirm the diagnosis.

Assessment of Dairy Consumption
Data on dairy consumption were collected using a self-administered questionnaire distributed before diagnoses were made.The following question was used to assess dairy consumption in a typical week: "How frequently do you consume dairy products?"The available responses were "once per month or less", "once per week", "twice per week", "every day", "do not remember", and "NA."We merged the responses "once per month or less", "once per week", and "twice per week" into one category, "infrequent consumption", to obtain statistical power, while the response "every day" was categorized as "frequent consumption."Participants with the responses "do not remember" and "NA" were excluded from the analysis.Illiterate participants sought help from the data collectors.Dairy products included milk, yogurt, and cheese.Food frequency questions were not validated or pre-tested.

Statistical Analysis
Logistic regression was used to compute the ORs and 95% confidence intervals (CIs) for IBD, UC, and CD in the case of frequent versus infrequent dairy consumption.The results were adjusted for age, sex, and body mass index (BMI).The results were further stratified by sex.The Statistical Package for Social Science (SPSS) 2013 (IBM SPSS Statistics for Windows, version 22.0, IBM Corporation, Armonk, NY, USA) was used for data analysis.

Literature Review and Eligibility Criteria
We performed the meta-analysis per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [44].Two authors independently conducted thorough searches of the Medline (PubMed), Web of Science, and Scopus databases to locate relevant studies published up to 10 June 2024 (Supplementary Table S1).In addition, we manually reviewed the reference lists of the identified studies and related review articles to find any further relevant studies.There were no restrictions on the publication year.

Eligibility Criteria
Studies were included in this meta-analysis if (1) the consumption of dairy or any of its subtypes was the exposure, (2) the outcome was IBD, UC, or CD, (3) participants were adults, and (4) the risk estimate or prevalence of IBD, UC, or CD associated with dairy consumption was provided.

Study Selection
Two authors independently reviewed the titles and abstracts of all studies retrieved from the initial search.These studies were then assessed against the established eligibility criteria to compile the final list for the meta-analysis.

Data Extraction
Two authors independently extracted the following data from the included studies: the last name of the first author, the year of publication, the study location, the sample size, the study design, the types of IBD, the categories of dairy consumption, adjusted variables, and risk estimates.When a given study provided different regression models that adjusted for several variables, we included the model that adjusted for the largest number of variables.

Risk of Bias and Quality Assessment
The quality of the individual studies was evaluated using the modified Newcastle-Ottawa Scale (NOS).Cross-sectional and case-control studies were evaluated based on definitions and representativeness of cases and controls, comparability, and ascertainment of dairy consumption (applying the same method of dairy consumption ascertainment for cases and controls), and nonresponse rate.Cohort studies were evaluated based on the representativeness of the exposed cohort, ascertainment of dairy consumption, selection of the non-exposed cohort (excluding IBD cases at baseline), comparability, IBD assessment, and length of follow-up of outcome [45].Two authors independently conducted these assessments, resolving any disagreements through discussion and consultation with the other authors.

Statistical Analysis
The random effects model was applied to compute the pooled odds ratio (OR) and 95% confidence interval (95% CI) for IBD, UC, and CD among participants who reported the highest versus the lowest frequencies of dairy consumption [46].We calculated tau 2 (estimated amount of total heterogeneity), I 2 (total heterogeneity/total variability), and H 2 (total variability/sampling variability) statistics to examine statistical heterogeneity across studies [47].Publication bias was assessed using the regression test for funnel plot asymmetry [48].We conducted sensitivity analyses by removing studies one by one and combining the remaining studies.The R 3.2.0statistical package (Metafor: Meta-Analysis Package for R) was used for statistical analysis [49].

The Meta-Analysis
Most studies were excluded for being duplicates or reviews or having irrelevant exposures (dairy consumption) or outcomes (IBD, UC, or CD).Ultimately, we identified 19 studies that met the criteria for inclusion in this meta-analysis (Figure 1).The studies were published between 1991 and 2024.The risk estimates were calculated for dairy consumption as a whole in 11 studies, milk consumption in 7 studies, and cheese consumption in 1 study.The study designs were distributed as follows: 13 case-control studies, 4 prospective cohort studies, and 2 cross-sectional studies.The outcomes investigated were as follows: 15 studies investigated UC, 9 studies investigated CD, and 6 studies investigated IBD as a whole (Table 3).Among the 15 case-control and cross-sectional studies, 3 studies had good quality (scores 7/9), 10 studies had average quality (scores 5-6/9), and 2 studies had poor quality (scores 3/9).However, all cohort studies had good quality, with a minimum risk of major bias (scores 7-9/9) (Table 4).

The Meta-Analysis
Most studies were excluded for being duplicates or reviews or having irrelevant exposures (dairy consumption) or outcomes (IBD, UC, or CD).Ultimately, we identified 19 studies that met the criteria for inclusion in this meta-analysis (Figure 1).The studies were published between 1991 and 2024.The risk estimates were calculated for dairy consumption as a whole in 11 studies, milk consumption in 7 studies, and cheese consumption in 1 study.The study designs were distributed as follows: 13 case-control studies, 4 prospective cohort studies, and 2 cross-sectional studies.The outcomes investigated were as follows: 15 studies investigated UC, 9 studies investigated CD, and 6 studies investigated IBD as a whole (Table 3).Among the 15 case-control and crosssectional studies, 3 studies had good quality (scores 7/9), 10 studies had average quality (scores 5-6/9), and 2 studies had poor quality (scores 3/9).However, all cohort studies had good quality, with a minimum risk of major bias (scores 7-9/9) (Table 4).The possible overall scores range between 0 and 9. Every * represents 1 point.

Discussion
The case-control study, investigating Saudi participants, indicated a negative association between dairy consumption and UC only, while the meta-analysis showed a negative association between dairy consumption and both UC and CD.This finding challenges some previous notions that dairy, particularly due to its lactose content, might contribute to the development of IBD in susceptible individuals.Instead, this study

Discussion
The case-control study, investigating Saudi participants, indicated a negative association between dairy consumption and UC only, while the meta-analysis showed a negative association between dairy consumption and both UC and CD.This finding challenges some previous notions that dairy, particularly due to its lactose content, might contribute to the development of IBD in susceptible individuals.Instead, this study supports the hypothesis that dairy products might have protective effects or that the avoidance of dairy might be associated with other dietary patterns that increase IBD risk.
The protective effect of dairy consumption against UC and CD is multi-faceted, involving several interrelated mechanisms.Firstly, dairy products provide probiotic benefits, contributing beneficial bacteria to the gut, which can enhance intestinal health and function [50].Secondly, the anti-inflammatory properties of specific dairy components, such as casein and whey proteins, can help reduce inflammation in the gut [51].Additionally, dairy is a rich source of calcium and vitamin D, both of which play crucial roles in maintaining gut integrity and immune function [52,53].Furthermore, the consumption of dairy leads to the production of short-chain fatty acids (SCFAs) through the fermentation of lactose by gut bacteria.SCFAs, such as butyrate, propionate, and acetate, serve as energy sources for colon cells and have anti-inflammatory effects, contributing to overall gut health [54,55].Finally, dairy consumption favorably modulates the composition of the gut microbiota, promoting the growth of beneficial bacterial species that can outcompete harmful pathogens and reduce gut inflammation [56].These diverse mechanisms may work synergistically to maintain gut health and prevent the onset of IBD by reducing inflammation and supporting a balanced gut microbiome.
The finding that dairy consumption is associated with a lower risk of UC and CD has significant clinical implications.Healthcare providers might consider recommending the inclusion of dairy products in the diets of individuals at risk of IBD, provided there are no contraindications, such as lactose intolerance or dairy allergies.Nutritional counseling can emphasize the potential benefits of dairy, including its anti-inflammatory components and essential nutrients, which may promote gut health and modulate immune responses.Preventive strategies could integrate dairy as part of a balanced diet to reduce inflammation and support overall digestive health.Public health policies might incorporate these findings into dietary guidelines, promoting dairy consumption as a preventive measure against IBD, particularly in regions with rising prevalence [57].
Of note, investigating an understudied population, assigning newly diagnosed IBD patients, and using standardized methods for IBD diagnosis are the main strengths of the case-control study.However, it carried several limitations.First, data were collected from patients attending a single polyclinic in Riyadh, the largest urban city in Saudi Arabia.This polyclinic is a private institution, suggesting that our patients might have had a higher socio-economic status.Therefore, caution is needed when generalizing our results to people from rural areas and poorer suburbs.Second, we did not use a validated food frequency questionnaire, which could have affected the accuracy and reliability of dietary intake data.Third, we did not gather information on the various components of dairy, which might have distinct associations with IBD.Dairy consumption was investigated as a whole rather than focusing on specific nutrients, such as vitamin D and calcium, which could have different effects on IBD risk.Fourth, due to the limited number of cases in each dairy consumption frequency group, we combined the groups representing non-daily dairy consumption into one group.As a result, a dose-response association could not be evaluated, limiting our ability to understand how varying levels of dairy intake affect IBD risk.Fifth, while the study used standardized approaches to ascertain IBD diagnosis, IBD activity scores were not calculated.Sixth, the results were not adjusted for several important variables, such as total calorie intake, which could confound the association between dairy consumption and IBD.Seventh, since controls were patients with other gastrointestinal manifestations that could be related to dairy consumption, the association might have been impacted, potentially biasing our findings.Eighth, patients were recruited over a relatively long period, during which popular trends toward dairy consumption might have changed, adding another layer of variability to the data.
Augmenting the number of UC and CD cases by involving a large number of studies was the main strength of the meta-analysis.However, it also had several limitations.First, the included studies varied in design, sample size, and dairy consumption categorization, potentially introducing heterogeneity.Second, the observational nature of these studies prevented the firm establishment of causality.Third, confounding factors, such as overall diet quality, total energy consumption, and lifestyle factors, were not uniformly controlled across studies.Fourth, although the meta-analysis was conducted according to standard procedures, its protocol was not registered in advance.

Conclusions
Dairy consumption was associated with a decreased risk of UC and CD.Our findings hold implications for dietary recommendations in the context of IBD prevention and management.Health practitioners might consider encouraging the inclusion of dairy products in the diets of individuals at risk of IBD, provided there are no contraindications, such as lactose intolerance or dairy allergies.Future studies should further elucidate the biological mechanisms underlying this association.Investigations could focus on differentiating the impacts of various dairy components, examining the role of the gut microbiome, and exploring genetic and environmental interactions.Additionally, longitudinal studies with larger, more diverse populations and standardized measures of dairy intake would help strengthen the evidence base and refine dietary guidelines for IBD prevention.

Figure 1 .
Figure 1.PRISMA flowchart of the studies included in the meta-analysis.

Figure 1 .
Figure 1.PRISMA flowchart of the studies included in the meta-analysis.

Figure 2 .
Figure 2. Meta-analysis of the association between dairy consumption and ulcerative colitis.

Figure 2 .
Figure 2. Meta-analysis of the association between dairy consumption and ulcerative colitis.

Figure 3 .
Figure 3. Meta-analysis of the association between dairy consumption and Crohn's disease.

Figure 3 .
Figure 3. Meta-analysis of the association between dairy consumption and Crohn's disease.

Table 1 .
Comparison between cases and controls in the case-control study.

Table 2 .
Association between dairy consumption and inflammatory bowel disease in the casecontrol study.

Table 3 .
Summary of the studies included in the meta-analysis.

Table 3 .
Summary of the studies included in the meta-analysis.

Table 4 .
Quality assessment of the studies included in the meta-analysis using the Newcastle-Ottawa Scale.