A new study finds that an artificial intelligence model can predict whether Crohn’s disease will recur after surgery.
A deep learning model trained to analyze histological images of surgical specimens accurately classified patients with and without Crohn’s disease recurrence, investigators report in The American Journal of Pathology.
According to researchers, more than 500,000 individuals in the United States have Crohn’s disease. Crohn’s disease is a chronic inflammatory bowel disease that damages the digestive system lining. It can cause digestive system inflammation, which may result in abdominal pain, severe diarrhea, exhaustion, weight loss, and malnutrition.
Many people end up needing surgery to treat their Crohn’s disease. Even after a successful operation, recurrence is common. Now, researchers are reporting that their AI tool is highly accurate at predicting the postoperative recurrence of Crohn’s disease. It also linked recurrence with the histology of subserosal adipose cells and mast cell infiltration.
Using an artificial intelligence (AI) tool that simulates how humans visualize and is trained to identify and categorize pictures, researchers created a model that predicts the postoperative recurrence of Crohn’s disease with high accuracy by evaluating histological images. The AI tool also identified previously unknown differences in adipose cells and substantial disparities in the degree of mast cell infiltration in the subserosa, or outer lining of the gut, when comparing individuals with and without disease recurrence. Elsevier’s The American Journal of Pathology published the findings.
The 10-year rate of postoperative symptomatic recurrence of Crohn’s disease, a chronic inflammatory gastrointestinal illness, is believed to be 40%. Although there are scoring methods to measure Crohn’s disease activity and the existence of postoperative recurrence, no scoring system has been devised to predict whether Crohn’s disease will return.
Sixty-eight patients with Crohn’s disease were classified according to the presence or absence of postoperative recurrence within two years. The investigators performed histological analysis of surgical specimens using deep learning EfficientNet-b5, a commercially available AI model designed to perform image classification. They achieved a highly accurate prediction of postoperative recurrence (AUC=0.995) and discovered morphological differences in adipose cells between the two groups. Credit: The American Journal of Pathology
“Most of the analysis of histopathological images using AI in the past have targeted malignant tumors,” explained lead investigators Takahiro Matsui, MD, Ph.D., and Eiichi Morii, MD, Ph.D., Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan. “We aimed to obtain clinically useful information for a wider variety of diseases by analyzing histopathology images using AI. We focused on Crohn’s disease, in which postoperative recurrence is a clinical problem.”
The research involved 68 Crohn’s disease patients who underwent bowel resection between January 2007 and July 2018. They were divided into two groups based on whether or not they had postoperative disease recurrence within two years after surgery. Each group was divided into two subgroups, one for training and the other for validation of an AI model. Whole slide pictures of surgical specimens were cropped into tile images for training, labeled for the presence or absence of postsurgical recurrence, and then processed using EfficientNet-b5, a commercially available AI model built to perform image classification. When the model was tested with unlabeled photographs, the findings indicated that the deep learning model accurately classified the unlabeled images according to the presence or absence of disease occurrence.
Following that, prediction heat maps were created to identify areas and histological features from which the machine learning algorithm could accurately predict recurrence. All layers of the intestinal wall were shown in the photos. The heatmaps revealed that the machine learning algorithm correctly predicted the subserosal adipose tissue layer. However, the model was less precise in other regions, such as the mucosal and proper muscular layers. Images with the greatest accurate predictions were taken from the non-recurrence and recurrence test datasets. The photos with the greatest predictive results all had adipose tissue.
Because the machine learning model achieved accurate predictions from images of subserosal tissue, the investigators hypothesized that subserosal adipose cell morphologies differed between the recurrence and the non-recurrence groups. Adipose cells in the recurrence group had a significantly smaller cell size, higher flattening, and smaller center-to-center cell distance values than those in the nonrecurrence group.
“These features, defined as ‘adipocyte shrinkage,’ are important histological characteristics associated with Crohn’s disease recurrence,” said Dr. Matsui and Dr. Morii.
The investigators also hypothesized that the differences in adipocyte morphology between the two groups were associated with some degree or type of inflammatory condition in the tissue. They found that the recurrence group had a significantly higher number of mast cells infiltrating the subserosal adipose tissue, indicating that the cells are associated with the recurrence of Crohn’s disease and the “adipocyte shrinkage” phenomenon.
To the investigators’ knowledge, these findings are the first to link postoperative recurrence of Crohn’s disease with the histology of subserosal adipose cells and mast cell infiltration. Dr. Matsui and Dr. Morii observed, “Our findings enable stratification by the prognosis of postoperative Crohn’s disease patients. Many drugs, including biologicals, are used to prevent Crohn’s disease recurrence, and proper stratification can enable more intensive and successful treatment of high-risk patients.”
Food antigens are thought to play a vital role in the initiation and perpetuation of Crohn’s disease (CD). The main purpose of this study was to evaluate the potential association of serum food specific IgG antibodies and small bowel (SB) inflammation in CD patients.
Methods
We conducted a prospective observational study with 96 CD patients. Demographic, disease-related data and inflammatory parameters were collected. Serum food IgG antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Capsule endoscopy was performed to detect SB inflammation quantified by the Lewis Score.
Results
Seventy-eight of (81.3%) CD patients were detected positive for at least one food-specific antibody. The five most prevalent food antibodies in CD patients were tomato, egg, corn, rice, and soybean. Patients with SB inflammation had a higher positive rate of food IgG antibodies (P = 0.010) and more IgG-positive food items (P = 0.010) than those without. Specifically, patients with SB inflammation were more likely to have positive food-specific IgG against egg (P = 0.014), corn (P = 0.014), and wheat (P = 0.048). Additionally, the number of positive food IgGs ≥ 3 and elevated ESR were independently associated with concurrent SB inflammation (P = 0.015 and P = 0.013, respectively).
Conclusion
Our study confirmed that CD patients with SB inflammation had a higher positive rate of food IgG antibodies and more IgG-positive food items. The number of food positive IgGs ≥ 3 and elevated ESR were independently associated with concurrent SB inflammation.
Slider with three content items shown per slide. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide
Abstract
Background/aims
Food antigens are thought to play a vital role in the initiation and perpetuation of Crohn’s disease (CD). The main purpose of this study was to evaluate the potential association of serum food specific IgG antibodies and small bowel (SB) inflammation in CD patients.
Methods
We conducted a prospective observational study with 96 CD patients. Demographic, disease-related data and inflammatory parameters were collected. Serum food IgG antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Capsule endoscopy was performed to detect SB inflammation quantified by the Lewis Score.
Results
Seventy-eight of (81.3%) CD patients were detected positive for at least one food-specific antibody. The five most prevalent food antibodies in CD patients were tomato, egg, corn, rice, and soybean. Patients with SB inflammation had a higher positive rate of food IgG antibodies (P = 0.010) and more IgG-positive food items (P = 0.010) than those without. Specifically, patients with SB inflammation were more likely to have positive food-specific IgG against egg (P = 0.014), corn (P = 0.014), and wheat (P = 0.048). Additionally, the number of positive food IgGs ≥ 3 and elevated ESR were independently associated with concurrent SB inflammation (P = 0.015 and P = 0.013, respectively).
Conclusion
Our study confirmed that CD patients with SB inflammation had a higher positive rate of food IgG antibodies and more IgG-positive food items. The number of food positive IgGs ≥ 3 and elevated ESR were independently associated with concurrent SB inflammation.
ArticleOpen access18 January 2021
Introduction
Crohn’s disease (CD) is a chronic, progressive and relapsing inflammatory disease characterized by transmural inflammation involving any part of the entire gastrointestinal tract. Relapsing bowel inflammation will accumulate structural bowel damage, which increases the risk of developing severe complications necessitating surgical intervention. Furthermore, small bowel (SB) involvement is associated with a poor prognosis and a higher likelihood of suffering complications [1, 2].Therefore, it is very important to closely monitor disease activity and achieve clinical persistent remission and mucosal healing to avoid the progression of bowel damage [3].
As to endoscopic assessment, ileocolonoscopy with biopsy is considered the first-line procedure to evaluate intestinal lesions among patients with CD. However, disease may be confined only to the SB in one-third of patients [4]. It is more challenging to evaluate the small bowel disease because ileocolonoscopy cannot reach the involved upper or medium bowel segment. Small bowel capsule endoscopy (SBCE) was introduced in 2000 to provide a reliable method to visualize directly the entire small bowel [5]. SBCE is considered a useful tool for the evaluation of suspected and established CD. SBCE has been shown to be more sensitive in detecting lesions in the proximal small bowel than magnetic resonance imaging enterography (MRE) and computed tomography enterography (CTE), with comparable accuracy for distal lesions [6,7,8]. It has been reported that SBCE is also useful for treatment guidance in patients with established CD [9]. Recently, a recent prospective cohort study also found that SBCE could predict both short-term and long-term risk of CD flare during follow-up [10]. Although noninvasive and generally well tolerated, SBCE is time consuming and costly to perform and entails the small but significant risk of capsule retention [11, 12].
A noninvasive inflammatory biomarker with good accuracy for diagnosing and monitoring CD is crucial in clinical practice. C-reactive protein (CRP) and Fecal calprotectin (FCP) are the most commonly used inflammatory biomarkers in clinical practice. However, the accuracy of CRP to predict intestinal inflammation was modest [13]. CRP can underestimate SB inflammation detected by SBCE in quiescent CD [14, 15], limiting its clinical utility for disease surveillance. FCP has a high accuracy in the evaluation of colonic inflammation, so it can be used as a reliable marker to predict disease relapse and guide treatment. However, accumulating evidence suggests that FCP shows a weak correlation with SBCE findings, limiting its utility in the prediction of SB inflammation [16,17,18].
Several studies have found that CD patients have a higher prevalence and titer of serum food-specific IgG antibodies than ulcerative colitis (UC) patients and healthy individuals [19,20,21]. Patients with SB involvement may be more likely to develop food-specific IgG antibodies than patients without small bowel involvement [20]. A possible explanation is that intestinal barrier dysfunction allows food antigens to enter the submucosa and contact with immune cells directly, leading to the production of food antibodies. Therefore, food-specific antibodies may serve as a potential marker for predicting SB inflammation. The purpose of this study was to investigate the prevalence of food specific IgG antibodies in CD patients. We also sought to confirm the association between food-specific IgG antibodies and SB disease activity evaluated by SBCE.
Material and methods
The study population
From April 2017 to April 2019, CD patients with known SB involvement were prospectively recruited for this study. This study was conducted at the First Affiliated Hospital of Fujian Medical University, a tertiary care center for the management of CD in Fujian Province, China. The diagnosis of CD was established based on a combination of clinical, endoscopic, radiological, and histological criteria [22]. All patients signed an informed consent, and the study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University, China, in accordance with the Declaration of Helsinki.
The inclusion criteria included: a previous diagnosis of CD with SB involvement; age older than 14 years; and willingness to undergo CTE or MRE at enrollment. The exclusion criteria were: inability to understand or unwillingness to provide informed consent; serious liver, kidney, brain or cardio-respiratory comorbidities; difficulty in swallowing, history of dysphagia or aspirations; use of non-steroidal anti-inflammatory drugs within the previous month; definite intestinal stricture identified by imaging or bowel obstruction at enrollment.
Sample size estimation
A non-probability convenience sampling method was used to recruit CD patients. The sample size was calculated using PASS version 11.0 (NCSS Statistical Software, Kaysville, UT, United States). According to previous reports [19,20,21], the estimated positive rate of food-specific antibodies in CD patients is approximately 80%. The sample size obtained was 96 at a margin of error of 5% and a confidence level of 95%.
Data collection
The disease activity in CD patients was scored by the CD activity index score (CDAI) [23]. Demographic data, body mass index (BMI), smoking status, history of intestinal surgery, disease duration, disease location and behavior were collected for each patient at the time of enrollment. Information about medical treatment was also collected.
At enrollment, peripheral blood was collected from each patient for analysis of total white blood cell count, eosinophil ratio, hemoglobin, platelet count, and inflammatory markers, such as CRP and erythrocyte sedimentation rate (ESR). A stool sample was also collected to determine FCP using a commercially available colloidal gold immunofiltration assay (Wizbiotech, Xiamen, China).
Serum food-specific IgG antibodies test
A commercially available enzyme-linked immunosorbent assay (ELISA) kit (HOB Biotech Group Corp., Suzhou, China) was used to quantitatively determin serum IgG antibodies against 14 common food-derived antigens, including beef, codfish, chicken, corn, egg, crab, mushroom, milk, rice, pork, shrimp, soybean, wheat and tomato. The whole detection process was carried out in accordance with the manufacturer’s instructions, and the final results were obtained by the ELISA plate reader (Infinite F50, TECAN, Männedorf, Switzerland) at an absorbance of 450 nm.
A food IgG concentration less than 50 U/mL was considered negative (Grand 0). Levels of 50–100 U/mL, 100–200 U/mL, and greater than 200 U/mL were classified as mild sensitivity (Grade 1+), moderate sensitivity (Grade 2+) and high sensitivity (Grade 3+), respectively.
Capsule endoscopy examinations
MRE or CTE were performed in all patients before CE examination to detect severe intestinal stricture and avoid capsule retention. On the day before examination, patients underwent bowel preparation with 2-L of 6.8% polyethylene glycol electrolyte oral solution (Shutaiqing, Staidson Beijing Biopharmaceuticals Co., Ltd., Beijing, China). After a 12-h overnight fast, patients swallowed the capsule (Jinshan Science & Technology Co., Ltd., Chongqing, China). After 8–10 h of recording, the images were downloaded to the OMOM capsule endoscopy workstation (Jinshan Science & Technology Co., Ltd., Chongqing, China).
All images were reviewed carefully by two experienced gastroenterologists blinded to the study design and clinical data of the patients. SB inflammation was quantified using the Lewis score (LS) [24]. LS is considered as SB mucosal healing or no clinical significant inflammation if lower than 135 points, mild inflammation 135–790 points, and severe inflammation 790 points [24].
Statistical analysis
Data were analyzed using SPSS software version 22.0 (IBM, Armonk, New York, USA). Continuous variables with normal distribution were presented as mean ± standard deviation (SD) and continuous variables with non-normal distribution were presented as median ± interquartile range. Either the Student’s t test or the Mann–Whitney U-test was used for comparisons between two groups in term of continuous variables. Variance was compared with the F-test. Categorical data were presented as counts, and assessed using Fisher’s exact test or the χ2 test. Univariate and multivariate logistic regression analysis were used to identify the association between SB inflammation and clinical characteristics and food IgGs. A P value < 0.05 was considered statistically significant.
Results
Clinical and demographic characteristics of the included patients
A total of 96 patients with CD were finally included in this study. The baseline clinical and demographic characteristics of the included patients are shown in Table 1. The median age of patients was 25 (18, 31) years and 63 (66%) were men. The median disease duration from the time of disease onset to study enrollment was 24 (10, 48) months. 21/96 (21.9%) were in the active stage (CDAI ≥ 150) at entry. Thirty-seven (38.5%) had elevated CRP (>10 mg/dL), and twenty-one (21.9%) had elevated FCP (>100 µg/g). SBCE examinations demonstrated SB inflammation in 71(74%) patients (LS ≥ 135).Table 1 Baseline characteristics of the included Crohn’s disease patients.
The levels of serum food-specific IgG antibodies of CD patients against fourteen common food antigens are shown in Table 2. In this study, at least one food antibody was detected positive in 78 (81.3%) patients with CD, and among them 15.6% (15/96), 15.6% (15/96), and 50.0% (48/96) of patients had one, two and more than two types of food antibodies respectively. The mean number of food antibodies was 3.0 ± 2.5. The five most prevalent food antibodies in CD patients were tomato (58/96, 60.4%), egg (51/96, 53.1%), corn (51/96, 53.1%), rice (43/96, 44.8%), and soybean (23/96, 24.0%).Table 2 Distribution of positive food IgG antibodies in Crohn’s disease patients.
Comparison of clinical characteristics between patients with and without small bowel inflammation
As shown in Table 3, there was no statistically significant difference between CD patients with and without SB inflammation with respect to age, gender, BMI, disease location, disease duration, allergic disease history, current treatment with 5-amino salicylic acids (5-ASAs), steroids or immunosuppressants. Moreover, statistical analysis failed to show any significant difference between patients with and without SB inflammation in terms of the median CDAI (49.0 vs. 66.2, respectively; P = 0.233) and serum CRP levels (4.18 vs.8.39, respectively; P = 0.133). Among patients with SB inflammation, 17 (23.9%) had a CDAI ≥ 150, and 30 (42.3%) had an elevated CRP level. By contrast, 4 (16.0%) patients without SB inflammation had a CDAI ≥ 150 and 7 (28.0%) had an elevated CRP level (P > 0.05 for both comparisons). Conversely, patients with SB inflammation tended to have a higher incidence rate of perianal involvement (70.4 vs 48.0%, P = 0.044) and higher inflammatory activity with an ESR > 20 mm/h (69.0 vs 36.0%, P = 0.004), compared to patients without SB inflammation.Table 3 Demographic and Clinical characteristics in Crohn’s disease patients according to the presence of small bowel inflammation.
Comparison of food-specific IgG antibodies in sera of patients with and without small bowel inflammation
As shown in Table 4, CD patients with SB inflammation showed a higher positive rate of food IgG than those without (87.3vs 64.0%, P = 0.010). The mean number of food positive IgG items in patients with SB inflammation was higher than patients without SB inflammation (3.4 vs 1.9, P = 0.010). Patients with SB inflammation were more likely to develop more than two different food IgGs than patients without SB inflammation (57.7 vs 28.0%, P = 0.011). Specifically, patients with SB inflammation were prone to have a higher positive rate of food specific IgG against egg (60.6 vs 32.0%, P = 0.014), corn (60.6vs 32.0%, P = 0.014), and wheat (21.1 vs 4.0%, P = 0.048), compared to those without SB inflammation. Furthermore, patients with SB inflammation were more likely to have positive food IgG against rice with a marginally significance than those without SB inflammation (50.7 vs 28.0%, P = 0.050). No significant difference in food IgGs against chicken (P = 0.173), crab (P = 0.260), shrimp (P = 0.435), codfish (P = 0.467), pork (P = 0.396), milk (P = 0.165), soybean (P = 0.278), tomato (P = 0.140), or mushroom (P = 0.752) were observed between patients with and without SB inflammation. Figure 1 shows the distribution of positive food antibodies in CD patients with and without SB inflammation.Table 4 Comparison of serum food-specific IgG antibodies positivity between patients with and without small bowel inflammation.
Fig. 1: Distribution of positive food antibodies in Crohn’s disease patients with and without small bowel inflammation.
Association between small bowel inflammation and clinical characteristics and food IgGs antibodies in CD patients
As shown in Table 5, univariate logistic regression analysis indicated that SB inflammation was significantly associated with age, perianal involvement, biologicals treatment, elevated ESR and number of positive food IgGs ≥ 3. Multivariate analysis revealed that biologicals treatment (odds ratio [OR] = 3.945, 95% confidence interval [CI] 1.333–11.680, P = 0.013), elevated ESR (OR = 3.587, 95% CI, 1.278–10.068, P = 0.015) and number of positive food IgGs ≥ 3 (OR = 3.814, 95% CI 1.284–11.333, P = 0.016) remained significantly and independently associated with SB inflammation.Table 5 Results of univariate and multivariate analyses examining factors associated with small bowel inflammation in Crohn’s disease patients.
Our prospective study shows that food-specific IgG antibodies are highly prevalent in CD patients. The five most prevalent food antibodies in CD patients are tomato, egg, corn, rice, and soybean. Interestingly, serum food IgG antibodies were found to be associated with concurrent SB inflammation evaluated by SBCE. Patients with SB inflammation had a higher positive rate of food IgG antibodies and more IgG-positive food items. Additionally, equal or more than three IgG-positive food items and elevated ESR were independent predictors of SB inflammation.
Most (81.3%) of CD patients were detected positive for at least one food specific antibody, which is consistent with previous studies [19,20,21]. This result is not surprising because increased intestinal permeability is a typical feature of CD patients, which facilitates food antigens into the circulation and then stimulates the production of relevant antibodies. More than two different food specific antibodies were detected positive in half of the patients in present study. The five most prevalent food antibodies in CD patients were tomato (60.4%), egg (53.1%), corn (53.1%), rice (44.8%), and soybean (24.0%), similar to a previous study [21]. Wang and colleagues [25] recently reported that CD patients exhibited more intense immune response to food antigens than UC and controls, and the number of food IgG-positive items could be used to discriminate CD from UC and healthy controls, with high diagnostic value.
Previous studies have shown that CD patients with SB involvement are significantly associated with lactose maldigestion [26, 27]. Notwithstanding, ref. [20] reported that patients with only small intestine involved were prone to have a higher positive rate of food antibodies (82.5%) with an unremarkable statistical difference. When patients were regrouped, those with small bowel involved had a significantly higher positive rate than those without (79.7 vs. 60.5%, p = 0.005). However, no significant correlation was found between positive rates of food-specific IgG and disease location in CD patients in the studies by ref. [19] and ref. [21]. This may be due to the fact that disease location determined according to the Montreal classification cannot distinguish active small bowel mucosal inflammation. LS based on CE findings may be more precise for reflecting the real state of small bowel. In our study, we used LS to identify whether patients had active SB inflammation. Higher positive rates of food IgG antibodies and more IgG-positive food items were found in patients with SB inflammation (LS ≥ 135) in the present study. It is not surprising that intestinal stenosis, food indigestion and increased intestinal mucosa permeability are commonly presented in patients with small intestinal CD, which might allow more chances for food antigens to be recognized by the immune system and produce specific antibodies. The types of food IgG antibodies may differ owing to the diversity of diet habits in different regions, while the number of food-positive antibodies may be more precise to reflect the current bowel state. In this study, we found that patients with active SB disease had a higher positive rate of food antibodies, and more food-positive items. The number of food-positive items (≥3 positive) was an independent predictor of SB inflammation. This finding may provide a noninvasive method for diagnosing and monitoring CD in clinical practice.
Our study also has several main drawbacks. Firstly, it was a single center, cross-sectional analysis that included a relatively small number patients. Secondly, this research was not a follow-up study to investigate whether improvement of SB disease severity could be paralleled by a reduction in the positive rate of food-specific IgG after medical treatment. Thirdly, children with CD were excluded in our study. Additionally, the study did not investigate the patient’s dietary habits, which may have an impact on the types and titers of food IgG.
In conclusion, our study confirms that serum food-specific IgG antibodies are highly prevalent in CD patients. Notably, CD patients with SB inflammation have a higher positive rate of food IgG antibodies and more IgG-positive food items. The number of food-positive IgGs (≥3) is independently associated with concurrent SB inflammation. This finding may provide a convenient and noninvasive method for predicting SB inflammation in clinical practice.
Described in a paper in Science Advances, these nanoparticles can fight harmful molecules, called reactive oxygen species (ROS), that can worsen IBD in excessive amounts. They are made from poly(propylene sulfide) – a polymer that can neutralize ROS – and hyaluronic acid, a compatible compound commonly used in medicine.
The nanoparticles – the researchers call them “backpacks” – can be attached to probiotics, which deliver them to the gut.
“Due to the colonizing property of probiotics in colon tissues, the nanoparticles could be delivered to colon tissues by probiotics and released slowly,” says study author Quanyin Hu, PhD, a biomedical engineer and assistant professor at the University of Wisconsin-Madison School of Pharmacy.
This helps give the nanoparticles time to bring the ROS level back down to normal. But that’s only part of the IBD treatment the researchers envision.
Signs Your IBD Is Getting Worse
With mild IBD, most people feel better with medication, but there are severe cases and symptoms to look out for.
The technology builds on a previous development from Hu and his team – a protective probiotic shell coating. The coating, which is about 330 nanometers thick, helps probiotics survive long enough to establish and multiply in the gut.
“The harsh environment of gastric acid and bile salt would kill most probiotics,” Hu says. “Moreover, antibiotics usually used in inflammatory bowel disease treatment also harm probiotic growth.”
Early results are promising, he says. Mice with IBD that received the full treatment – combining the ROS-targeting nanoparticles with the coated probiotics – had fewer IBD symptoms, like less weight loss and colon shortening, than those treated with the encapsulated probiotics alone.
By attacking the disease on multiple fronts – reducing the ROS and improving the balance of gut microbiota – a healthy gut environment could be restored, Hu says. In other words: “[It] might be possible to finally cure inflammatory bowel disease.”
Nanotechnology offers all kinds of unique advantages over traditional IBD treatments, he says. Nanoparticles can be designed to target specific tissues, like colon tissues. And compared to small molecules, they can circulate throughout the body longer, so they have more time to build up and do their job.
The next steps will be to test the treatment in large animals and “to develop a stable formulation that can be stored for a long time and produced in a scalable and economical manner,” Hu says.
Current IBD treatments “can only relieve symptoms,” not cure the disease, he says.
“This study is our first try to fundamentally treat inflammatory bowel disease by recovering a healthy microenvironment in the intestines, and our preliminary data demonstrated that this strategy is delivering promises to pave a new treatment strategy for IBD,” Hu says.
Dog ownership and close interactions with these pets in early childhood could help prevent later development of Crohn’s disease, according to data presented at Digestive Disease Week 2022.
“Our study seems to add to others that have explored the ‘hygiene hypothesis’ which suggests that the lack of exposure to microbes early in life may lead to lack of immune regulation toward environmental microbes,” Williams Turpin, PhD, research associate at Mount Sinai Hospital and the University of Toronto, said in a press release.
To determine whether environmental factors in different age groups affect the future risk for CD, Turpin and colleagues used an environmental risk assessment questionnaire to collect information from healthy first-degree relatives of patients with CD (n = 4,300) who were enrolled in the Genetic, Environmental and Microbial (GEM) project from Crohn’s and Colitis Canada.
The researchers examined questionnaire responses alongside historical data collected at the time of recruitment to assess for multiple environmental factors, including living on farms, consumption of unpasteurized milk and well water, family size, number of bathrooms in the home and pet ownership, specifically cats and dogs. They also analyzed approximate age at the time of each environmental exposure: aged younger than 1 year, 2 to 4 years and 5 to 15 years.
Turpin and colleagues used Cox proportional hazard models to identify exposures linked to future CD development, with regression models used in a secondary analysis to ascertain the relationship of exposures with biological factors previously associated with CD risk. These factors included intestinal permeability using urinary fractional excretion of lactulose to mannitol ratio (LMR; abnormal if 0.025), subclinical inflammation using fecal calprotectin (FCP) and fecal microbiome composition and diversity using 16S rDNA sequencing.
According to study results, living with a dog between the ages of 2 to 4 years (HR = 0.63; 95% CI, 0.44-0.99) and a large family size (>3 individuals) in the first year of life (HR = 0.36; 95% CI, 0.18-0.72) were associated with a lower risk for developing CD.
Although Turpin and colleagues found that family size in the first year was not linked to altered LMR, FCP or microbiome composition and diversity, dog ownership during the ages of 2 to 4 years (OR = 0.77, 95% CI, 0.60-0.93) significantly correlated with normal LMR. Researchers determined dog ownership at other ages consistently showed a significant association with normal LMR values, yet no link was found between dog ownership and FCP, microbiome composition and diversity.
“We did not see the same results with cats, though we are still trying to determine why,” Turpin said in the release. “It could potentially be because dog owners get outside more often with their pets or live in areas with more green space, which has been shown previously to protect against Crohn’s.”
Inflammatory bowel diseases (IBD), namely, Crohn’s disease (CD) and ulcerative colitis (UC), are lifelong and incurable chronic inflammatory diseases affecting 6.8 million people worldwide. By 2030, the prevalence of IBD is estimated to reach 1% of the population in Western countries, and thus there is an urgent need to develop effective therapies to reduce the burden of this disease. Microbiome dysbiosis is at the heart of the IBD pathophysiology, and current research and development efforts for IBD treatments have been focused on gut microbiome regulation. Diet can shape the intestinal microbiome. Diet is also preferred over medication, is safe, and has been proven to be an effective strategy for the management of IBD. Therefore, although often overlooked, dietary interventions targeting the microbiome represent ideal treatments for IBD. Here, I summarize the latest research on diet as a treatment for IBD from infancy to adulthood, compile evidence of the mechanisms of action behind diet as treatment, and, lastly, provide insights into future research focusing on culturally tailored diets for ethnic minority groups with increased incidence of IBD yet underrepresented in nutrition research.
FUTURE CONSIDERATIONS: CULTURALLY TAILORED DIETARY INTERVENTION FOR UNDERREPRESENTED IBD PATIENTS
Historically, IBD is known to affect more people of Caucasian origin than other ethnic groups; however, there is emerging evidence that the prevalence of IBD in Hispanics may be increasing, along with that in the general U.S. population (191, 192). Currently, Hispanics and Latinx account for over 18% of the U.S. population (193, 194). Foreign-born Hispanics in the United States are diagnosed at an older age and present more cases of ulcerative colitis than U.S.-born Hispanics and non-Hispanic whites (195). A meta-analysis also showed that Crohn’s disease behavior between non-Hispanic whites and Hispanics is similar, but Hispanics had a tendency of less upper gastrointestinal involvement (196). Growing evidence demonstrates that Hispanics change their diet upon immigration to the United States, reporting low consumption of total vegetables, legumes, whole grains, and sea plant protein (197). Similarly, Asians, the fastest-growing racial group in the United States (194), have been increasingly diagnosed with IBD in the United States and around the world (198, 199). Recent studies have demonstrated that Asians exhibit different IBD clinical phenotypes, including ocular manifestations and more fistulizing perianal Crohn’s disease, than their Caucasian counterparts (198, 199). A comprehensive study confirmed that U.S. immigrants (of Asian origins) suffer an immediate loss of gut microbiome diversity along with a reduction of microbial capacity for fiber degradation (200). Instead, the microbiome of Asian immigrants is characterized by an enrichment of United States-associated bacterial strains displacing native strains along with the genetic capabilities (200). Like Hispanics, Asian immigrants rapidly change their diet upon arrival in the United States, which partially explains the shift in the microbiome seen in this population (200).
The lack of inclusion of underrepresented ethnic minorities in IBD studies has ignited efforts led by patient advocates and IBD specialists of South Asian descent, such as the South Asian IBD Alliance (SAIAI) (201). The alliance aims to promote “the need for culturally competent, evidence-based, patient-centric care via advocacy, education, and training” to improve the care of South Asian patients with IBD across the globe (201).
Despite the increased incidence of IBD in these minority groups, research aimed at these populations, including research on diet as therapy for IBD, is lacking. In addition, ethnic minority groups frequently experience low-quality care at hospitals due to a combination of factors, including lack of insurance, economic and language barriers, and racial bias in pain assessment and treatment recommendations, to name a few (202–204). Culturally tailored interventions can close the gap in the paucity of research and help improve health care equity and quality for minority populations with IBD (205–208).
Culturally tailored interventions are frequently implemented in the context of behavioral health trials, with proven success to encourage healthy behaviors (including healthy eating) and to address health disparities affecting minority groups with chronic diseases (206, 209–211). A recent meta-analysis of 33 culturally tailored trials highlighted three key aspects of successful interventions (212), as follows. (i) “Linguistic tailoring” aims to address not only the language but also the literacy needs of the target population. Moreover, linguistic tailoring should also consider the inclusion of bilingual staff to remove language barriers between patients/participants, research staff, and health care providers. (ii) “Sociocultural tailoring” aims to incorporate cultural values, unique experiences, religious beliefs, and behaviors of the target group. (iii) “Constituent-involving strategies” aims to build on a sense of collectivism and existing kinship networks by including members of the target community in the research and intervention activities, from actively participating in the study design to their involvement in delivering the intervention (212, 213).
In the case of nutrition, culturally tailored interventions also need to be adapted to the unique culinary preferences and access to foods of the target community. By doing so, the interventions will be relevant to understudied minority groups with high IBD prevalence and in need of attainable strategies to improve their quality of life.
Another challenge for culturally tailored dietary interventions is long-term compliance. Examples from data about dietary recommendations in Australia (214) demonstrate that it is not enough to solely suggest that people consume more beneficial foods. Therefore, culturally tailored dietary interventions also need to provide patients with culinary training aimed at building skills and confidence in food preparation in the kitchen
ARYAN'S BLOG 
