Probiotics for inflammatory bowel diseases: a promising adjuvant treatment

Inflammatory bowel diseases (IBD) encompass ulcerative colitis (UC), Crohn’s disease (CD) and indeterminate colitis (IC), characterising chronic inflammation in the gastrointestinal tract, associated with changes in the immune system and in the intestinal microbiota. Thus, probiotics may offer an alternative or adjuvant approach to conventional therapy. The present review aims to summarise the mechanisms of action of probiotics in IBD and their therapeutic effects. Most of the studies suggest that probiotics are effective in the treatment of UC, especially when several strains are concomitantly administered. Species of Lactobacillus and Bifidobacterium genres are the most commonly used, and some studies even indicate that it is possible to replace medical therapy with probiotic supplementation. Regarding CD, the results of clinical trials are controversial and do not support the use of probiotics in this disease. In conclusion, probiotic supplementation is a promising adjuvant treatment in UC, but not in CD.     

Depression and anxiety in people with inflammatory bowel disease

STUDY OBJECTIVE—To determine whether depression or anxiety co-occurs with ulcerative colitis (UC) or Crohn's disease (CD) more often than expected by chance, and, if so, whether the mental disorders generally precede or follow the inflammatory bowel diseases (IBD).
DESIGN—Nested case-control studies using a database of linked hospital record abstracts.
SETTING—Southern England.
MAIN RESULTS—Both depression and anxiety preceded UC significantly more often than would be predicted from the control population's experience. The associations were strongest when the mental conditions were diagnosed shortly before UC, although the association between depression and UC was also significant when depression preceded UC by five or more years. Neither depression nor anxiety occurred before CD more often than expected by chance. However, depression and anxiety were significantly more common after CD; the associations were strongest in the year after the initial record of CD. UC was followed by anxiety, but not by depression, more often than expected by chance and, again, the association was strongest within one year of diagnosis with UC.
CONCLUSIONS—The concentration of risk of depression or anxiety one year or less before diagnosis with UC suggests that the two psychiatric disorders might be a consequence of early symptoms of the as yet undiagnosed gastrointestinal condition. The data are also, however, compatible with the hypothesis that the psychiatric disorders could be aetiological factors in some patients with UC. Most of the excess anxiety or depression diagnosed subsequent to diagnosis of IBD occurs during the year after IBD is diagnosed and the probable explanation is that the mental disorders are sequelae of IBD.


Keywords: record linkage; ulcerative colitis; Crohn's disease; anxiety; depression     

Vitamin D in Inflammatory Bowel Diseases. Mechanisms of Action and Therapeutic Implications

(1) Background: Vitamin D is an immunoregulatory factor influencing intestinal homeostasis. Recent evidence supports a central role of this micronutrient in the course of Inflammatory Bowel Diseases (IBD). This narrative review aims to provide a general overview of the possible biological mechanisms of action of vitamin D and its therapeutic implications in IBD. (2) Methods: A systematic electronic search of the English literature up to October 2021 was performed using Medline and the Cochrane Library. Only papers written in English that analyzed the role of vitamin D in IBD were included. (3) Results: In vitro and animal studies reported that vitamin D signaling improves epithelial barrier integrity regulating the expression of several junctional proteins, defensins, and mucins, modulates the inflammatory response, and affects gut microbiome composition. Recent studies also suggest that vitamin D deficiency is highly prevalent among IBD patients and that low serum levels correlate with disease activity and, less clearly, with disease course. (4) Conclusions: An increasing body of evidence suggests some role of vitamin D in the pathophysiology of IBD, nonetheless the underlying mechanisms have been so far only partially elucidated. A strong correlation with disease activity has been reported but its implication in the treatment is still undefined. Thus, studies focused on this issue, the definition of vitamin D levels responsible for clinical effects, and the potential role of vitamin D as a therapeutic agent are strongly encouraged.     

Therapeutic Implications of Diet in Inflammatory Bowel Disease and Related Immune-Mediated Inflammatory Diseases

Despite being a focal issue to patients, the effect of diet on adult inflammatory bowel disease (IBD) remains underexplored with limited guidance. While promising clinical trials are currently underway, there is a need for further evidence-based recommendations. As such, we summarize the current evidence on various diets used in the treatment of IBD and also explore the potential applications of dietary data from related immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis and psoriasis, to provide additional information to inform IBD providers. To date, there have been multiple diets investigated as adjunctive therapy in IBD, but many associated studies are small, non-randomized, and not controlled. Mediterranean, vegetarian/vegan, and reduced-calorie/fasting diets have been studied and have shown some positive results in other IMIDs, which may suggest potential applicability to those with IBD, but larger, well-designed clinical trials are needed for further guidance. Gluten-free and low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP)diets do not appear to have an impact on IBD disease activity, but low FODMAP may potentially be helpful for those with concurrent functional gastrointestinal symptoms. Specific carbohydrate diets have been mainly assessed in children but show some potential in small adult studies.     

Gut Microbiota in Non-Alcoholic Fatty Liver Disease Patients with Inflammatory Bowel Diseases: A Complex Interplay

The intestinal microbiota represents the microbial community that colonizes the gastrointestinal tract and constitutes the most complex ecosystem present in nature. The main intestinal microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucromicrobia, with a clear predominance of the two phyla Firmicutes and Bacteroidetes which account for about 90% of the intestinal phyla. Intestinal microbiota alteration, or dysbiosis, has been proven to be involved in the development of various syndromes, such as non-alcoholic fatty liver disease, Crohn’s disease, and ulcerative colitis. The present review underlines the most recurrent changes in the intestinal microbiota of patients with NAFLD, Crohn’s disease, and ulcerative colitis.     

Intestinal Taxa Abundance and Diversity in Inflammatory Bowel Disease Patients: An Analysis including Covariates and Confounders

Intestinal dysbiosis has been widely documented in inflammatory bowel diseases (IBDs) and is thought to influence the onset and perpetuation of gut inflammation. However, it remains unclear whether such bacterial changes rely in part on the modification of an IBD-associated lifestyle (e.g., smoking and physical activity) and diet (e.g., rich in dairy products, cereals, meat and vegetables). In this study, we investigated the impact of these habits, which we defined as confounders and covariates, on the modulation of intestinal taxa abundance and diversity in IBD patients. 16S rRNA gene sequence analysis was performed using genomic DNA extracted from the faecal samples of 52 patients with Crohn’s disease (CD) and 58 with ulcerative colitis (UC), which are the two main types of IBD, as well as 42 healthy controls (HC). A reduced microbial diversity was documented in the IBD patients compared with the HC. Moreover, we identified specific confounders and covariates that influenced the association between some bacterial taxa and disease extent (in UC patients) or behaviour (in CD patients) compared with the HC. In particular, a PERMANOVA stepwise regression identified the variables “age”, “eat yogurt at least four days per week” and “eat dairy products at least 4 days per week” as covariates when comparing the HC and patients affected by ulcerative proctitis (E1), left-sided UC (distal UC) (E2) and extensive UC (pancolitis) (E3). Instead, the variables “age”, “gender”, “eat meat at least four days per week” and “eat bread at least 4 days per week” were considered as covariates when comparing the HC with the CD patients affected by non-stricturing, non-penetrating (B1), stricturing (B2) and penetrating (B3) diseases. Considering such variables, our analysis indicated that the UC extent differentially modulated the abundance of the Bifidobacteriaceae, Rikenellaceae, Christensenellaceae, Marinifilaceae, Desulfovibrionaceae, Lactobacillaceae, Streptococcaceae and Peptostreptococcaceae families, while the CD behaviour influenced the abundance of Christensenellaceae, Marinifilaceae, Rikenellaceae, Ruminococcaceae, Barnesiellaceae and Coriobacteriaceae families. In conclusion, our study indicated that some covariates and confounders related to an IBD-associated lifestyle and dietary habits influenced the intestinal taxa diversity and relative abundance in the CD and UC patients compared with the HC. Indeed, such variables should be identified and excluded from the analysis to characterize the bacterial families whose abundance is directly modulated by IBD status, as well as disease extent or behaviour.     

Does Drinking Coffee and Tea Affect Bone Metabolism in Patients with Inflammatory Bowel Diseases?

Patients suffering from Crohn’s disease and ulcerative colitis are at higher risk of osteoporosis due to lower bone mineral density. Risk factors of osteoporosis are divided into unmodifiable, namely, age, gender, genetic factors, as well as modifiable, including diet, level of physical activity, and the use of stimulants. Coffee and tea contain numerous compounds affecting bone metabolism. Certain substances such as antioxidants may protect bones; other substances may increase bone resorption. Nevertheless, the influence of coffee and tea on the development and course of inflammatory bowel diseases is contradictory.     

The Usefulness of Serum Vitamin D Levels in the Assessment of IBD Activity and Response to Biologics

The main role of vitamin D is calcium homeostasis and bone metabolism, although its activity as an immuno-modulator and its anti-inflammatory effect is well-known. Low blood vitamin D levels are common among patients with inflammatory bowel disease (IBD). Whether low vitamin D levels could affect the disease activity or it is an effect of a worse condition of the disease is still unclear. This study aimed to investigate the role of blood vitamin D levels to identify the clinical, endoscopic, and histological activity in a cohort of patients with ulcerative colitis (UC) or Crohn’s disease (CD) on therapy with biological drugs. In this retrospective cohort study, 50 IBD patients (24 UC and 26 CD) that underwent colonoscopy from January 2017 to January 2020 with a concomitant serological evaluation of vitamin D were included. Patients with clinical, endoscopic, and histological activity and those who lost their clinical response to the biological drug had lower vitamin D levels compared to patients in remission or patients that did not change therapeutic regimens. A receiver operating characteristic (ROC) analysis and Youden’s Index were performed to assess the optimal vitamin D levels to identify patients with the active disease. The ROC analysis showed an area under the curve (AUC) of 0.709 (p = 0.005; confidence interval (CI): 0.564–0.829), 0.769 (p < 0.001; CI: 0.628–0.876), and 0.810 (p < 0.001; CI: 0.670–0.910) for the clinical, endoscopic, and histological outcomes, respectively. The optimal vitamin D cut-off was ≤25 ng/mL. The vitamin D level is an additional useful tool in the evaluation of IBD patients with good accuracy to predict their endoscopic and histological activity and clinical response to biologics.     

Long-Term Dietary Patterns Are Reflected in the Plasma Inflammatory Proteome of Patients with Inflammatory Bowel Disease

Diet plays an important role in the development and progression of inflammatory bowel disease (IBD, comprising Crohn’s disease (CD) and ulcerative colitis (UC)). However, little is known about the extent to which different diets reflect inflammation in IBD beyond measures such as faecal calprotectin or C-reactive protein. In this study, we aimed to unravel associations between dietary patterns and circulating inflammatory proteins in patients with IBD. Plasma concentrations of 73 different inflammation-related proteins were measured in 454 patients with IBD by proximity extension assay (PEA) technology. Food frequency questionnaires (FFQ) were used to assess habitual diet. Principal component analysis (PCA) was performed to extract data-driven dietary patterns. To identify associations between dietary patterns and plasma proteins, we used general linear models adjusting for age, sex, BMI, plasma storage time, smoking, surgical history and medication use. Stratified analyses were performed for IBD type, disease activity and protein intake. A high-sugar diet was strongly inversely associated with fibroblast growth factor-19 (FGF-19) independent of IBD type, disease activity, surgical history and deviance from recommended protein intake (false discovery rate (FDR) < 0.05). Conversely, a Mediterranean-style pattern was associated with higher FGF-19 levels (FDR < 0.05). A pattern characterised by high alcohol and coffee intake was positively associated with CCL11 (eotaxin-1) levels and with lower levels of IL-12B (FDR < 0.05). All results were replicated in CD, whereas only the association with FGF-19 was significant in UC. Our study suggests that dietary habits influence distinct circulating inflammatory proteins implicated in IBD and supports the pro- and anti-inflammatory role of diet. Longitudinal measurements of inflammatory markers, also postprandial, are needed to further elucidate the diet–inflammation relationship.     

Simple Clinical Screening Underestimates Malnutrition in Surgical Patients with Inflammatory Bowel Disease—An ACS NSQIP Analysis

The present large scale study aimed to assess the prevalence and consequences of malnutrition, based on clinical assessment (body mass index and preoperative weight loss) and severe hypoalbuminemia (<3.1 g/L), in a representative US cohort undergoing IBD surgery. The American College of Surgeons National Quality improvement program (ACS-NSQIP) Public User Files (PUF) between 2005 and 2018 were assessed. A total of 25,431 patients were identified. Of those, 6560 (25.8%) patients had severe hypoalbuminemia, 380 (1.5%) patients met ESPEN 2 criteria (≥10% weight loss over 6 months PLUS BMI < 20 kg/m² in patients <70 years OR BMI < 22 kg/m² in patients ≥70 years), and 671 (2.6%) patients met both criteria (severe hypoalbuminemia and ESPEN 2). Patients who presented with malnutrition according to any of the three definitions had higher rates of overall, minor, major, surgical, and medical complications, longer LOS, higher mortality and higher rates of readmission and reoperation. The simple clinical assessment of malnutrition based on BMI and weight loss only, considerably underestimates its true prevalence of up to 50% in surgical IBD patients and calls for dedicated nutritional assessment.     

Dietary Patterns and the Risk of Inflammatory Bowel Disease: Findings from a Case-Control Study

Scientific evidence shows that dietary patterns are associated with the risk of IBD, particularly among unhealthy and Western dietary patterns. However, Western dietary patterns are not exclusive to Western countries, as Jordanians are steadily moving towards a Western lifestyle, which includes an increased consumption of processed foods. This study aims to investigate the association between dietary patterns and the risk factors for IBD cases among Jordanian adults. This case-control study was conducted between November 2018 and December 2019 in the largest three hospitals in Jordan. Three hundred and thirty-five Jordanian adults aged between 18–68 years were enrolled in this study: one hundred and eighty-five IBD patients who were recently diagnosed with IBD (n = 100 for ulcerative colitis (UC) and n = 85 for Crohn’s disease (CD)) and 150 IBD-free controls. Participants were matched based on age and marital status. In addition, dietary data was collected from all participants using a validated food frequency questionnaire. Factor analysis and principal component analysis were used to determine the dietary patterns. Odds ratios (OR) and their 95% confidence interval (CI) were calculated using a multinomial logistic regression model. Two dietary patterns were identified among the study participants: high-vegetable and high-protein dietary patterns. There was a significantly higher risk of IBD with high-protein intake at the third (OR, CI: 2.196 (1.046–4.610)) and fourth (OR, CI: 4.391 (2.67–8.506)) quartiles in the non-adjusted model as well as the other two adjusted models. In contrast, the high-vegetable dietary pattern shows a significant protective effect on IBD in the third and fourth quartiles in all the models. Thus, a high-vegetable dietary pattern may be protective against the risk of IBD, while a high-protein dietary pattern is associated with an increased risk of IBD among a group of the Jordanian population.     

Differences in Dietary Patterns of Adolescent Patients with IBD

Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC). The prevalence of both in pediatric populations has been constantly increasing. This study aimed to analyze the diet of adolescent patients with IBD in comparison to healthy controls and the current dietary standards for the Polish population to further their optimal supplementation regimen. The study group consisted of 53 patients (21 girls and 32 boys) with IBD (CD: n = 27; UC: n = 26) at a mean age of 15.4 ± 2.4 and 14.7 ± 2.2, years for girls and boys, respectively. The control group (CG) consisted of 20 patients, and 72 h of recall diaries on nutrition were collected. The nutritional data were analyzed in the Dieta 6D dietary program. When compared to Polish dietary standards, the largest differences girls with IBD and boys with IBD were found for the intake of energy (61.9 and 71.9%), iodine (61.9 and 62.6%), folates (76.2 and 87.5%), vitamin D (100 and 96.9%), potassium (61.9 and 59.4%), and calcium (85.7 and 93.8%). The overconsumption of saturated fatty acids (SFA) (61.9 and 56.3%) and sodium (76.2 and 90.6%) in girls and boys, respectively, was noted. In relation to girls with CG, girls with IBD showed a significantly higher intake of energy (1751. 3 vs. 1558.6 p = 0.0224), total protein (71.3 vs. 56.2 p = 0.0217), animal protein (47.8 vs. 34.5 p = 0.0183), total carbohydrates (237.3 vs. 196.1 p = 0.0442), and assimilable carbohydrates (219.8 vs. 180.5 p = 0.7921). Boys in the CG consumed significantly more calcium (851.8 vs. 432 p = 0.0006), phosphorus (1024.3 vs. 1357.5 p = 0.0431), lactose (11.6 vs. 6.1 p = 0.0016), and riboflavin (1.7 vs. 1.3 p = 0.0123) compared to boys with IBD. Dietician care should therefore be mandatorily provided alongside outpatient care. Based on our results, we suggest that supplementation with the selected components be considered.     

Role of diet and nutrition in inflammatory bowel disease

Inflammatory bowel diseases (IBDs) are closely linked to nutrition. The latest research indicates that diet and nutrition are significantly involved in the etiopathogenesis of the disease, although their specific role throughout its clinical course still remains unclear. This study reviewed how diet and nutrition are associated with IBD development and management. Even though specific diets have been shown to bring about positive outcomes, there is currently no scientific consensus regarding an appropriate diet that would benefit all IBD patients. We suggest that individualized dietary recommendations are of the greatest importance and that diets should be planned to provide individual IBD patients with specific nutrient requirements while keeping all the clinical aspects of the patients in mind. Further research is clearly necessary to investigate nutritional factors involved in IBD development and, especially, to evaluate the applications of the diets during the course of the disease.     

The Effects of Fatty Acids on Inflammatory Bowel Disease: A Two-Sample Mendelian Randomization Study

Inflammatory Bowel Disease (IBD) is a severe relapsing inflammation of the gastrointestinal tract. The association between fatty acids (FAs) and IBD is controversial and it remains unclear whether there is a causal relationship between them. Mendelian randomization (MR) analysis was province/state for affiliations from the same country performed to clarify the causality. Eligible single nucleotide polymorphisms were selected as instrumental variables from six Genome-wide association studies, involving 114,999 individuals in UK Biobank. The summary-level data on IBD, including Crohn’s disease (CD) and ulcerative colitis (UC), were obtained from the International Inflammatory Bowel Disease Genetics Consortium with 20,883 and 27,432 individuals involved. The primary inverse variance weighted (IVW) method as well as other supplementary analysis ones were adopted to evaluate the causal relationship between diverse FAs and IBD. The tests for heterogeneity and pleiotropy, and Leave-one-out analysis were adopted to verify the stability of the results. Omega-3 FA was found to have a causal effect on UC instead of CD. For each Standard Deviation increase in Omega-3 FA genetic levels, the risk of ulcerative colitis was found to be reduced by 39.9% by the IVW method (p = 1.766 × 10⁻⁴), by 57.8% by the MR Egger (p = 1.11 × 10⁻²), by 51.5% by the Weighted median estimator (p = 7.706 × 10⁻⁴), by 39% by the Maximum likelihood estimation (p = 3.262 × 10⁻⁴), and by 54.5% by the penalized weighted median estimator (p = 1.628 × 10⁻⁴). No causal relationship was found between other FAs (including total FA, saturated FA, polyunsaturated FA, monounsaturated FA and omega-6 FA) and IBD. The pleiotropic test and Leave-one-out analysis both proved the validity and reliability of these MR analyses. Omega-3 FA was observed to have a protective effect against UC, providing a new perspective on the investigation of the associations between FAs and IBD.     

Immune response to hepatitis B vaccination among people with inflammatory bowel diseases: A systematic review and meta-analysis

IntroductionThe response rate to hepatitis B virus (HBV) vaccination in patients with inflammatory bowel disease (IBD) is low and varies markedly. We performed a systematic review and meta-analysis to determine the response rate to HBV vaccination and identified the factors predictive of an immune response.MethodsWe searched PubMed, Cochrane Library, and Embase databases, and reviewed the titles and abstracts of studies on the efficacy of HBV vaccination in IBD patients performed through July 2016. Anti-HBs levels > 10 IU/L was considered to be an effective immune response. The primary outcome measure was the response rate to HBV vaccination after series completion, and the secondary outcome was identification of factors at baseline predictive of an immune response.ResultsThirteen studies including 1688 patients were eligible for inclusion. Based on a random-effects model, the pooled rate of a response to HBV vaccination among patients with IBD was 61% (95% confidence interval [CI]: 53–69). Young age (mean difference [MD]: −5.7; 95% CI: −8.46, −2.95) and vaccination during disease remission (relative risk [RR]: 1.62; 95% CI: 1.15–2.29) were associated with a positive response to HBV vaccination. In addition, no immunosuppressive therapy was predictive of an immune response compared to immunomodulatory (RR: 1.33; 95% CI: 1.08–1.63) or anti-tumor necrosis factor-α (anti-TNF-α) (RR: 1.57; 95% CI: 1.19–2.08) therapy.ConclusionsBased on this meta-analysis, only three of five IBD patients will show a serological response to HBV vaccination. Vaccination should be performed at the time of IBD diagnosis, during disease remission, or before starting immunosuppressive therapy.     

Current state of dietetic services for inflammatory bowel disease patients in New Zealand: an observational study

Aim

Nutritional therapies for inflammatory bowel disease are increasingly recommended. This study aimed to gain insight from patients, dietitians and gastroenterologists into inflammatory bowel disease dietetic care in New Zealand.

Methods

Mixed-methods surveys were developed and then distributed online to patients with inflammatory bowel disease and dietitians and gastroenterologists that care for patients with inflammatory bowel disease. Quantitative survey data were analysed using nonparametric statistical tests. Qualitative survey data were analysed using thematic analysis.

Results

Responses were received from 406 inflammatory bowel disease patients, 79 dietitians and 40 gastroenterologists. Half of the patients (52%) had seen a dietitian for nutrition advice. Patients more likely to have seen a dietitian were/had: Crohn's disease (p = 0.001), previous bowel surgery (p < 0.001), younger (p < 0.001) or receiving biologic therapy (p = 0.005). Two-thirds (66%) of patients found the dietitian advice at least moderately useful. A common theme from patient comments was that dietitians needed better knowledge of inflammatory bowel disease. Almost all (97%) gastroenterologists reported that their inflammatory bowel disease patients ask about nutrition; 57% reported that there were inadequate dietitians to meet patient needs. Over 50% of dietitians saw inflammatory bowel disease patients infrequently and 39% were not confident that their knowledge of the nutritional management of inflammatory bowel disease was current. Dietitians desired greater links with the inflammatory bowel disease multidisciplinary team.

Conclusion

Current inflammatory bowel disease dietetic services in New Zealand are inadequate. Standardised care, increased resourcing, dietitian training in inflammatory bowel disease, and stronger links with the multidisciplinary team are suggested to improve services.