The significance of nutritional strategies in patients with inflammatory bowel disease in the context of malnutrition and the development of malnourished obesity.

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, despite the increasing incidence, still do not have a specific etiology. Diet seems to be an important factor, modifying the occurrence of the disease and its course. Diet can affect the symptoms of IBD both directly, e.g., by alleviating diarrhea, bloating and constipation, and indirectly by shaping the microbiota. Bacterial metabolites produced under the influence of supplied nutrients may contribute to the modulation of pro- and anti-inflammatory pathways, depending on the diet used. So far, IBD has been associated with weight loss and malnutrition. In recent years, a trend of sarcopenic obesity with concomitant malnutrition has been observed. The new phenomenon is called malnubesity. This work aims to review the most commonly used diets in IBD in order to evaluate them in terms of alleviating ailments, but also maintaining proper nutritional status and lack of obesity. Low-fiber, low FODMAPs, Mediterranean diet and Crohn's Disease Exclusion Diet diet were considered. We assume that diet is modifiable factor that is related to nutritional status and healthy body weight. In addition, the current knowledge on the relationship between nutrition strategies, obesity and IBD will be demonstrated.

The Importance of Nutritional Aspects in the Assessment of Inflammation and Intestinal Barrier in Patients with Inflammatory Bowel Disease.

Intestinal inflammation in inflammatory bowel disease (IBD) is closely linked to nutrition. This study aimed to evaluate associations between nutritional, inflammatory, and intestinal barrier parameters in patients with IBD. We assessed nutritional status, fecal short-chain fatty acid profile, serum cytokine levels, and mRNA expression of enzymes and tight junction proteins in intestinal biopsies obtained from 35 patients, including 11 patients with inactive IBD, 18 patients with active IBD, and six controls. Patients with active IBD were characterized by hypoalbuminemia, fluctuations in body weight, and restriction of fiber-containing foods. In addition, they had significantly reduced levels of isovaleric acid and tended to have lower levels of butyric, acetic, and propionic acids. Patients with active IBD had higher mRNA expression of peroxisome proliferator-activated receptor γ and inducible nitric oxide synthase, and lower mRNA expression of claudin-2 and zonula occludens-1, compared with patients with inactive IBD. Moreover, patients with a body mass index (BMI) of ≥25 kg/m2 had higher median tumor necrosis factor-α levels that those with a lower BMI. We comprehensively evaluated inflammatory parameters in relation to IBD activity and nutritional status. The discrepancies between proinflammatory and anti-inflammatory parameters depending on IBD activity may be related to nutritional factors, including diet and abnormal body weight.

Application of the Clustering Technique to Multiple Nutritional Factors Related to Inflammation and Disease Progression in Patients with Inflammatory Bowel Disease.

Diet and nutritional status affect intestinal inflammation in patients with inflammatory bowel disease (IBD). The aim of this study was to use a cluster analysis to assess structural similarity between different groups of parameters including short-chain fatty acid (SCFA) levels in stool as well as hematological and inflammatory parameters (such as serum C-reactive protein (CRP) and proinflammatory and anti-inflammatory cytokines). We also assessed similarity between IBD patients in terms of various biochemical features of disease activity and nutritional status. A total of 48 participants were enrolled, including 36 patients with IBD and 12 controls. We identified four main meaningful clusters of parameters. The first cluster included all SCFAs with strong mutual correlations. The second cluster contained red blood cell parameters and albumin levels. The third cluster included proinflammatory parameters such as tumor necrosis factor-α, CRP, platelets, and phosphoric, succinic, and lactic acids. The final cluster revealed an association between zonulin and interleukins IL-10, IL-17, and IL-22. Moreover, we observed an inverse correlation between IL-6 and body mass index. Our findings suggest a link between nutritional status, diet, and inflammatory parameters in patients with IBD, which contribute to a better adjustment of the nutritional treatment.

Association between fecal levels of Short-Chain Fatty Acids and serum Pro- and Anti-Inflammatory Cytokines in patients with Inflammatory Bowel Disease.

INTRODUCTION: Inflammatory bowel disease (IBD) represents a group of chronic inflammatory disorders characterized by dysbiosis and altered short-chain fatty acid (SCFA) level. The association between individual SCFA levels and cytokine levels is unknown. OBJECTIVES: We aimed to determine the fecal SCFA levels in patients with IBD in relation to disease severity and the serum levels of pro- and anti-inflammatory cytokines. PATIENTS AND METHODS: The study included 61 patients with IBD (inactive, 22; active, 39) and 16 controls. Fecal levels of organic acids (acetic, lactic, propionic, butyric, isovaleric, isobutyric, and valeric), serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), IL-17, and IL-22, complete blood count and C-reactive protein (CRP) were measured. RESULTS: Patients with active IBD had reduced butyric, acetic, valeric, and isovaleric acid levels and elevated lactic acid levels in stool. Hemoglobin levels were positively correlated with the levels of acetic and butyric acids (R = 0.266 and R = 0.346, respectively; P <0.05). In addition, CRP levels were inversely correlated with butyric acid levels (R = -0.573; P <0.05). Higher serum TNF-α levels were observed in patients with active IBD compared with controls (6.64 pg/ml vs 2.05 pg/ml, P <0.05). No relationship was noted between the SCFA profile and cytokine levels. CONCLUSIONS: The study showed that determination of SCFA levels can be used to evaluate the activity of IBD. The relationship between individual SCFA and cytokine levels seems to be complex and requires further studies.

Association between Fecal Short-Chain Fatty Acid Levels, Diet, and Body Mass Index in Patients with Inflammatory Bowel Disease.

Disturbances in the production of bacterial metabolites in the intestine have been reported in diseases associated with dysbiosis, such as inflammatory bowel diseases (IBDs) that include two conditions: Crohn disease (CD) and ulcerative colitis (UC). Short-chain fatty acids (SCFAs) are the main dietary-fiber-derived bacterial metabolites associated with the course of intestinal inflammation. In this study, we assessed the relationship between body mass index (BMI), the type of diet used, and changes in fecal SCFA levels in patients with IBD. We performed nutritional assessments using a nutritional questionnaire and determined fecal SCFA levels in 43 patients with UC, 18 patients with CD, and 16 controls. Our results revealed that subjects with a BMI > 24.99 kg/m2 had higher levels of isobutyric acid, whereas those with a BMI < 18.5 kg/m2 had lower level of butyric, isovaleric, and propionic acids. Furthermore, we observed higher levels of valeric acid in controls than in IBD patients. We did not reveal a relationship between a specific SCFA and the type of diet, but eating habits appear to be related to the observed changes in the SCFA profile depending on BMI. In conclusion, we demonstrated that BMI is associated with SCFA levels in patients with IBD.

Fecal Levels of Lactic, Succinic and Short-Chain Fatty Acids in Patients with Ulcerative Colitis and Crohn Disease: A Pilot Study.

Intestinal dysbiosis plays a crucial role in the development of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). The importance of bacterial metabolites, such as short-chain fatty acids (SCFAs), succinic and lactic acids, as well as environmental factors that affect their production in the course of IBD, remains unclear. The aim of this study was to evaluate a profile of organic acids in the stool of CD and UC patients with different disease activity. We assessed a correlation between used medications, patient's diet, and SCFA levels. A total of 35 adult patients were included in the study. We did not observe significant differences in the levels of organic acids between the CD and UC groups, irrespective of disease activity, and a control group. However, propionic acid levels were higher in IBD patients who received trimebutine vs. those who did not (p = 0.031). Higher isobutyric acid levels were observed in patients treated with biological drugs compared with those without such treatment (p = 0.014). No significant correlations were found between organic acid levels and the frequency of dietary fiber consumption. Our results reveal a new link between medication use and organic acid levels in patients with IBD.

Serum levels of selected micronutrients in patients with inflammatory bowel disease in clinical remission.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) can experience micronutrient deficiency regardless of disease activity and extent. OBJECTIVES: We aimed to evaluate serum concentrations of selected trace elements in adult patients with IBD in clinical remission with involvement limited to the colon who received immunosuppressive treatment. PATIENTS AND METHODS: We enrolled 32 patients with IBD (mean [SD] age, 41 [15.2] years) and 30 healthy controls (mean [SD] age, 39.1 [11.8] years). Serum selenium, iron, copper, and zinc levels as well as complete blood count were measured in both groups. RESULTS: Patients with IBD had lower zinc concentrations than controls (mean [SD], 0.76 [0.13] mg/l vs 0.83 [0.13] mg/l; P = 0.047). No differences were observed for selenium (mean [SD], 0.90 [0.24] µmol/l vs 0.93 [0.19] µmol/l) and copper levels (mean [SD], 1.03 [0.27] mg/l vs 0.97 [0.22] mg/l). Compared with controls, patients with IBD had lower red blood cell count (mean [SD], 4.4 [0.6] 106/µl vs 4.7 [0.4] 106/µl; P = 0.03), hemoglobin (mean [SD], 12.7 [2.2] g/dl vs 14.3 [0.8] g/dl; P = 0.001), and iron levels (mean [SD], 14.2 [9.4] µmol/l vs 23.4 [2.7] µmol/l; P = 0.0001). Patients with IBD showed a positive correlation between selenium and iron (R = 0.499; P = 0.004) as well as selenium and hemoglobin levels (R = 0.579; P = 0.001). CONCLUSIONS: Patients with IBD, despite maintaining clinical remission, should undergo systematic laboratory test for anemia or micronutrient deficiencies.

Effect of long-term proton pump inhibitor therapy on complete blood count parameters and selected trace elements: a pilot study.

INTRODUCTION: Proton pump inhibitors (PPIs) are widely prescribed for several gastrointestinal conditions, often as long­term therapy. The effects of term PPI use have not been fully elucidated. OBJECTIVES: We aimed to determine the association between long­term PPI use and complete blood count parameters, particularly red blood cell (RBC) count, white blood cell (WBC) count, and hemoglobin concentrations, as well as serum levels of selected micronutrients such as selenium (Se), iron (Fe), copper (Cu), and zinc (Zn). PATIENTS AND METHODS: We enrolled 37 patients on long­ term PPI therapy (mean [SD] age, 57.1 [15.4] years) and 30 healthy controls (mean [SD] age, 39.3 [11.8] years). In each group, complete blood count, and serum Fe levels were performed, and serum Cu, Zn, and Se levels were measured using atomic absorption spectrometry. RESULTS: Red blood cell and WBC counts were lower in the PPI group compared with controls (mean [SD], 4.24 [0.55] ×106/µl vs 4.7 [0.4] ×106/µl; P <0.001 and 6.13 [1.44] ×103/µl vs 7.3 [1.28] ×103/µl; P <0.001, respectively). Hemoglobin and serum Fe concentrations were also lower in the PPI group (mean [SD], 12.5 [1.8] g /dl vs 14.3 [0.8] g /dl; P <0.001 and 16.3 [5.4] µmol/l vs 23.4 [2.7] µmol/l; P <0.001, respectively). Serum Zn and Cu concentrations were higher in PPI users than in controls. CONCLUSIONS: Long­term PPI therapy may reduce RBC and WBC counts as well as hemoglobin levels, leading to iron deficiency. It may also aff ect concentrations of some micronutrients, although the underlying mechanism of this association is not fully clear.

Intestinal parameters of oxidative imbalance in celiac adults with extraintestinal manifestations.

AIM: To evaluate selected intestinal parameters of oxidative stress, and antioxidant capacity in adult celiac disease patients with extraintestinal manifestations. METHODS: The study involved 85 adult patients divided into the following subgroups: (1) patients with newly diagnosed celiac disease (CD) (n = 7); (2) celiac patients not adhering to a gluten-free diet (GFD) (n = 22); (3) patients with CD on the GFD (n = 31); and (4) patients with functional disorders of the gastrointestinal tract, serving as controls (n = 25). Celiac patients presented with non-classic symptoms or extraintestinal manifestations. Standard blood tests including serum antioxidant levels (uric acid, bilirubin, and vitamin D), celiac antibody levels, and histopathological status of duodenal biopsy specimens have been determined. The expression of mRNA for tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), interleukin 10 (IL-10), superoxide dismutase (SOD), heat-shock protein 70 (HSP-70), hypoxia-inducible factor 1 (HIF-1α), and BAX in the duodenal mucosa of patients was analyzed by reverse transcriptase-polymerase chain reaction. RESULTS: The mean plasma uric acid level in patients with active CD (newly diagnosed and nonadherent patients) and treated celiac patients was significantly higher than in controls (260.17 ± 53.65 vs 190.8 ± 22.98, P < 0.001, and 261.7 ± 51.79 vs 190.8 ± 22.98, P < 0.001, respectively). The mean bilirubin concentration in active and treated celiac patients was significantly lower than in controls (8.23 ± 5.04 vs 10.48 ± 4.08, P < 0.05 and 8.06 ± 3.31 vs 10.48 ± 4.08, P < 0.05, respectively). The mean plasma vitamin D level was significantly lower in active celiac patients than in treated celiac patients and controls (19.37 ± 9.03 vs 25.15 ± 11.2, P < 0.05 and 19.37 ± 9.03 vs 29.67 ± 5.12, P < 0.001, respectively). The expression of TNF-α, IL-10, and HSP-70 mRNAs was significantly elevated in the celiac groups regardless of the diet when compared with controls. Patients on the GFD presented a significantly lower mRNA expression of TNF-α and IL-10 than in newly diagnosed and nonadherent patients (P < 0.05). The expression of SOD mRNA was significantly elevated in celiac patients compared with controls (P < 0.05), with a significant difference between treated and untreated patients (P < 0.05). The expression of HIF-1α mRNA and BAX mRNA was significantly higher in patients with active CD compared with controls and patients on GFD, while no difference was observed between the latter two groups. CONCLUSION: Increased intestinal expression of HSP-70 despite GFD indicates that GFD only partially reduced oxidative stress. CD patients exhibited an oxidative imbalance and inflammatory response despite GFD. Uric acid may act as an important antioxidant in CD.

Alterations in serum levels of selected markers of oxidative imbalance in adult celiac patients with extraintestinal manifestations: a pilot study.

INTRODUCTION    Oxidative stress is considered to be one of the mechanisms responsible for gluten toxicity, but its role in celiac disease (CD) remains unclear. OBJECTIVES    The aim of the study was to evaluate oxidative imbalance in the pathomechanism of CD by determining the concentrations of nitric oxide (NO) and selected antioxidant parameters. PATIENTS AND METHODS    The study involved 197 adult patients: 53 patients with untreated active CD, 92 celiac patients on gluten­free diet (GFD), and 52 controls. The serum levels of antioxidants (uric acid, bilirubin, ferritin, albumin), celiac antibodies, NO, glutathione peroxidase 3 (GPx3), and vitamin E were measured. A histopathological study of duodenal biopsy was performed. RESULTS    Celiac patients had higher uric acid concentrations than controls (P <0.001). NO levels were higher in patients with active CD than in controls (P <0.01) and were correlated with the degree of mucosal damage (r2 = 0.04; P = 0.01). Vitamin E levels were decreased in celiac patients (P <0.01), and GPx3 activity was reduced in patients with active CD compared with controls (P <0.001). CONCLUSIONS    Oxidative imbalance may be involved in the pathomechanism of CD in adults. GFD only partially reduces oxidative stress. Serum NO levels seem to be a marker of the effectiveness of treatment. Uric acid may act as an antioxidant in CD.

Ferric reducing ability of plasma and assessment of selected plasma antioxidants in adults with celiac disease.

INTRODUCTION: Oxidative stress with an excessive free radical production and a reduction in the activity of protective antioxidants is considered as one of the mechanisms responsible for gluten toxicity. However, its role in celiac disease (CD) is unclear. OBJECTIVES: Evaluation of plasma nonenzymatic antioxidant capacity in patients with CD (both untreated patients and those receiving gluten-free diet [GFD]) by measuring the ferric reducing ability of plasma (FRAP) as well as assessing selected plasma antioxidants. PATIENTS AND METHODS: The study included 169 adult patients: 48 patients with untreated active CD, 72 patients with CD on a GFD, and 49 healthy controls. In each group, we measured the serum levels of selected antioxidants (uric acid, bilirubin, albumin, and vitamin E) and used the FRAP assay to assess the total antioxidant capacity (TAC) of plasma. In each patient, serological and histopathological activity of CD was also evaluated. RESULTS: There were no significant differences in the TAC of plasma measured with the FRAP assay between the study groups. Patients with CD had higher uric acid levels compared with controls (p <0.001), while bilirubin levels were lower in patients with active disease than in controls (p <0.05). Serum vitamin E levels were lower in all patients with CD compared with controls (p <0.01). CONCLUSIONS: The FRAP assay is not the method of choice for assessing the TAC of plasma in patients with CD. Owing to high serum uric acid levels, the FRAP assay results in these patients may be overestimated despite the reduced levels of other plasma antioxidants.

Concentrations of antiganglioside M1 antibodies, neuron-specific enolase, and interleukin 10 as potential markers of autonomic nervous system impairment in celiac disease.

INTRODUCTION Celiac disease (CD) is an immune-mediated enteropathy related to permanent gluten intolerance, characterized by gastrointestinal symptoms as well as nongastrointestinal symptoms, including neurologic ones. The presence of neuron-specific enolase (NSE), interleukin 10 (IL-10), and antiganglioside M1 (anti-GM1) antibodies has been demonstrated for neurologic conditions as well as immune disorders with neurologic manifestations. OBJECTIVES The aim of the study was to determine the concentrations of IL-10, NSE, and anti-GM1 antibodies in the course of CD and their correlation with changes in electrogastrography (EGG) and with heart rate variability (HRV). PATIENTS AND METHODS The study included 68 participants: 34 patients with CD and 34 healthy individuals. We assessed the concentrations of IL-10 and NSE as well as the presence of anti-GM1 antibodies in serum. We investigated correlations between the concentrations of IL-10, NSE, and anti-GM1 antibodies and the results of EGG and HRV. RESULTS Patients with CD had a higher level of anti-GM1 antibodies than controls (1.38 ng/ml [0.98-2.03 ng/ml] vs 0.81 ng/ml [0.35-1.15 ng/ml]). Median IL-10 concentrations in patients with CD differed significantly from those in controls (7 pg/ml [4.33-11.48 pg/ml] vs 4.27 pg/ml [2.44-7 pg/ml]; P = 0.010). In HRV analysis, a positive correlation between IL-10 concentrations and very low frequency spectrum was observed (r = 0.63; P = 0.003). There was no correlation between the concentrations of IL-10, NSE, or anti-GM1 antibodies and EGG parameters. CONCLUSIONS Chronic inflammation in the course of CD may lead to autonomic nervous system impairment and development of neurologic disorders. Therefore, anti-GM1 antibodies and IL-10 may be considered as markers of nervous system impairment in the course of CD.

[Antibodies against alfa-enolase as an indication of inflammatory process in patients with celiac disease--preliminary results]. / Przeciwciala przeciw alfa enolazie, jako wskaznik stanu zapalnego u chorych na celiakie-doniesienie wstepne.

INTRODUCTION: Celiac disease (CD) is an autoimmunological gluten sensitive enteropathy occuring to genetically predisposed individuals. Active CD is accompanied by presence of multiple antibodies. Anti alpha enolase antibodies were reported in several autoimmunological disorders like rheumatoid arthritis, primary sclerosing cholangitis. Data about its presence and role in CD is avaricious. AIM: The aim of this study was to determine presence of anti alpha enolase antibodies in CD, correlation with gluten exposure, presence of anti tranglutaminase antibodies and Marsh scale. METHODS: Sera from 31 patients with CD (21 females, 10 males) and 6 healthy subjects were collected. Evaluation of CD activity and adherence to gluten free diet were obtained by serology tests (presence of endomyslum antibodies and/or anti transglutamineses in IgA or IgG classes) and histological hallmarks. Anti alpha enolase antibodies were identified in sera using ELISA kit. Titres of anti alpha enolase antibodies were identified among patients with newly diagnosed CD, CD patients non adhering to gluten free diet (GFD), adhering to GFD and among healthy subjects. RESULTS: Mean titre of anti alpha enolase antibodies was higher in CD patients (both treated and non treated) in comparison to control group, respectively 1.1 ng/mL, and 0.795 ngl mL. Among CD patients non adhering to gluten free diet mean titre was 1.4 ng/mL. CONCLUSIONS: Higher anti alpha enolase antibodies titres in non treated CD suggest usefulness of its measurement. These antibodies might be a novel marker of chronic inflammation among CD patients non adhering to GFD.

[Endoscopic and histopathological findings of the upper gastrointestinal tract in patients with functional and organic dyspepsia]. / Zmiany endoskopowe i histopatologiczne górnego odcinka przewodu pokarmowego u chorych z dyspepsja organiczna i czynnosciowa.

INTRODUCTION: Endoscopic examination of the upper gastrointestinal tract (upper GI) with macroscopic and histopathological evaluation provides essential tool to differentiate the organic and functional causes of dyspepsia. The distinction, however, is often smooth and not fully defined. The aim of this study was to assess the frequency and type of the macroscopic and histopathological changes in the upper GI endoscopy in patients with symptoms of dyspepsia. MATERIAL AND METHODS: A retrospective study was performed on 212 patients with dyspepsia, at the age of 18-84 years, including 60 patients to 45 years of age (group I) and 152 patients older than 45 (group II) who underwent gastroscopy. The severity of esophagitis was classified according to the Los Angeles Classification and gastritis according the updated Sydney system. Biopsy specimens were taken from the gastric and duodenum for histopathological examination. The presence of H. pylori infection has been established on the basis of histopathological examination and positive rapid urease test. RESULTS: Reflux esophagitis was found in 18 patients (8.5%), slightly more common in people over 45 years of age (group I--5%, group II--9.2%). The mild forms of esophagitis occurred most frequently. A more advanced form of inflammation and Barrett's esophagus was found only in patients over 45 years of age. Normal gastric and duodenal mucosa was revealed in 30% of patients in group I and 9.2% in group II. The most common endoscopic lesion was gastritis, mostly erythematous-exudative and less often atrophic. The presence of H. pylori infection was varied in the different types of inflammation. H. pylori infection occurred most frequently in the case of erosive and follicular gastropathy. The most common location of H. pylori infec- frequent in older patients. Peptic ulcer was found in 4.7% of patients (group I--5%, group II--4.6%). In one patient (61 years old) stomach cancer was diagnosed and in one patient (<45 years old) Crohn's disease of the upper GI was diagnosed. The majority of patients had normal duodenal mucosa. In 3.3% of patients (group I--8.3%, group II--1.3%), who had not previously diagnosed celiac disease, histopathological changes typical of celiac disease has been shown. In all patients, in whom biopsy specimens were taken from normal duodenal mucosa (14% of patients), histopathological examination revealed the presence of non-specific inflammation, regardless of the coexistence of H. pylori infection. CONCLUSION: Regardless of the severity of lesions of the upper GI endoscopy in patients with dyspepsia, it is advisable to take biopsy from the gastric and duodenal mucosa, which allows for an individualized management of these patients. Celiac disease should be considered in the diagnosis of the causes of dyspepsia. Further studies of microscopic duodenitis in patients with dyspepsia are needed.