Antioxidant, Anti-Inflammatory, and Microbial-Modulating Activities of Essential Oils: Implications in Colonic Pathophysiology.

Essential oils (EOs) are a complex mixture of hydrophobic and volatile compounds synthesized from aromatic plants, most of them commonly used in the human diet. In recent years, many studies have analyzed their antimicrobial, antioxidant, anti-inflammatory, immunomodulatory and anticancer properties in vitro and on experimentally induced animal models of colitis and colorectal cancer. However, there are still few clinical studies aimed to understand their role in the modulation of the intestinal pathophysiology. Many EOs and some of their molecules have demonstrated their efficacy in inhibiting bacterial, fungi and virus replication and in modulating the inflammatory and oxidative processes that take place in experimental colitis. In addition to this, their antitumor activity against colorectal cancer models makes them extremely interesting compounds for the modulation of the pathophysiology of the large bowel. The characterization of these EOs is made difficult by their complexity and by the different compositions present in the same oil having different geographical origins. This review tries to shift the focus from the EOs to their individual compounds, to expand their possible applications in modulating colon pathophysiology.

Eicosapentaenoic Acid Reduces Fecal Levels of Calprotectin and Prevents Relapse in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: High fecal levels of calprotectin indicate mucosal inflammation and have been shown to predict relapse in patients with ulcerative colitis (UC). Eicosapentaenoic acid (EPA), the major component of n-3 fish oil, has anti-inflammatory properties in patients with chronic inflammatory disorders. We performed a placebo-controlled trial of patients with UC at risk of relapse to determine the ability of the free fatty acid form of EPA (EPA-FFA) to reduce intestinal inflammation, using fecal level of calprotectin as a marker. METHODS: From June 2014 to May 2016, 60 patients with UC with a partial Mayo score < 2 and fecal calprotectin ≥150 µg/g, in stable therapy for at least the 3 previous months, were randomly assigned to groups (1:1) given either EPA-FFA (500 mg, twice daily) or placebo for 6 months. A colonoscopy was performed at baseline. Clinical assessments and measurements of fecal calprotectin were made at baseline, at study months 3 and 6, or the time of clinical relapse. Patients with a relapse of UC underwent a second colonoscopy. The primary end point was a 100-point reduction in fecal levels of calprotectin at 6 months from the baseline value; the secondary end point was maintenance of clinical remission at 6 months. RESULTS: The primary end point was achieved by 19 of 30 patients (63.3%) in the EPA-FFA group vs 4 of 30 patients (13.3%) in the placebo group (odds ratio, 12.0; 95% CI, 3.12-46.24; P < .001). The secondary end point was achieved by 23 of 30 patients (76.7%) in the EPA-FFA group vs 15 of 30 (50%) patients in the placebo group (OR, 3.29; 95% CI, 1.08-9.95; P = .035). No serious adverse events were observed. CONCLUSIONS: In a placebo-controlled trial of 60 patients with UC, we found 6 months' administration of EPA-FFA to reduce fecal levels of calprotectin with no serious adverse events. This agent might be used to induce and maintain symptom-free remission in patients with UC. ClinicalTrials.gov number: NCT02179372.

Dietary geraniol ameliorates intestinal dysbiosis and relieves symptoms in irritable bowel syndrome patients: a pilot study.

BACKGROUND: (Trans)-3,7-Dimethyl-2,6-octadien-1-ol, commonly called geraniol (Ge-OH), is an acyclic monoterpene alcohol with well-known anti-inflammatory and antimicrobial properties. Ge-OH is a non-toxic compound classified as Generally Recognized As Safe (GRAS) by the US Food and Drug Administration and the European Food Security Agency. METHODS: Ge-OH was orally administered at a maximum daily dose of 8 mg kg(- 1) body weight for four weeks in a delayed release formulation capable of reaching the colon. Fecal microbiota and blood cytokines were analyzed before and after Ge-OH treatment, as well as IBS symptomatology by using Visual Analogue Scale (VAS-IBS). RESULTS: The results show that orally administered Ge-OH is a powerful modulator of the intestinal microbial ecosystem, capable of leading to increased relative abundances of Collinsella and especially Faecalibacterium, a well-known health-promoting butyrate producer consistently found to be decreased in IBS patients. Moreover, Ge-OH strongly improved the clinical symptoms of colitis by significantly reducing the score recorded by the VAS-IBS questionnaire. Clinical improvement was associated with a significant reduction in the circulating MIP-1ß, a chemokine found to be increased in several IBS patients. CONCLUSION: Ge-OH could be a powerful component for food supplement targeted to the treatment of IBS patients. TRIAL REGISTRATION: ISRCTN47041881 , retrospectively registered on 19th July 2018.

Can supplementation of phytoestrogens/insoluble fibers help the management of duodenal polyps in familial adenomatous polyposis?

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disorder, and prophylactic colectomy has been shown to decrease the incidence of colorectal cancer (CRC). Duodenal cancer and desmoids are now the leading causes of death in FAP. We evaluate whether 3 months of oral supplementation with a patented blend of phytoestrogens and indigestible insoluble fibers (ADI) help the management of FAP patients with ileal pouch-anal anastomosis (IPAA). In a prospective open label study, we enrolled 15 FAP patients with IPAA and duodenal polyps who underwent upper gastrointestinal endoscopy at baseline and after 3 months of treatment. The primary endpoint was the change in gene expression in polyp mucosa, whereas the secondary endpoint was the reduction in polyp number and size. After 3 months of ADI treatment, all patients showed a reduction in the number and size of duodenal polyps (P = 0.021). Analysis of the expression of CRC promoting/inhibiting genes in duodenal polyps biopsies demonstrated that different CRC-promoting genes (PCNA, MUC1 and COX-2) were significantly downregulated, whereas CRC-inhibiting genes (ER-ß and MUC2) were significantly upregulated after ADI treatment. In conclusion, ADI proved to be safe and effective, and its long-term effects on FAP patients need further investigation. Judging from the results we observed on COX-2 and miR-101 expression, the short-term effects of ADI treatment could be comparable with those obtained using COX-2 inhibitors, with the advantage of being much more tolerable in chronic therapies and void of adverse events.

Loss of miR-101 expression promotes Wnt/ß-catenin signalling pathway activation and malignancy in colon cancer cells.

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in Western countries. Although the aberrant expression of several microRNAs (oncomiRs) is associated with CRC progression, the molecular mechanisms of this phenomenon are still under investigation. Here we show that miR-101 expression is differentially impaired in CRC specimens, depending on tumour grade. miR-101 re-expression suppresses cell growth in 3D, hypoxic survival and invasive potential in CRC cells showing low levels of miR-101. Additionally, we provide molecular evidence of a bidirectional regulatory mechanism between miR-101 expression and important CRC pro-malignant features, such as inflammation, activation of the Wnt/ß-catenin signalling pathway and epithelial-mesenchymal transition (EMT). We then propose that up-regulated miR-101 may function as a tumour suppressor in CRC and that its pharmacological restoration might hamper the aggressive behaviour of CRC in vivo. MiR-101 expression may also represent a cancer biomarker for CRC diagnosis and prognosis.

Attachment and quality of life in patients with inflammatory bowel disease.

PURPOSE: Inflammatory bowel diseases (IBD) are chronic disorders affecting psychological well-being, quality of life (QOL), social interactions, and close interpersonal relationships of patients affected. The attachment theory provides a theoretical framework to evaluate the quality of close interpersonal relationships in the context of chronic disorders. The aims of this study were to compare the attachment dimensions between IBD patients and healthy controls and to evaluate the impact of these dimensions on QOL in IBD patients. METHODS: One hundred three consecutive IBD outpatients (70 with Crohn's disease and 33 with ulcerative colitis) were recruited in the IBD Unit of the University of Bologna. They were clinically evaluated and filled out the questionnaire Short Form health survey-36 (SF-36), assessing QOL, and the attachment style questionnaire (ASQ), assessing attachment dimensions. One hundred three matched healthy subjects filled out the same questionnaires and represented the control group. RESULTS: IBD patients exhibited worst scores in the QOL measures (both physical and mental health) and in the attachment dimensions Relationships as secondary and Preoccupation with relationships. In IBD, the significant predictors of physical health were disease activity and disease type, while the significant predictors of mental health were disease activity and type, surgery, and the attachment dimensions Confidence and Preoccupation with relationships. CONCLUSIONS: Compared to controls, in IBD patients, the close interpersonal relationships are characterized by attachment insecurity that, in turn, is a significant predictor of QOL. These findings suggest plausible insights for psychological interventions in IBD patients with deterioration in QOL.

Functional magnetic resonance imaging study reveals differences in the habituation to psychological stress in patients with Crohn's disease versus healthy controls.

In patients with Crohn's disease (CD) stress is believed to increase the incidence of disease relapse. The brain processes stressful stimuli and triggers the stress-evoked responses. Habituation to stress is an adaptive process that allows minimizing these responses. We hypothesized inadequate habituation to stress in CD patients. The aim of this study was to compare the neural habituation between CD patients and controls. Twenty CD patients and eighteen controls underwent a functional magnetic resonance imaging while performing two repeated runs of a stress-evoking task. The task elicited different neural activity between the groups across runs in (1) amygdala, hippocampus, (2) insula, putamen (3) cerebellar regions, suggesting altered habituation to stress in patients. These structures regulate the neuroendocrine and autonomic stress-evoked responses that control the proinflammatory responses. The inadequate habituation to stress that we found in patients could play a role in the relationship between stress and inflammatory exacerbations in CD.

Drug delivery by polymeric micelles: an in vitro and in vivo study to deliver lipophilic substances to colonocytes and selectively target inflamed colon.

Colitis is the term used for chronic inflammatory bowel diseases at substantially increased risk of developing a form of colorectal cancer (CRC) known as colitis-associated cancer. In our study we synthesized core-shell polymeric micelles obtained by self-assembly of block copolymers for high efficiency delivery of anti-inflammatory and anti-cancer compounds to colonocytes and colon mucosa. We achieved an efficient intracellular delivery of these hydrophobic compounds (prednisone, retinoic acid and doxorubicin) to cultured colonocytes without cellular toxicity. The efficacy of retinoic acid and doxorubicin administration was significantly increased using these nanosized carriers. Moreover, these polymeric micelles have been shown to overcome the multidrug resistance efflux mechanism effectively delivering doxorubicin to multidrug-resistant colon cancer cells. These nanocarriers are also suitable for selective in vivo delivery of lipophilic drugs by enema administration to the inflamed colon tissue, specifically targeting the inflamed mucosa. FROM THE CLINICAL EDITOR: This team of investigators studied polymeric micelles as highly efficient drug delivery systems enabling intracellular delivery of hydrophobic compounds (prednisone, retinoic acid, and doxorubicin) to cultured colonocytes without cellular toxicity, also demonstrating beneficial in vivo effects.

Parental bonding and inflammatory bowel disease.

BACKGROUND: Previous studies have shown a relationship between inflammatory bowel disease (IBD) and psychological stress. Adverse parenting is recognized as an important risk factor for the development of psychiatric disorders in adulthood. OBJECTIVE: The authors sought to further investigate this relationship by clarifying aspects of the bonding relationship in IBD patients and control subjects. METHOD: A group of 307 patients with IBD and a group of 307 healthy subjects filled out the questionnaire Parental Bonding Instrument. RESULTS: Patients with IBD perceived their parents' behaviors as characterized by low care and paternal overprotection; the category Optimal Parenting differs highly in the two samples. CONCLUSION: This study demonstrated an association between inadequate parenting and a chronic physical illness. These findings are consistent with a growing literature that links early parental experience to chronic illness.

Adult attachment and early parental experiences in patients with Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease. The relationship of attachment to the illness is considered to be bidirectional. OBJECTIVE: The authors investigated aspects of this bidirectional relationship. METHOD: A group of 102 patients with CD and 306 healthy subjects filled out the Attachment Style Questionnaire and the Parental Bonding Instrument. RESULTS: Patients with CD exhibit a predominantly insecure attachment and perceived their parents' behaviors as characterized by low maternal care and high paternal overprotection. DISCUSSION: The evaluation of attachment style and early parental experiences in patients with CD may shed light on the bidirectional relationship between attachment and illness. These findings may confirm the bidirectional relationship between insecure attachment and chronic illness.

Refractory Complex Crohn's Perianal Fistulas: A Role for Autologous Microfragmented Adipose Tissue Injection.

BACKGROUND: Complex perianal fistulas represent one of the most challenging manifestations of Crohn's disease. Combined surgical and medical therapy with biologic drugs today represent the first-line treatment option, but its efficacy does not exceed 60%. Recently, new therapeutic approaches, such as the use of mesenchymal stromal cells, have shown promising results. The adipose tissue is an abundant and easy to access source. The effectiveness, safety, and feasibility of local injections of microfragmented adipose tissue in patients with refractory complex fistulizing perianal Crohn's disease (PCD) were evaluated. METHODS: Fifteen patients with persistent complex fistulizing PCD after biosurgical approach and subsequent surgical "rescue" repair were treated in S. Orsola-Malpighi Hospital with a single-local administration of microfragmented adipose tissue prepared using a minimal manipulation technique (Lipogems) in a closed system. Clinical outcomes were determined at 24-week follow-ups assessing success rate, defined as combined clinical and radiological remission. RESULTS: Upon clinical examination at 24 weeks, 10 patients had combined remission (clinical and radiographic), 4 patients showed improvements, and 1 patient failed. The results were confirmed in all patients by pelvic MRI. No relevant postoperative complications nor adverse events were reported. CONCLUSION: These results suggest that the local injection of autologous microfragmented adipose tissue is a safe and promising "rescue therapy" for patients with multiresistant complex fistulizing PCD. This approach might be proposed as routine because it is affordable, is minimally invasive, has no risk of sphincteric damage, and can be carried out in a day-surgery setting.

Attachment and Mentalizing Abilities in Patients with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel diseases (IBD) are associated with stress, poor quality of life, and attachment insecurity. Mentalization is the human ability to perceive and reason about feelings and psychological dispositions of one's self and others. The chronic disorders are believed to affect patients' mentalizing abilities and to determine a shift towards attachment insecurity in patients affected. In this study, the attachment dimensions and mentalization were assessed in IBD patients and healthy controls. Further knowledge about the interplay among IBD, mentalization, and attachment might shed more light into the psychopathological mechanisms leading to insecurity and vulnerability to stress in IBD. METHODS: A group of 96 IBD patients and 102 healthy controls completed the attachment style questionnaire (ASQ), the reflective functioning questionnaire (RFQ), and the Eyes test, a performance-based measure of mentalization. RESULTS: Compared to controls, IBD patients have shown more pronounced attachment anxiety and lower scores in the Eyes test. Disease activity was negatively correlated with the Eyes test scores. CONCLUSION: These findings have suggested a plausible impact of IBD on mentalization abilities and have provided new insights into the interplay between IBD, deficits in mentalization, and attachment insecurity. IBD patients are highly vulnerable to disease-related stress that may promote impairments in mentalization. Low mentalization might play a central role in the development of attachment insecurity and emotional disturbances in IBD. The present study's results might open new scenarios for psychodynamic approaches to the treatment of the emotional disturbances in IBD based on attachment and mentalization theory.

The safety of beclomethasone dipropionate in the treatment of ulcerative colitis.

INTRODUCTION: Beclomethasone dipropionate (BDP) is a second-generation corticosteroid that uses novel drug technologies to ensure colonic targeting and potentially reducing systemic corticosteroid concentrations. It is approved for treatment of patients with mild-to-moderate ulcerative colitis (UC) who do not respond to mesalazine. The gut-selective mechanism of action has the potential to improve the safety profile of BDP compared with other conventional corticosteroids. Areas covered: We reviewed the mechanism of action, efficacy, and safety of BDP in the treatment of UC. The positioning of BDP in management algorithms is also discussed. Expert opinion: The highly selective mechanism of action of BDP restricts the steroid-related side effects. BDP is efficacious in the treatment of active UC. Topical formulation is the first choice in distal UC, while oral formulation is used in patients with an extensive involvement of the colon. The rates of adverse events (AE), serious AEs, and steroid-related side-effects are similar to placebo and mesalamine and slightly inferior to traditional corticosteroids.

Mucosa-associated microbiota dysbiosis in colitis associated cancer.

Gut microbiota dysbiosis has been associated with inflammatory bowel diseases (IBD). In colorectal cancer, the gut microbiota has also been recognized as potentially involved in aggravating or favoring the tumor development. However, very little is known on the structure and role of the microbiota in colitis associated cancer (CAC), an important complication of IBD in human. Here we analyzed the bacterial and fungal composition of the mucosa associated microbiota of patients suffering CAC, sporadic cancer (SC) and of healthy subjects (HS) by barcode sequences analysis on the following cohort: 7 CAC patients, 10 SC patients and 10 HS using 16S (MiSeq) and ITS2 (pyrosequencing) sequencing, for bacteria and fungi respectively. Mucosa-associated bacterial microbiota in CAC was significantly different from the ones in SC or in HS, while the fungal showed no differences. Comparison between mucosa-associated microbiota on the tumor site or in normal mucosa near the tumor showed very similar patterns. The global mucosa-associated bacterial microbiota in cancer patients was characterized by a restriction in biodiversity but no change for the fungal community. Compared to SC, CAC was characterized by an increase of Enterobacteriacae family and Sphingomonas genus and a decrease of Fusobacterium and Ruminococcus genus. Our study confirms the alteration of the mucosa-associated bacterial microbiota in IBD and SC. Although the cohort is limited in number, this is the first evidence of the existence of an altered bacterial microbiota in CAC clearly different from the one in SC patients.

Cutaneous manifestations in inflammatory bowel diseases: eight cases of psoriasis induced by anti-tumor-necrosis-factor antibody therapy.

BACKGROUND: Ulcerous rectocolitis and Crohn's disease are the best known forms of inflammatory bowel disease (IBD). Skin manifestations are not uncommon in IBD and may be divided into specific cutaneous signs, aspecific cutaneous signs, and cutaneous signs caused by drugs used for IBD therapy. The specific signs (fistulas, rhagades and ulcers) are the result of the diffusion of the intestinal inflammatory process into the skin. Aspecific cutaneous signs (stomatic aphthosis, erythema nodosum, pyoderma gangrenosum, Sweet's syndrome, vasculitis, bullous diseases) are quite frequently found in those suffering from IBD, but also in apparently healthy subjects, and may sometimes be the first sign of the intestinal disease. Cutaneous manifestations due to drugs vary in clinical aspect and are the direct consequence of the therapies adopted, which in IBD patients can be quite numerous: steroids, immunosuppressants, 5-aminosalicylic acid, biological agents, antibiotics. OBJECTIVE AND METHODS: Due to the frequent finding of cutaneous manifestations in patients affected by IBD, a collaboration was set up between the Dermatological Clinic of the University of Bologna and the Center for the Study of IBD of the same university hospital. The aim was to diagnose the cutaneous signs appearing during IBD and to establish their etiopathogenesis in order to assess whether they were the result of epiphenomena of the IBD or side effects of the therapies adopted. RESULTS: The cutaneous manifestations we observed can be divided into three distinct groups: signs that were specific to the basic disease, aspecific signs and finally signs attributable to the drugs used for therapy. Particular attention was given to the aspecific signs and those consequential to therapy. The aspecific cutaneous signs seen in our clinic generally reflect those reported in the literature. The cutaneous manifestations due to drugs were further divided into three groups: rosacea, acneiform dermatitis and psoriasis-like dermatitis. The most notable aspect of our series is the high number of patients presenting psoriasiform-type dermatitides with a generally widespread diffusion. CONCLUSION: We would like to draw attention to the fact that all patients with psoriasis had been undergoing treatment with drugs inhibiting tumor necrosis factor alpha (TNF-alpha) as part of IBD therapy. In all cases, the cutaneous reaction started after the third or fourth infusion of the biological drug. Anti-TNF-alpha agents have also been successfully used to treat psoriasis in the last few years. The reason for this apparently paradoxical effect of the therapy is still unclear.

Prevalence and effectiveness of psychiatric treatments for patients with IBD: A systematic literature review.

OBJECTIVES: Higher prevalence of psychiatric disorders, such as anxiety and depression, has been found in people with Crohn's disease and Ulcerative Colitis compared to the general population. Nowadays, international guidelines advocate psychotherapy and psycho-pharmacological treatments as playing an important role in IBD care. The main goal of this systematic literature review was summarize the evidence on the utilization and effectiveness of treatments for depression and anxiety in persons with IBD. METHODS: A systematic literature review was conducted using three different electronic databases: MEDLINE, PsychINFO, and EMBASE to identify studies reporting the prevalence and efficacy of psycho-pharmacological and psychotherapeutic treatments for IBD. A quality appraisal was conducted using several scales as appropriate for each study design. A narrative synthesis was also performed. RESULTS: Forty-three studies were included. Although a high rate of psychoactive drug use was found in people with IBD, a low proportion of IBD patients have access to psychiatric referral. 1/3 of the studies found that psychotherapy was effective for improving the quality of life, perception of stress, anxiety and depression as well as disease. Antidepressants proved effective in reducing disease activity, gastrointestinal symptoms, anxiety and depression. CONCLUSION: Our results suggest that psychiatric treatment should be implemented in IBD care. However, further studies are needed to confirm the findings of our systematic review.

Real-time elastography for the detection of fibrotic and inflammatory tissue in patients with stricturing Crohn's disease.

PURPOSE: The distinction between active inflammation and fibrosis of the bowel wall is essential for therapeutic decisions in stricturing Crohn's disease. We aimed to assess whether real-time elastography (RTE) with strain ratio measurement could be useful in differentiating fibrotic from inflamed bowel strictures and to evaluate the possible relationship between US techniques and the histology of the stenotic bowel wall. MATERIALS AND METHODS: Bowel ultrasonography (including RTE, color-Doppler and CEUS examination) was prospectively evaluated in 26 patients with symptomatic stricturing Crohn's disease, before surgery. RTE was adopted to evaluate bowel stiffness: five loops of 20 RTE frames were recorded for each stenotic segment and the mean strain ratio (MSR) was obtained. Histology scoring systems both for inflammation and fibrosis were established for surgical specimens. RESULTS: No significant correlation was found between MSR and fibrosis score (P = 0.877). Color-Doppler score was significantly related to gut wall and submucosal thicknesses (P = 0.006 and P = 0.032, respectively). There was no significant correlation between the number of vessels counted at histology and color-Doppler and CEUS examinations (P = 0.170 and P = 0.302, respectively). CONCLUSION: MSR detection was not able to distinguish fibrotic from inflammatory tissue in our selected population. This result could be influenced by the presence of the superimposed inflammation. Larger cohort of patients, further analysis with shear wave elastography, and validated histopathology classification systems for fibrosis and inflammation are necessary to assess if intestinal fibrosis could be reliably detected on the basis of bowel elastic properties.

Antibiotics and probiotics in treatment of inflammatory bowel disease.

Many experimental and clinical observations suggest that intestinal microflora plays a potential role in the pathogenesis of inflammatory bowel disease (IBD). Manipulation of the luminal content using antibiotics or probiotics represents a potentially effective therapeutic option. The available studies do not support the use of antibiotics in ulcerative colitis (UC). Antibiotics are effective in treating septic complications of Crohn's disease (CD) but their use as a primary therapy is more controversial, although this approach is frequently and successfully adopted in clinical practice. There is evidence that probiotic therapy may be effective in the prevention and treatment of mild to moderate UC. In contrast, a lack of successful study data at present precludes the widespread use of probiotics in the treatment of CD. Both antibiotics and probiotics appear to play a beneficial role in the treatment and prevention of pouchitis and further trials are warranted to fully quantify their clinical efficacy.

Effects of probiotic bacteria on gastrointestinal motility in guinea-pig isolated tissue.

AIM: To evaluate the intestinal motility changes evoked by 8 bacterial strains belonging to Bifidobacterium, Lactobacillus and Streptococcus genera within the probiotic preparation VSL#3. METHODS: Ileum and proximal colon segments isolated from guinea-pigs were used as a study model. Entire cells and cell fractions (cell debris, cell wall fraction, cytoplasmatic fraction, proteinaceous and non-proteinaceous cytoplasmatic components) of VSL#3 strains and, as controls, Escherichia coli, Salmonella aboni and Bacillus licheniformis were tested in this in vitro model. RESULTS: Among the bacterial cell fractions tested, only the cytoplasmatic fraction modified intestinal motility. Lactobacillus strains stimulated the contraction of ileum segment, whereas all probiotic strains tested induced proximal colon relaxation response. The non-proteinaceous cytoplasmatic components were responsible for the colon relaxation. CONCLUSION: The results obtained in this study suggest that the proximal colon relaxation activity showed by the probiotic bacteria could be one of the possible mechanisms of action by which probiotics exert their positive effects in regulating intestinal motility.