Publications by authors named "Agata Mulak"

42 Publications

Is Fecal Calprotectin an Applicable Biomarker of Gut Immune System Activation in Chronic Inflammatory Demyelinating Polyneuropathy? - A Pilot Study.

Front Hum Neurosci 2021 12;15:733070. Epub 2021 Nov 12.

Department of Neurology, Wrocław Medical University, Wrocław, Poland.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a complex autoimmune disease caused by dysregulated response to not fully recognized antigens. Some association between CIDP and inflammatory bowel disease (IBD) has been reported, but the exact pathophysiological links of these disorders are not well understood. To evaluate fecal calprotectin as a biomarker of gut inflammation in CIDP patients without IBD. Fifteen patients with CIDP and 15 healthy controls were included in the study. The CIDP diagnosis was based on the EFNS/PNS criteria. The occurrence of bowel symptoms was assessed based on a questionnaire. The quantitative evaluation of fecal calprotectin level was performed by the ELISA test. The fecal calprotectin level (μg/g) expressed as median along with the lower and upper quartiles [25Q-75Q] was significantly higher in CIDP patients compared to the controls: 26.6 [17.5-109.0] vs 15.6 [7.1-24.1], = 0.0066. Abnormal fecal calprotectin level (>50 μg/g) was found in 33% of all CIDP patients and in none of the control subjects. The patients with abnormal fecal calprotectin level did not differ from the rest of the study group regarding the neurological status. The most common bowel symptoms reported by CIDP patients included constipation (33%), feeling of incomplete evacuation (33%), bloating (27%), and alternating bowel movement pattern (27%). In one-third of CIDP patients the signs of gut immune system activation have been observed. This finding may be associated with CIDP pathogenesis and induction of autoimmune response as well as concomitant dysautonomia with gastrointestinal symptoms.
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http://dx.doi.org/10.3389/fnhum.2021.733070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636096PMC
November 2021

Small intestinal bacterial overgrowth in Alzheimer's disease.

J Neural Transm (Vienna) 2022 Jan 19;129(1):75-83. Epub 2021 Nov 19.

Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556, Wrocław, Poland.

The results of animal studies and clinical data support the gut microbiota contribution to the pathogenesis of Alzheimer's disease (AD). The aim of this pilot study was to evaluate the prevalence of small intestinal bacterial overgrowth (SIBO) and fecal markers of intestinal inflammation and permeability in AD patients. The study was conducted in 45 AD patients and 27 controls. Data on comorbidities, pharmacotherapy, and gastrointestinal symptoms were acquired from medical records and a questionnaire. SIBO was evaluated using lactulose hydrogen breath test. Fecal calprotectin and zonulin levels were assessed by ELISA assays. The positive result of SIBO breath test was found in 49% of the AD patients and 22% of the controls (p = 0.025). The comparative analysis between SIBO-positive and SIBO-negative AD patients with respect to the degree of cognitive impairment, comorbidities and used medications did not reveal any statistically significant difference, except for less common heartburn in SIBO-positive AD patients than in SIBO-negative ones (9 vs 35%, p = 0.038). The median fecal calprotectin and zonulin levels in the AD group compared to the control group amounted to 43.1 vs 64.2 µg/g (p = 0.846) and 73.5 vs 49.0 ng/ml (p = 0.177), respectively. In the AD patients there was no association between the presence of SIBO and fecal calprotectin level. Patients with AD are characterized by higher prevalence of SIBO not associated with increased fecal calprotectin level that may be related to anti-inflammatory effect of cholinergic drugs used in the treatment of AD.
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http://dx.doi.org/10.1007/s00702-021-02440-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8738624PMC
January 2022

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

Neurogastroenterol Motil 2021 09;33(9):e14238

Gastroenterology Unit, Departmento of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

Background: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis.

Methods: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements.

Results: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable.

Conclusions And Inferences: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
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http://dx.doi.org/10.1111/nmo.14238DOI Listing
September 2021

Bile Acids as Key Modulators of the Brain-Gut-Microbiota Axis in Alzheimer's Disease.

Authors:
Agata Mulak

J Alzheimers Dis 2021 ;84(2):461-477

Department of Gastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland.

Recently, the concept of the brain-gut-microbiota (BGM) axis disturbances in the pathogenesis of Alzheimer's disease (AD) has been receiving growing attention. At the same time, accumulating data revealing complex interplay between bile acids (BAs), gut microbiota, and host metabolism have shed new light on a potential impact of BAs on the BGM axis. The crosstalk between BAs and gut microbiota is based on reciprocal interactions since microbiota determines BA metabolism, while BAs affect gut microbiota composition. Secondary BAs as microbe-derived neuroactive molecules may affect each of three main routes through which interactions within the BGM axis occur including neural, immune, and neuroendocrine pathways. BAs participate in the regulation of multiple gut-derived molecule release since their receptors are expressed on various cells. The presence of BAs and their receptors in the brain implies a direct effect of BAs on the regulation of neurological functions. Experimental and clinical data confirm that disturbances in BA signaling are present in the course of AD. Disturbed ratio of primary to secondary BAs as well as alterations in BA concertation in serum and brain samples have been reported. An age-related shift in the gut microbiota composition associated with its decreased diversity and stability observed in AD patients may significantly affect BA metabolism and signaling. Given recent evidence on BA neuroprotective and anti-inflammatory effects, new therapeutic targets have been explored including gut microbiota modulation by probiotics and dietary interventions, ursodeoxycholic acid supplementation, and use of BA receptor agonists.
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http://dx.doi.org/10.3233/JAD-210608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8673511PMC
January 2022

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis.

Neurogastroenterol Motil 2021 08;33(8):e14237

Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.

Background: Gastroparesis is a condition characterized by epigastric symptoms and delayed gastric emptying (GE) rate in the absence of any mechanical obstruction. The condition is challenging in clinical practice by the lack of guidance concerning diagnosis and management of gastroparesis.

Methods: A Delphi consensus was undertaken by 40 experts from 19 European countries who conducted a literature summary and voting process on 89 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation criteria. Consensus (defined as ≥80% agreement) was reached for 25 statements.

Results: The European consensus defined gastroparesis as the presence of symptoms associated with delayed GE in the absence of mechanical obstruction. Nausea and vomiting were identified as cardinal symptoms, with often coexisting postprandial distress syndrome symptoms of dyspepsia. The true epidemiology of gastroparesis is not known in detail, but diabetes, gastric surgery, certain neurological and connective tissue diseases, and the use of certain drugs recognized as risk factors. While the panel agreed that severely impaired gastric motor function is present in these patients, there was no consensus on underlying pathophysiology. The panel agreed that an upper endoscopy and a GE test are required for diagnosis. Only dietary therapy, dopamine-2 antagonists and 5-HT receptor agonists were considered appropriate therapies, in addition to nutritional support in case of severe weight loss. No consensus was reached on the use of proton pump inhibitors, other classes of antiemetics or prokinetics, neuromodulators, complimentary, psychological, or more invasive therapies. Finally, there was consensus that gastroparesis adversely impacts on quality of life and healthcare costs and that the long-term prognosis of gastroparesis depends on the cause.

Conclusions And Inferences: A multinational group of European experts summarized the current state of consensus on definition, symptom characteristics, pathophysiology, diagnosis, and management of gastroparesis.
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http://dx.doi.org/10.1111/nmo.14237DOI Listing
August 2021

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis.

United European Gastroenterol J 2021 04;9(3):287-306

Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.

Background: Gastroparesis is a condition characterized by epigastric symptoms and delayed gastric emptying (GE) rate in the absence of any mechanical obstruction. The condition is challenging in clinical practice by the lack of guidance concerning diagnosis and management of gastroparesis.

Methods: A Delphi consensus was undertaken by 40 experts from 19 European countries who conducted a literature summary and voting process on 89 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation criteria. Consensus (defined as ≥80% agreement) was reached for 25 statements.

Results: The European consensus defined gastroparesis as the presence of symptoms associated with delayed GE in the absence of mechanical obstruction. Nausea and vomiting were identified as cardinal symptoms, with often coexisting postprandial distress syndrome symptoms of dyspepsia. The true epidemiology of gastroparesis is not known in detail, but diabetes, gastric surgery, certain neurological and connective tissue diseases, and the use of certain drugs recognized as risk factors. While the panel agreed that severely impaired gastric motor function is present in these patients, there was no consensus on underlying pathophysiology. The panel agreed that an upper endoscopy and a GE test are required for diagnosis. Only dietary therapy, dopamine-2 antagonists and 5-HT receptor agonists were considered appropriate therapies, in addition to nutritional support in case of severe weight loss. No consensus was reached on the use of proton pump inhibitors, other classes of antiemetics or prokinetics, neuromodulators, complimentary, psychological, or more invasive therapies. Finally, there was consensus that gastroparesis adversely impacts on quality of life and healthcare costs and that the long-term prognosis of gastroparesis depends on the cause.

Conclusions And Inferences: A multinational group of European experts summarized the current state of consensus on definition, symptom characteristics, pathophysiology, diagnosis, and management of gastroparesis.
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http://dx.doi.org/10.1002/ueg2.12060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259275PMC
April 2021

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

United European Gastroenterol J 2021 04;9(3):307-331

Gastroenterology Unit, Departmento of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

Background: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis.

Methods: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements.

Results: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable.

Conclusions And Inferences: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
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http://dx.doi.org/10.1002/ueg2.12061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259261PMC
April 2021

The impact of probiotics on interactions within the microbiota-gut-lung triad in COVID-19.

Authors:
Agata Mulak

Int J Food Sci Nutr 2021 Jun 2;72(4):577-578. Epub 2021 Jan 2.

Department of Gastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland.

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http://dx.doi.org/10.1080/09637486.2020.1850651DOI Listing
June 2021

An Inverse Correlation of Serum Fibroblast Growth Factor 19 with Abdominal Pain and Inflammatory Markers in Patients with Ulcerative Colitis.

Gastroenterol Res Pract 2020 29;2020:2389312. Epub 2020 May 29.

Department of Gastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland.

Background And Aims: Bile acids (BA) play an important role in the modulation of numerous gut functions. Fibroblast growth factor 19 (FGF19) is the ileal hormone regulating BA homeostasis. The aim of the study was to evaluate serum FGF19 level and its correlation with clinical and endoscopic disease activity indices along with inflammatory biomarkers including serum CRP and fecal calprotectin levels in patients with ulcerative colitis (UC).

Methods: Fasting serum FGF19 level was measured using ELISA test in 16 patients with active UC (7 F, 9 M), 15 patients with nonactive UC (8 F, 7 M), and 19 healthy controls (11 F, 8 M). The disease activity was assessed based on the clinical and endoscopic evaluations as well as serum CRP and fecal calprotectin level measurement.

Results: The median serum FGF19 level was higher in patients with nonactive UC (175.3 pg/ml (108.7-342.3)) than in patients with active UC (114.3 pg/ml (68.9-155.3), = 0.093). The median FGF19 level in healthy controls amounted to 151.6 pg/ml (90.6-224.2), and there were no statistically significant differences between the patients with active and nonactive UC compared to the healthy controls. An inverse correlation was observed between FGF19 level and abdominal pain intensity ( = -0.48, = 0.007) as well as fecal calprotectin ( = -0.38, = 0.036) and CRP levels ( = -0.36, = 0.045). The serum FGF19 level was not correlated neither with clinical nor endoscopic disease activity indices.

Conclusions: The inverse correlations between FGF19 level and abdominal pain as well as inflammatory markers in UC may imply its potential analgesic and anti-inflammatory effects.
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http://dx.doi.org/10.1155/2020/2389312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275953PMC
May 2020

Recent Data on Irritable Bowel Syndrome from some Central and East European Countries.

J Gastrointestin Liver Dis 2020 06 3;29(2):247-250. Epub 2020 Jun 3.

Deptartment Gastroenterology, Grigore T Popa University of Medicine and Pharmacy Iasi, Romania.

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http://dx.doi.org/10.15403/jgld-2407DOI Listing
June 2020

Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study.

Gastroenterology 2021 01 12;160(1):99-114.e3. Epub 2020 Apr 12.

Dhaka Medical College & Hospital, Dhaka, Bangladesh.

Background & Aims: Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on health care systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents.

Methods: Data were collected via the Internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for Internet and household groups, so data analyses were conducted and reported separately.

Results: Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.3% persons who completed the Internet surveys (95% confidence interval [CI], 39.9-40.7) and 20.7% of persons who completed the household surveys (95% CI, 20.2-21.3). FGIDs were more prevalent among women than men, based on responses to the Internet survey (odds ratio, 1.7; 95% CI, 1.6-1.7) and household survey (odds ratio, 1.3; 95% CI, 1.3-1.4). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the Internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%).

Conclusions: In a large-scale multinational study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and health care use. Although the absolute prevalence was higher among Internet respondents, similar trends and relative distributions were found in people who completed Internet vs personal interviews.
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http://dx.doi.org/10.1053/j.gastro.2020.04.014DOI Listing
January 2021

An overview of the neuroendocrine system in Parkinson's disease: what is the impact on diagnosis and treatment?

Authors:
Agata Mulak

Expert Rev Neurother 2020 02 12;20(2):127-135. Epub 2019 Dec 12.

Department of Gastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland.

: A growing body of evidence indicates that neuroendocrine interactions may occur at all levels of the brain-gut-microbiota axis, which is directly involved in the pathogenesis of Parkinson's disease (PD).: The review presents some current and emerging concepts regarding the organization and functioning of the neuroendocrine system as well as the role of neuroendocrine disturbances in the pathophysiology and symptomatology of PD. The concept of the brain-gut-microbiota triad interactions in the neuroendocrine system and PD is proposed. In PD, dysregulation of the main neuroendocrine axes coordinated by the hypothalamus is accompanied by disruptions at the peripheral level, which involve enteroendocrine cells producing numerous neuropeptides. Moreover, the important role of the gut microbiota as a main coordinator of immune and neuroendocrine interactions is discussed. The potential diagnostic and therapeutic implications in the context of the recent developments in the fields of neuroendocrinology and neurodegeneration are also presented.: Unraveling complex neuroendocrine interactions in the course of PD may provide crucial diagnostic implications and novel therapeutic approaches including the application of gut neuropeptides and gut microbiota modification.
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http://dx.doi.org/10.1080/14737175.2020.1701437DOI Listing
February 2020

Fecal Calprotectin as a Marker of the Gut Immune System Activation Is Elevated in Parkinson's Disease.

Front Neurosci 2019 27;13:992. Epub 2019 Sep 27.

Department of Neurology, Wrocław Medical University, Wrocław, Poland.

Introduction: Alpha-synucleinopathy constituting a characteristic feature of Parkinson's disease (PD) occurs at all levels of the brain-gut axis including the enteric nervous system (ENS). Lesions in the ENS may be connected with gut inflammation, increased intestinal permeability and dysmotility contributing to the pathogenesis of PD and its gastrointestinal manifestations.

Aims: To evaluate fecal calprotectin and zonulin as biomarkers of gut inflammation and intestinal barrier dysfunction in PD patients.

Methods: Quantitative evaluation of fecal biomarkers was performed by ELISA tests in 35 PD patients and 20 healthy controls. Additionally, patients filled out a short questionnaire concerning gastrointestinal symptoms.

Results: Median fecal calprotectin level (μg/g) was significantly higher in PD patients compared to the controls: 54.5 (29.0-137.9) vs. 9.7 (5.2-23.3), < 0.0001. Applying age-related reference ranges, the increased fecal calprotectin level was found in 43% of PD patients and in none of the control subjects ( < 0.001). No correlation between fecal calprotectin level and PD duration was observed. No statistically significant difference between the groups regarding zonulin level was found. The most frequent bowel symptoms reported by PD patients included constipation (69% of subjects), feeling of incomplete evacuation (51%), bloating (51%), abdominal pain (20%), and alternating bowel movement pattern (17%).

Conclusion: The evaluation of fecal calprotectin level may be a useful tool to detect the signs of gut immune system activation present in a remarkable number of PD patients, also in the early stage of the disease. Calprotectin may constitute a critical link between amyloid formation and neuroinflammatory cascades serving as a prospective diagnostic and therapeutic target.
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http://dx.doi.org/10.3389/fnins.2019.00992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776883PMC
September 2019

Brain-Gut-Microbiota Axis in Alzheimer's Disease.

J Neurogastroenterol Motil 2019 Jan;25(1):48-60

Department of Gastroenterology and Hepatology, Wroclaw Medical University, Poland.

Disturbances along the brain-gut-microbiota axis may significantly contribute to the pathogenesis of neurodegenerative disorders. Alzheimer's disease (AD) is the most frequent cause of dementia characterized by a progressive decline in cognitive function associated with the formation of amyloid beta (Aβ) plaques and neurofibrillary tangles. Alterations in the gut microbiota composition induce increased permeability of the gut barrier and immune activation leading to systemic inflammation, which in turn may impair the blood-brain barrier and promote neuroinflammation, neural injury, and ultimately neurodegeneration. Recently, Aβ has also been recognized as an antimicrobial peptide participating in the innate immune response. However, in the dysregulated state, Aβ may reveal harmful properties. Importantly, bacterial amyloids through molecular mimicry may elicit cross-seeding of misfolding and induce microglial priming. The Aβ seeding and propagation may occur at different levels of the brain-gut-microbiota axis. The potential mechanisms of amyloid spreading include neuron-to-neuron or distal neuron spreading, direct blood-brain barrier crossing or via other cells as astrocytes, fibroblasts, microglia, and immune system cells. A growing body of experimental and clinical data confirms a key role of gut dysbiosis and gut microbiota-host interactions in neurodegeneration. The convergence of gut-derived inflammatory response together with aging and poor diet in the elderly contribute to the pathogenesis of AD. Modification of the gut microbiota composition by food-based therapy or by probiotic supplementation may create new preventive and therapeutic options in AD.
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http://dx.doi.org/10.5056/jnm18087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326209PMC
January 2019

Guidelines on the management of irritable bowel syndrome: In memory of Professor Witold Bartnik.

Prz Gastroenterol 2018 19;13(4):259-288. Epub 2018 Sep 19.

Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Subdivision, Central Clinical Hospital of the Ministry of the Interior, Warsaw, Poland.

These guidelines constitute an update of the previous "Recommendations on the management of irritable bowel syndrome" issued in 2008. They have been developed by a Task Force organized by the Governing Board of the Polish Society of Gastroenterology. They discuss, with particular emphasis on new scientific data covering papers published since 2008, the aetiology, epidemiology, clinical presentation, diagnostic principles and criteria for the diagnosis, and recommendations for the treatment of irritable bowel syndrome (IBS). The English-language acronym for the syndrome (IBS) has become popular in medical and popular scientific language. It is also widely recognized by patients who identify with this diagnosis. Therefore, in the discussed guidelines, this is what we will use.
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http://dx.doi.org/10.5114/pg.2018.78343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300851PMC
September 2018

A controversy on the role of short-chain fatty acids in the pathogenesis of Parkinson's disease.

Authors:
Agata Mulak

Mov Disord 2018 03 13;33(3):398-401. Epub 2018 Feb 13.

Department of Gastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland.

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http://dx.doi.org/10.1002/mds.27304DOI Listing
March 2018

Serotonin-Related Gene Variants in Patients with Irritable Bowel Syndrome and Depressive or Anxiety Disorders.

Gastroenterol Res Pract 2017 16;2017:4290430. Epub 2017 Aug 16.

Department of Gastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland.

Aim: To assess the association of six polymorphisms in serotonin-related genes with depressive or anxiety disorders in patients with irritable bowel syndrome (IBS).

Methods: The lifetime prevalence of depressive and anxiety disorders was assessed in 95 IBS patients (85% women) using the Munich version of the Composite International Diagnostic Interview (CIDI). IBS was diagnosed according to the Rome III criteria. HTTLPR polymorphism (rs4795541) was determined using PCR-based method. Single-nucleotide polymorphisms in (rs6295), (rs6313 and rs6311), (rs6318), and (rs1800532) were detected by minisequencing method.

Results: IBS patients with depressive disorders were characterized by higher frequency of 5-HTTLPR L allele in comparison to IBS patients with anxiety disorders. The lower frequency of 1438 A allele in was found in IBS patients with depressive disorders in comparison to IBS patients without mental disorders. The lower G allele frequency in rs6318 polymorphism among IBS patients with anxiety disorders was also observed.

Conclusions: Our results provide further evidence for the involvement of rs4795541 and rs6311 polymorphisms in the pathophysiology of depressive disorders in IBS patients. The new findings indicate that rs6318 polymorphism may be associated with the susceptibility to anxiety disorders in IBS patients.
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http://dx.doi.org/10.1155/2017/4290430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603736PMC
August 2017

The role of bile acids in the pathogenesis of bowel diseases.

Postepy Hig Med Dosw (Online) 2017 Aug;71(1):737-746

Katedra i Klinika Gastroenterologii i Hepatologii, Uniwersytet Medyczny we Wrocławiu.

Bile acids not only play a cardinal role in the digestion and absorption of fat and fat-soluble vitamins, but also significantly affect gastrointestinal motor, sensory and secretory functions, intestinal barrier permeability and the regulation of the inflammatory response. The results of recent studies have revealed complex interactions between bile acids and the gut microbiota. In addition, bile acids also play a role of signaling molecules regulating the activity of lipid and glucose metabolic pathways, as well as a role of ligands for transcription factors. Genetic factors associated with the regulation of bile acid synthesis, transport and action may significantly influence gastrointestinal function and predispose to diarrhea resulting from bile acid malabsorption. Methods used in the diagnosis of bile acid malabsorption include 75selenium-homotaurocholic acid test, serum C4 and fibroblast growth factor 19 (FGF19), as well as fecal bile acid levels. The paper presents the latest data on the role of bile acid in the pathogenesis of irritable bowel syndrome, inflammatory bowel diseases and colorectal cancer. Advances in the treatment of disturbances in bile acids absorption and synthesis are also presented. A better understanding of molecular mechanisms regulating bile acid action may have implication for colorectal cancer prevention.
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http://dx.doi.org/10.5604/01.3001.0010.3852DOI Listing
August 2017

Pancreatic duct stones: A report on 16 cases.

Adv Clin Exp Med 2017 Jul;26(4):609-613

Department of Gastroenterology and Hepatology, Wroclaw Medical University, Poland.

Background: Pancreatolithiasis occurs in less than 1% of the general population and is mainly recognized in patients with chronic pancreatitis. Selection of the appropriate treatment method depends on the location, size and number of stones.

Objectives: The aim of the study was to analyze data concerning patients with pancreatic duct stones who were hospitalized at Wroclaw Medical University's Department of Gastroenterology and Hepatology from 2010 to 2014.

Material And Methods: The study presents data on 16 patients with pancreatic duct stones, who constituted 7% of all 228 patients with chronic pancreatitis hospitalized at the Department in the study period. The clinical data were compared with findings reported in the literature.

Results: Epigastric pain was the most common symptom reported by patients with pancreatolithiasis. The sensitivity of imaging tests in the diagnosis of pancreatic duct stones was as follows: abdominal ultrasonography - 31%, endoscopic retrograde cholangiopancreatography (ERCP) - 67%, computed tomography - 71%, endoscopic ultrasonography - 73%. In 6 patients ERCP and sphincterotomy were performed along with stenting of the main pancreatic duct. Three other subjects were qualified for surgical treatment. In 7 selected patients conservative treatment and further observation were applied.

Conclusions: Endoscopic ultrasonography is characterized by high sensitivity in the diagnosis of pancreatic duct stones. ERCP is the first-line treatment in the case of a small number of stones with sizes below 5 mm located in the head or body of the pancreas. In the case of stones with sizes ≥ 5 mm, extracorporeal shock wave lithotripsy should be performed before endoscopic drainage during ERCP. Stenosis of the main pancreatic duct is the key risk factor for the recurrence of pancreatolithiasis.
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http://dx.doi.org/10.17219/acem/62687DOI Listing
July 2017

Diagnostic challenges in celiac disease.

Adv Clin Exp Med 2017 Jul;26(4):729-737

Department of Gastroenterology and Hepatology, Wroclaw Medical University, Poland.

Diagnosis of celiac disease in adults is currently based on serologic tests in combination with histopathological assessment of small intestinal biopsy specimens. High titers of celiac-specific antibodies in immunocompetent patients with villous atrophy in a good quality biopsy sample allow us to state a confident diagnosis. The relief of symptoms and histological improvement after embarking on a gluten free diet further support the initial diagnosis. However, in some cases, these conditions are not fulfilled, which requires a critical evaluation of laboratory and histopathology results and a consideration of other potential causes for the observed pathologies. To avoid diagnostic uncertainty, both biopsy and laboratory testing should be performed on a diet containing gluten. Immune deficiency, cross reaction of antibodies and possibilities of seronegative or latent celiac disease should be considered while evaluating serology results. Uneven distribution and variable intensity of histopathological changes in the small intestine along with multiple disorders presenting a similar specimen image may lead to invalid biopsy results. Additional laboratory testing and careful examination of a patient's history may deliver important data for a differential diagnosis and a more specific biopsy evaluation. Persistence or recurrence of symptoms, despite the ongoing treatment, requires a revision of the initial diagnosis, an evaluation of the gluten free diet and a search for concurrent disorders or complications.
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http://dx.doi.org/10.17219/acem/62452DOI Listing
July 2017

Inadequate seroprotection against hepatitis B virus and one detected case of hepatitis C virus infection among patients with inflammatory bowel disease.

Eur J Gastroenterol Hepatol 2016 Jun;28(6):628-32

Departments of aGastroenterology and Hepatology bPaediatrics and Infectious Diseases, Wroclaw Medical University, Wroclaw, Poland.

Objectives: The prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among patients with inflammatory bowel disease (IBD) from central and eastern European countries is unknown. Postvaccination HBV immunity in an immunocompromised host may wane. The aims of the study were as follows: to assess the immune status for HBV and HCV among IBD patients, the level of HBV seroprotection, and to compare the immune status of patients who received mandatory versus recommended HBV vaccination.

Materials And Methods: Serological markers of HBV and HCV (anti-HBs, anti-HBc, HBsAg, and anti-HCV) were determined in 147 consecutive IBD patients. An anti-HBs of 10 IU/l or more was considered as immunity to HBV infection.

Results: HBV infection was detected in 21 patients, whereas 11 of them recalled previous HBV vaccination. Sixty-eight noninfected patients had a level of anti-HBs 10 IU/l or more and only 29% reached the cut-off level of 100 IU/l. Among patients vaccinated obligatorily, two patients had previous HBV infection and 15% did not have an adequate seroprotection against HBV. Patients who received a mandatory HBV vaccine more frequently had a protective anti-HBs level than those vaccinated voluntarily (P<0.001). One positive anti-HCV result was found.

Conclusion: A mandatory HBV vaccination significantly increased the number of patients effectively protected against HBV; however, a remarkable number of vaccinated IBD patients had inadequate HBV seroprotection. All IBD patients should be screened for HBV and HCV infections and monitored for anti-HBs titers.
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http://dx.doi.org/10.1097/MEG.0000000000000613DOI Listing
June 2016

The HLA-DQβ1 insertion is a strong achalasia risk factor and displays a geospatial north-south gradient among Europeans.

Eur J Hum Genet 2016 08 6;24(8):1228-31. Epub 2016 Jan 6.

Department of Gastroenterology, DKD Helios Clinic Wiesbaden, Wiesbaden, Germany.

Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQβ1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQβ1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10(-04), Sweden P=7.44 × 10(-05)). Combining all five European data sets - Central Europe, Italy, Spain, Poland and Sweden - the insertion is achalasia associated with Pcombined=1.67 × 10(-35). In addition, we observe that the frequency of the insertion shows a geospatial north-south gradient. The insertion is less common in northern (around 6-7% in patients and 2% in controls from Sweden and Poland) compared with southern Europeans (~16% in patients and 8% in controls from Italy) and shows a stronger attributable risk in the southern European population. Our study provides evidence that the prevalence of achalasia may differ between populations.
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http://dx.doi.org/10.1038/ejhg.2015.262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970678PMC
August 2016

Lessons learned--resolving the enigma of genetic factors in IBS.

Nat Rev Gastroenterol Hepatol 2016 Feb 4;13(2):77-87. Epub 2016 Jan 4.

Institute of Human Genetics, Department of Human Molecular Genetics, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.

IBS is the most prevalent functional gastrointestinal disorder and phenotypically characterized by chronic abdominal discomfort, pain and altered defecation patterns. The pathophysiology of IBS is multifactorial, albeit with a substantial genetic component. To date, studies using various methodologies, ranging from family and twin studies to candidate gene approaches and genome-wide association studies, have identified several genetic variants in the context of IBS. Yet, despite enlarged sample sizes, increased statistical power and meta-analyses in the past 7 years, positive associations are still scarce and/or have not been reproduced. In addition, epigenetic and pharmacogenetic approaches remain in their infancy. A major hurdle is the lack of large homogenized case-control cohorts recruited according to standardized and harmonized criteria. The COST Action BM1106 GENIEUR (GENes in Irritable Bowel Syndrome Research Network EURope) has been established to address these obstacles. In this Review, the (epi)genetic working group of GENIEUR reports on the current state-of-the-art in the field, highlights fundamental flaws and pitfalls in current IBS (epi)genetic research and provides a vision on how to address and improve (epi)genetic approaches in this complex disorder in the future.
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http://dx.doi.org/10.1038/nrgastro.2015.206DOI Listing
February 2016

Brain-gut-microbiota axis in Parkinson's disease.

World J Gastroenterol 2015 Oct;21(37):10609-20

Agata Mulak, Department of Gastroenterology and Hepatology, Wroclaw Medical University, 50-556 Wroclaw, Poland.

Parkinson's disease (PD) is characterized by alpha-synucleinopathy that affects all levels of the brain-gut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological, neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding. Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gut-microbiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.
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http://dx.doi.org/10.3748/wjg.v21.i37.10609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588083PMC
October 2015

Genetic polymorphism of ABCB1 gene (C3435T) in patients with inflammatory bowel diseases. Is there any gender dependency?

Pharmacol Rep 2015 Apr 18;67(2):294-8. Epub 2014 Oct 18.

Department of Clinical Pharmacology Wroclaw Medical University, Wrocław, Poland. Electronic address:

Background: In recent years, an increasing incidence of inflammatory bowel disease (IBD) has been reported, mainly as Crohn's disease (CD) and ulcerative colitis (UC). The individual susceptibility, the disease's course and response to the applied therapy is likely due to genetic factors such as ABCB1 gene mutations, exemplified by C3435T polymorphism. The aim of the study was to evaluate the distribution of C3435T polymorphism regarding the gender in IBD patients and control subjects from Lower Silesia region and its possible association with IBD susceptibility.

Methods: The research was conducted in groups of 61 IBD patients and 101 healthy subjects from the Lower Silesia region. Polymorphism of C3435T was determined using PCR-RFLP method.

Results: Frequency distributions of C3435T genotype and of 3435T or 3435C gene alleles of IBD, CD or UC patients were compared to control group; each treated as a whole or split further by gender. The statistically significant correlation was discovered between gender and C3435T genotype both for IBD and CD patients, with 3435CT heterozygote prevailing in IBD and CD males. Odds ratio calculations revealed statistically significant difference for the 3435CT genotype between control and: IBD group considered as a whole; IBD males; CD males; and for 3435TT variant between control and IBD males. Conclusions. The 3435CT genotype could be a risk factor for IBD and CD in men. The 3435TT genotype in males seems to be associated with the lower chance of IBD presence.
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http://dx.doi.org/10.1016/j.pharep.2014.09.014DOI Listing
April 2015

The lifetime prevalence of anxiety disorders among patients with irritable bowel syndrome.

Adv Clin Exp Med 2014 Nov-Dec;23(6):987-92

Department of Psychiatry, Wroclaw Medical University, Poland.

Background: The prevalence of irritable bowel syndrome (IBS), the most common functional gastrointestinal disorder, ranges from 10% to 20% in the general population. It is estimated that from 40% to 90% of persons with a diagnosis of IBS suffer from mental disorders, mainly anxiety and depressive disorders.

Objectives: The aim of the study was to assess the lifetime prevalence of anxiety disorders in IBS patients and to compare it with the prevalence of these disorders in a control group of patients with gastroesophageal reflux disease (GERD).

Material And Methods: The study included 106 patients with IBS and 53 patients with GERD. IBS was diagnosed according to the Rome II criteria after a basic evaluation to exclude an organic disease. Anxiety disorders were diagnosed using the Composite International Diagnostic Interview (CIDI) in accordance with ICD-10 diagnostic criteria.

Results: Anxiety disorders during the patient's lifetime were diagnosed in 50 IBS patients (47%). Specific phobias occurred in 23.5% of them, social phobias in 10.4%, generalized anxiety disorder in 10.4%, panic disorder in 3.8% and agoraphobia in 8.5%. In the control group with GERD, anxiety disorders during the subject's lifetime were diagnosed in 30% of the group. The difference in the prevalence of anxiety disorders between patients with IBS and GERD was statistically significant (p<0.05).

Conclusions: The lifetime prevalence of anxiety disorders in IBS patients was higher than in the control group with GERD (47% vs. 30%). The prevalence rate of anxiety disorders in the control group with GERD was similar to the prevalence rate in the general population.
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http://dx.doi.org/10.17219/acem/37356DOI Listing
April 2015

A 'cocoon immunization strategy' among patients with inflammatory bowel disease.

Eur J Gastroenterol Hepatol 2015 Mar;27(3):249-53

Departments of aPediatrics and Infectious Diseases bGastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland.

Background And Aims: A 'cocoon strategy' is defined as the strategy of protecting vulnerable patients from infectious diseases by vaccinating those in close contact with them. In our study, we evaluate the vaccination status among children living with patients with inflammatory bowel disease (IBD) to determine the realization of the cocoon strategy and to identify characteristics associated with pediatric vaccine refusal.

Patients And Methods: A self-completed survey was conducted on 136 hospitalized patients with IBD. The survey comprised questions about household child vaccination coverage, the reasons for vaccine refusal, and the history of infectious diseases among the patients.

Results: Fifty-six patients reported living with children. Forty percent of children were vaccinated with at least one of the recommended vaccines. Most frequently, children received pneumococcal (26%) and rotaviruses (22%) vaccines. The most common reason for nonimmunization was patients' opinion that immunizations are not necessary for them (52%). There was a statistically significant association between the nonreimbursed vaccines coverage and the educational level of the patients (P<0.0001). Despite the fact that 28% of the patients could not definitively recall varicella infection, none of them and none of the children in their household had been vaccinated against chickenpox.

Conclusion: The use of nonmandatory vaccines recommended in family members of patients with IBD is insufficient. Further vaccine promotion and education of patients as well as their healthcare providers is required. A particular concern is associated with the pneumococcal, influenza, rotaviruses, and varicella infections. Nonimmunized and varicella-zoster virus-seronegative patients should be vaccinated, and in case of immunosuppression, vaccination of children in the household is required.
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http://dx.doi.org/10.1097/MEG.0000000000000280DOI Listing
March 2015

Selective agonists of somatostatin receptor subtype 1 or 2 injected peripherally induce antihyperalgesic effect in two models of visceral hypersensitivity in mice.

Peptides 2015 Jan 5;63:71-80. Epub 2014 Nov 5.

Department of Medicine, CURE: Digestive Diseases Research Center and Oppenheimer Family Center for Neurobiology of Stress, Digestive Diseases Division at the University of California Los Angeles and VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA. Electronic address:

Somatostatin interacts with five G-protein-coupled receptor (sst1-5). Octreotide, a stable sst2≫3≥5 agonist, exerts a visceral anti-hyperalgesic effect in experimental and clinical studies. Little is known on the receptor subtypes involved. We investigated the influence of the stable sst1-5 agonist, ODT8-SST and selective receptor subtype peptide agonists (3 or 10μg/mouse) injected intraperitoneally (ip) on visceral hypersensitivity in mice induced by repeated noxious colorectal distensions (four sets of three CRD, each at 55mmHg) or corticotropin-releasing factor receptor 1 agonist, cortagine given between two sets of graded CRD (15, 30, 45, and 60mmHg, three times each pressure). The mean visceromotor response (VMR) was assessed using a non-invasive manometry method and values were expressed as percentage of the VMR to the 1st set of CRD baseline or to the 60mmHg CRD, respectively. ODT8-SST (10μg) and the sst2 agonist, S-346-011 (3 and 10μg) prevented mechanically induced visceral hypersensitivity in the three sets of CRD, the sst1 agonist (10μg) blocked only the 2nd set and showed a trend at 3μg while the sst4 agonist had no effect. The selective sst2 antagonist, S-406-028 blocked the sst2 agonist but not the sst1 agonist effect. The sst1 agonist (3 and 10μg) prevented cortagine-induced hypersensitivity to CRD at each pressure while the sst2 agonist at 10μg reduced it. These data indicate that in addition to sst2, the sst1 agonist may provide a novel promising target to alleviate visceral hypersensitivity induced by mechanoreceptor sensitization and more prominently, stress-related visceral nociceptive sensitization.
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http://dx.doi.org/10.1016/j.peptides.2014.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385413PMC
January 2015

Sex hormones in the modulation of irritable bowel syndrome.

World J Gastroenterol 2014 Mar;20(10):2433-48

Agata Mulak, Department of Gastroenterology and Hepatology, Wroclaw Medical University, 50-556 Wroclaw, Poland.

Compelling evidence indicates sex and gender differences in epidemiology, symptomatology, pathophysiology, and treatment outcome in irritable bowel syndrome (IBS). Based on the female predominance as well as the correlation between IBS symptoms and hormonal status, several models have been proposed to examine the role of sex hormones in gastrointestinal (GI) function including differences in GI symptoms expression in distinct phases of the menstrual cycle, in pre- and post-menopausal women, during pregnancy, hormonal treatment or after oophorectomy. Sex hormones may influence peripheral and central regulatory mechanisms of the brain-gut axis involved in the pathophysiology of IBS contributing to the alterations in visceral sensitivity, motility, intestinal barrier function, and immune activation of intestinal mucosa. Sex differences in stress response of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, neuroimmune interactions triggered by stress, as well as estrogen interactions with serotonin and corticotropin-releasing factor signaling systems are being increasingly recognized. A concept of "microgenderome" related to the potential role of sex hormone modulation of the gut microbiota is also emerging. Significant differences between IBS female and male patients regarding symptomatology and comorbidity with other chronic pain syndromes and psychiatric disorders, together with differences in efficacy of serotonergic medications in IBS patients confirm the necessity for more sex-tailored therapeutic approach in this disorder.
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http://dx.doi.org/10.3748/wjg.v20.i10.2433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3949254PMC
March 2014

Serum and urine metabolomic fingerprinting in diagnostics of inflammatory bowel diseases.

World J Gastroenterol 2014 Jan;20(1):163-74

Tomasz Dawiskiba, Jan Skóra, Piotr Barć, Krzysztof Korta, Kornel Pormańczuk, Przemyslaw Szyber, Department of Vascular, General and Transplantation Surgery, Wroclaw Medical University, 50-556 Wroclaw, Poland.

Aim: To evaluate the utility of serum and urine metabolomic analysis in diagnosing and monitoring of inflammatory bowel diseases (IBD).

Methods: Serum and urine samples were collected from 24 patients with ulcerative colitis (UC), 19 patients with the Crohn's disease (CD) and 17 healthy controls. The activity of UC was assessed with the Simple Clinical Colitis Activity Index, while the activity of CD was determined using the Harvey-Bradshaw Index. The analysis of serum and urine samples was performed using proton nuclear magnetic resonance (NMR) spectroscopy. All spectra were exported to Matlab for preprocessing which resulted in two data matrixes for serum and urine. Prior to the chemometric analysis, both data sets were unit variance scaled. The differences in metabolite fingerprints were assessed using partial least-squares-discriminant analysis (PLS-DA). Receiver operating characteristic curves and area under curves were used to evaluate the quality and prediction performance of the obtained PLS-DA models. Metabolites responsible for separation in models were tested using STATISTICA 10 with the Mann-Whitney-Wilcoxon test and the Student's t test (α = 0.05).

Results: The comparison between the group of patients with active IBD and the group with IBD in remission provided good PLS-DA models (P value 0.002 for serum and 0.003 for urine). The metabolites that allowed to distinguish these groups were: N-acetylated compounds and phenylalanine (up-regulated in serum), low-density lipoproteins and very low-density lipoproteins (decreased in serum) as well as glycine (increased in urine) and acetoacetate (decreased in urine). The significant differences in metabolomic profiles were also found between the group of patients with active IBD and healthy control subjects providing the PLS-DA models with a very good separation (P value < 0.001 for serum and 0.003 for urine). The metabolites that were found to be the strongest biomarkers included in this case: leucine, isoleucine, 3-hydroxybutyric acid, N-acetylated compounds, acetoacetate, glycine, phenylalanine and lactate (increased in serum), creatine, dimethyl sulfone, histidine, choline and its derivatives (decreased in serum), as well as citrate, hippurate, trigonelline, taurine, succinate and 2-hydroxyisobutyrate (decreased in urine). No clear separation in PLS-DA models was found between CD and UC patients based on the analysis of serum and urine samples, although one metabolite (formate) in univariate statistical analysis was significantly lower in serum of patients with active CD, and two metabolites (alanine and N-acetylated compounds) were significantly higher in serum of patients with CD when comparing jointly patients in the remission and active phase of the diseases. Contrary to the results obtained from the serum samples, the analysis of urine samples allowed to distinguish patients with IBD in remission from healthy control subjects. The metabolites of importance included in this case up-regulated acetoacetate and down-regulated citrate, hippurate, taurine, succinate, glycine, alanine and formate.

Conclusion: NMR-based metabolomic fingerprinting of serum and urine has the potential to be a useful tool in distinguishing patients with active IBD from those in remission.
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http://dx.doi.org/10.3748/wjg.v20.i1.163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886005PMC
January 2014
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