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There is a huge need to search for new treatment options and potential biomarkers of therapeutic response to antidepressant treatment. Depression and metabolic syndrome often coexist, while a pathophysiological overlap, including microbiota changes, may play a role. The paper presents a study protocol that aims to assess the effect of probiotic supplementation on symptoms of depression, anxiety and stress, metabolic parameters, inflammatory and oxidative stress markers, as well as fecal microbiota in adult patients with depressive disorders depending on the co-occurrence of metabolic syndrome. The trial will be a four-arm, parallel-group, prospective, randomized, double-blind, controlled design that will include 200 participants and will last 20 weeks (ClinicalTrials.gov identifier: NCT04756544). The probiotic preparation will contain Lactobacillus helveticus Rosell®-52, Bifidobacterium longum Rosell®-175. We will assess the level of depression, anxiety and stress, quality of life, blood pressure, body mass index and waist circumference, white blood cells count, serum levels of C-reactive protein, high-density lipoprotein (HDL) cholesterol, triglycerides, fasting glucose, fecal microbiota composition and the level of some fecal microbiota metabolites, as well as serum inflammatory markers and oxidative stress parameters. The proposed trial may establish a safe and easy-to-use adjunctive treatment option in a subpopulation of depressive patients only partially responsive to pharmacologic therapy.

There is a huge need to search for new treatment options and potential biomarkers of therapeutic response to antidepressant treatment. Depression and metabolic syndrome often coexist while pathophysiological overlap, including microbiota changes, may play a role. The aim of the study is to assess the effect of probiotic supplementation on symptoms of depression, anxiety and stress, metabolic parameters, inflammation and oxidative stress markers, and faecal microbiota in adult patients with depressive disorders depending on the co-occurance of MetS. The trial will be a four-arm, parallel group, prospective, randomized, double-blind, controlled design that will include 200 participants and will last 20 weeks. The probiotic preparation will contain Lactobacillus helveticus Rosell®-52, Bifidobacterium longum Rosell®-175. We will assess the level of depression, anxiety and stress, quality of life, blood pressure, body mass index and waist circumference, white blood cells count, serum levels of C-reactive protein, HDL cholesterol, triglicerides, fasting glucose, faecal microbiota composition and the level of some faecal microbiota metabolites, as well as inflammation markers and oxidative stress parameters in serum. The trial may establish a safe and easy-to-use treatment option as an adjunct in a subpopulation of depressive patients only partially responsive to pharmacologic treatment. (ClinicalTrials.gov identifier: ).

Background The intestinal barrier plays an important role in the defense against infections, and nutritional, endocrine, and immune functions. The gut microbiota playing an important role in development of the gastrointestinal tract can impact intestinal permeability and immunity during early life, but data concerning this problem are scarce. Methods We analyzed the microbiota in fecal samples (101 samples in total) collected longitudinally over 24 months from 21 newborns to investigate whether the markers of small intestinal paracellular permeability (zonulin) and immune system development (calprotectin) are linked to the gut microbiota. The results were validated using data from an independent cohort that included the calprotectin and gut microbiota in children during the first year of life. Results Zonulin levels tended to increase for up to 6 months after childbirth and stabilize thereafter remaining at a high level while calprotectin concentration was high after childbirth and began to decline from 6 months of life. The gut microbiota composition and the related metabolic potentials changed during the first 2 years of life and were correlated with zonulin and calprotectin levels. Faecal calprotectin correlated inversely with alpha diversity (Shannon index, r = − 0.30, FDR P (Q) = 0.039). It also correlated with seven taxa; i.a. negatively with Ruminococcaceae (r = − 0.34, Q = 0.046), and Clostridiales (r = − 0.34, Q = 0.048) and positively with Staphylococcus (r = 0.38, Q = 0.023) and Staphylococcaceae (r = 0.35, Q = 0.04), whereas zonulin correlated with 19 taxa; i.a. with Bacillales (r = − 0.52, Q = 0.0004), Clostridiales (r = 0.48, Q = 0.001) and the Ruminococcus (torques group) (r = 0.40, Q = 0.026). When time intervals were considered only changes in abundance of the Ruminococcus (torques group) were associated with changes in calprotectin (β = 2.94, SE = 0.8, Q = 0.015). The dynamics of stool calprotectin was negatively associated with changes in two MetaCyc pathways: pyruvate fermentation to butanoate (β = − 4.54, SE = 1.08, Q = 0.028) and Clostridium acetobutylicum fermentation (β = − 4.48, SE = 1.16, Q = 0.026). Conclusions The small intestinal paracellular permeability, immune system-related markers and gut microbiota change dynamically during the first 2 years of life. The Ruminococcus (torques group) seems to be especially involved in controlling paracellular permeability. Staphylococcus, Staphylococcaceae, Ruminococcaceae, and Clostridiales, may be potential biomarkers of the immune system. Despite observed correlations their clear causation and health consequences were not proven. Mechanistic studies are required. Graphic abstract

Previous studies have reported on the relationship between gut microbiota and major depressive disorder (MDD). However, there remain gaps in literature concerning the role of the intestinal barrier and microflora in the pathogenesis of depression. This study analyzes the potential causative relationship between gut microbiota and inflammatory and gut integrity markers and clinical symptoms in inpatients with depressive episodes. Sixteen inpatients (50% females) being treated with escitalopram (5–20 mg daily) in standardized conditions were included in the study. The composition of fecal microbiota was evaluated at baseline and endpoint using 16S rRNA sequencing. A significant correlation between depression severity was found, as measured with HDRS24 (Hamilton Depression Rating Scale-24 item), and the following abundance in bacteria: positive correlation with Paraprevotella (r = 0.80, q = 0.012), strong, negative correlations with Clostridiales (r = −0.70, q = 0.016), Clostridia (r = −0.71, q = 0.026), Firmicutes (r = −0.67. q = 0.032), and the RF32 order (r = −0.70, p = 0.016) in the Alphaproteobacteria (r = −0.66, q = 0.031). After six weeks of treatment, clinical outcomes were found to have a negative correlation with levels of plasma intestinal fatty acid-binding protein (IFABP) at the beginning of the study. Still they had a positive correlation with changes in fecal calprotectin during hospitalization. In conclusion, gut microbiota was associated with the severity of depressive symptoms. However, these findings do not serve as predictors of symptomatic improvement during antidepressant treatment in inpatient treatment for MDD. In turn, intestinal integrity and inflammation markers were associated with the response to treatment of patients with MDD and symptom severity. Additional studies are needed to confirm and extend these findings.

Immaturity in digestive-tract motor function and altered intestinal microbiome may play roles in pathogenesis of infantile colic. We assessed the impact of probiotic therapy on crying duration day, in newborns experiencing colic attacks. The PubMed, Embase, Cinnahl, Web of Science databases, and a clinical trials registry (ClinicalTrials.gov) were searched from inception until 12/02/2020. Random-effects meta-analyses were used to derive standardized mean differences/differences in means and risk ratios. We included 16 studies, which involved 1319 newborns aged up to 6 months. Lactobacillus reuteri strain DSM17938 was administered predominantly (n = 10). Probiotic intervention reduced the duration of crying (standardized mean difference = −2.012, 95% confidence interval: −2.763 to −1.261, z = −5.25, p < 0.0001). The probability of at least a 50% reduction in crying duration was at least 1.98 times higher in the intervention group than in controls (Z = 4.80, p < 0.0001). The effects of the intervention were not significantly affected by the risk of bias assessment, percentage of breastfed infants, and duration of the study. In 11 studies, data concerning gut microbiota composition and function and/or immunological markers were given. Probiotics significantly shortened the crying duration, but a causal relationship between the modulatory effect of probiotics on microbiota and the immune system has not been confirmed.

Factors affecting the intestinal-barrier permeability of newborns, such as body mass index (BMI), nutrition and antibiotics, are assumed to affect intestinal-barrier permeability in the first two years of life. This study assessed 100 healthy, full-term newborns to 24 months old. Faecal zonulin/calprotectin concentrations were measured at 1, 6, 12, 24 months as gut-permeability markers. Zonulin concentrations increased between 1 and 12 months (medians: 114.41, 223.7 ng/mL, respectively), whereas calprotectin concentrations decreased between one and six months (medians: 149. 29, 109.28 &micro, g/mL), both then stabilized (24 months: 256.9 ng/mL zonulin, 59.5 &micro, g/mL calprotectin). In individual children, high levels at one month gave high levels at older ages (correlations: calprotectin: between 1 and 6 or 12 months: correlation coefficient (R) = 0.33, statistical significance (p) = 0.0095, R = 0.28, p = 0.032, zonulin: between 1 and 24 months: R = 0.32, p = 0.022, respectively). Parameters which gave marker increases: antibiotics during pregnancy (calprotectin, six months: by 80%, p = 0.038, 12 months: by 48%, p = 0.028), vaginal birth (calprotectin: 6 months: by 140%, p = 0.005), and &gt, 5.7 pregnancy-BMI increase (zonulin: 12 months: by 74%, p = 0.049). Conclusions: &ldquo, Closure of the intestines&rdquo, is spread over time and begins between the sixth and twelfth month of life. Antibiotic therapy, BMI increase &gt, 5.7 during pregnancy and vaginal birth are associated with increased intestinal permeability during the first two years of life. Stool zonulin and calprotectin concentrations were much higher compared with previous measurements at older ages, clinical interpretation and validation are needed (no health associations found).

The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has been predominantly linked to respiratory distress syndrome, but gastrointestinal symptoms and hepatic injury have also been reported. The mechanism of liver injury is poorly understood and may result as a consequence of viral hepatitis, systemic inflammatory response, gut barrier and microbiome alterations, intensive care treatment or drug toxicity. The incidence of hepatopathy among patients with coronavirus disease 2019 (COVID-19) is unclear, but studies have reported liver injury in patients with SARS and Middle East respiratory syndrome (MERS). We aimed to systematically review data on the prevalence of hepatic impairments and their clinical course in SARS and MERS Coronaviridae infections. A systematic literature search (PubMed/Embase/Cinahl/Web of Science) according to preferred reporting items for systematic review and meta-analysis protocols (PRISMA) was conducted from database inception until 17/03/2020 for studies that evaluated the incidence of hepatic abnormalities in SARS CoV-1, SARS CoV-2 and MERS infected patients with reported liver-related parameters. A total of forty-three studies were included. Liver anomalies were predominantly mild to moderately elevated transaminases, hypoalbuminemia and prolongation of prothrombin time. Histopathology varied between non-specific inflammation, mild steatosis, congestion and massive necrosis. More studies to elucidate the mechanism and importance of liver injury on the clinical course and prognosis in patients with novel SARS-CoV-2 infection are warranted.

Current treatment of major depressive disorder (MDD) often does not achieve full remission of symptoms. Therefore, new forms of treatment and/or adjunct therapy are needed. Evidence has confirmed the modulation of the gut–brain–microbiota axis as a promising approach in MDD patients. The overall purpose of the SANGUT study—a 12-week, randomized, double-blind, and placebo-controlled Study Evaluating the Effect of Probiotic Supplementation on the Mental Status, Inflammation, and Intestinal Barrier in Major Depressive Disorder Patients Using Gluten-free or Gluten-containing Diet — is to determine the effect of interventions focused on the gut-brain-microbiota axis in a group of MDD patients. A total of 120 outpatients will be equally allocated into one of four groups: (1) probiotic supplementation+gluten-free diet group (PRO-GFD), (2) placebo supplementation+ gluten-free diet group (PLA-GFD), (3) probiotic supplementation+ gluten containing diet group (PRO-GD), and (4) placebo supplementation+gluten containing diet group (PLA-GD). PRO groups will receive a mixture of psychobiotics (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175), and GFD groups will follow a gluten-free diet. The intervention will last 12 weeks. The primary outcome measure is change in wellbeing, whereas the secondary outcome measures include physiological parameters. Microbiota and its metabolites have the potential to influence CNS function. Probiotics may restore the eubiosis within the gut while a gluten-free diet, via changes in the microbiota profile and modulation of intestinal permeability, may alter the activity of microbiota-gut-brain axis previously found to be associated with the pathophysiology of depression. It is also noteworthy that microbiota being able to digest gluten may play a role in formation of peptides with different immunogenic capacities. Thus, the combination of a gluten-free diet and probiotic supplementation may inhibit the immune-inflammatory cascade in MDD course and improve both psychiatric and gut barrier-associated traits. NCT03877393 .

One very promising hypothesis of Major Depressive Disorder (MDD) pathogenesis is the gut-brain axis (GBA) dysfunction, which can lead to subclinical inflammation, hypothalamic–pituitary (HPA) axis dysregulation, and altered neural, metabolic and endocrine pathways. One of the most important parts of GBA is gut microbiota, which was shown to regulate different functions in the central nervous system (CNS). The purpose of this scoping review was to present the current state of research on the relationship between MDD and gut microbiota and extract causal relationships. Further, we presented the relationship between the use of probiotics and antidepressants, and the microbiota changes. We evaluated the data from 27 studies aimed to investigate microbial fingerprints associated with depression phenotype. We abstracted data from 16 and 11 observational and clinical studies, respectively; the latter was divided into trials evaluating the effects of psychiatric treatment (n = 3) and probiotic intervention (n = 9) on the microbiome composition and function. In total, the data of 1187 individuals from observational studies were assessed. In clinical studies, there were 490 individuals analysed. In probiotic studies, 220 and 218 patients with MDD received the intervention and non-active study comparator, respectively. It was concluded that in MDD, the microbiota is altered. Although the mechanism of this relationship is unknown, we hypothesise that the taxonomic changes observed in patients with MDD are associated with bacterial proinflammatory activity, reduced Schort Chain Fatty Acids (SCFAs) production, impaired intestinal barrier integrity and neurotransmitter production, impaired carbohydrates, tryptophane and glutamate metabolic pathways. However, only in few publications this effect was confirmed by metagenomic, metabolomic analysis, or by assessment of immunological parameters or intestinal permeability markers. Future research requires standardisation process starting from patient selection, material collection, DNA sequencing, and bioinformatic analysis. We did not observe whether antidepressive medications influence on gut microbiota, but the use of psychobiotics in patients with MDD has great prospects; however, this procedure requires also standardisation and thorough mechanistic research. The microbiota should be treated as an environmental element, which considers the aetiopathogenesis of the disease and provides new possibilities for monitoring and treating patients with MDD.

Accumulating evidence indicates that patients with severe mental disorders, including major depression, bipolar disorder and schizophrenia present with various alterations of the gut microbiota and increased intestinal permeability. In addition, the hypothalamic-pituitary-adrenal (HPA) axis dysregulation and subclinical inflammation have been reported in this group of patients. Although it has been found that the HPA axis dysregulation appears as a consequence of psychosocial stress, especially traumatic life events, the exact mechanisms of this observation remain unclear. Animal model studies have unraveled several mechanisms linking the gut microbiota with the HPA axis dysfunction. Indeed, the gut microbiota can activate the HPA axis through several mediators that cross the blood-brain barrier and include microbial antigens, cytokines and prostaglandins. There is also evidence that various microbial species can affect ileal corticosterone production that may impact the activity of the HPA axis. However, some metabolites released by various microbes, e.g., short-chain fatty acids, can attenuate the HPA axis response. Moreover, several bacteria release neurotransmitters that can directly interact with vagal afferents. It has been postulated that the HPA axis activation can impact the gut microbiota and intestinal permeability. In this article, we discuss various mechanisms linking the gut microbiota with the HPA axis activity and summarize current evidence for a cross-talk between the gut-brain axis and the HPA axis from studies of patients with mood and psychotic disorders. Finally, we show potential clinical implications that can arise from future studies investigating the HPA axis activity with respect to the gut microbiota in severe mental disorders.

Short chain fatty acids (SCFAs) being produced during fermentation of non-digestible polysaccharides are regulatory compounds with the potential to influence inflammatory, as well as emotional state and cognition through the gut&ndash, brain axis. We analyzed the association between stool concentration of SCFAs (acetic acid (C 2:0), propionic acid (C 3:0), isobutyric acid (C 4:0 i), butyric acid (C 4:0 n), isovaleric acid (C 5:0 i) valeric acid (C 5:0 n), isocaproic acid (C 6:0 i), caproic acid, and (C 6:0 n) heptanoic acid (C 7:0)) and depressive symptoms among women and looked for the potential confounders of microbiota byproduct synthesis. We enrolled 116 women aged 52.0 &plusmn, 4.7 years and recognized depression in 47 (40.52%). To analyze the emotional state, Beck&rsquo, s Depression Inventory (BDI) was used. We assessed SCFAs content by means of gas chromatography. Fiber intake was estimated using parts of food frequency questionnaire. The content of acetic acid was significantly lowered compared to non-depressed women (median {IQR}: 29.49 {20.81} vs. 34.99 {19.55}, p = 0.04). A tendency toward decreased level of propionic acid was noticed (median {IQR}: 16.88 {9.73} vs. 21.64 {12.17}, p = 0.07), while the concentration of isocaproic acid was significantly increased in (median {IQR}: 0.89 {1.15} vs. 0.56 {0.95}, p &lt, 0.01) comparison to matched healthy subjects. We found negative correlations between acetate, propionate, and Beck&rsquo, s score (r = &minus, 0.2, p = 0.03, r = &minus, 0.21, p = 0.02, respectively). Statistically significant correlations between acetate and propionate and BDI somatic score (r = &minus, 0.21, p = 0.01, 0.17, p = 0.03), as well as correlations regarding isocaproic and both cognitive/affective (r = 0.37, p = 0.0001) and somatic (r = 9.37, p &lt, 0.001) scores were found. Women who declared current usage of lipid-lowering and thyroid drugs in the past, had higher content of C6:0-i (Users, median {IQR}: 1.91 {3.62} vs. non-users, 0.55 {0.67}, p = 0.0048).and lower of C2:0 (Users, median {IQR}: 23.07 {12.80} vs. non users 33.73 {21.44}, p = 0.041), respectively. No correlations regarding SCFAs concentration and fiber intake were found. We concluded that SCFAs may potentially contribute to depression phenotype, however, due to the small size of groups suffering from moderately heavy (n = 5) and severe (n = 7) depression, the conclusion should be treated with caution. Pharmacotherapy of hyperlipidemia and thyroid disease might affect SCFAs synthesis. Studies with more participants are required.

Obesity in the postmenopausal period is associated with an increased risk of cardiovascular diseases in women. One of the key drivers of cardiovascular risk is endothelial dysfunction, thus, this is also a crucial point for studies on new therapeutic methods of cardioprotective properties. The aim of the current study was to evaluate the effect of two doses of multispecies probiotic Ecologic&reg, Barrier supplement on functional (primary endpoint) and biochemical parameters (secondary endpoint) of endothelial dysfunction in obese postmenopausal women in a 12-week randomized, placebo-controlled clinical trial. A total of 81 obese Caucasian women participated in the trial. The subjects were randomly assigned to three groups that received a placebo, a low dose (LD) (2.5 &times, 109 colony forming units (CFU) per day), or a high dose (HD) (1 &times, 1010 CFU per day) of lyophilisate powder containing live multispecies probiotic bacteria. The probiotic supplement was administered each day for 12 weeks in two equal portions. A high dose probiotic supplementation for 12 weeks decreased systolic blood pressure, vascular endothelial growth factor, pulse wave analysis systolic pressure, pulse wave analysis pulse pressure, pulse wave analysis augmentation index, pulse wave velocity, interleukin-6, tumor necrosis factor alpha, and thrombomodulin. Low doses of probiotic supplementation decreased the systolic blood pressure and interleukin-6 levels. The mean changes in the estimated parameters, compared among the three groups, revealed significant differences in the vascular endothelial growth factor, the pulse wave analysis systolic pressure, the pulse wave analysis augmentation index, the pulse wave velocity, the tumor necrosis factor alpha, and thrombomodulin. The post hoc tests showed significant differences for all parameters between HD and the placebo group, and HD and LD (besides pulse wave analysis augmentation index). We show for the first time that supplementation with multispecies probiotic Ecologic&reg, Barrier favorably modifies both functional and biochemical markers of vascular dysfunction in obese postmenopausal women.

Rationale Multiple drugs are known to induce metabolic malfunctions, among them second-generation antipsychotics (SGAs). The pathogenesis of such adverse effects is of multifactorial origin. Objectives We investigated whether SGAs drive dysbiosis, assessed whether gut microbiota alterations affect body weight and metabolic outcomes, and looked for the possible mechanism of metabolic disturbances secondary to SGA treatment in animal and human studies. Methods A systematic literature search (PubMed/Medline/Embase/ClinicalTrials.gov/PsychInfo) was conducted from database inception until 03 July 2018 for studies that reported the microbiome and weight alterations in SGA-treated subjects. Results Seven articles reporting studies in mice (experiments = 8) and rats (experiments = 3) were included. Olanzapine was used in five and risperidone in six experiments. Only three articles (experiments = 4) in humans fit our criteria of using risperidone and mixed SGAs. The results confirmed microbiome alterations directly (rodent experiments = 5, human experiments = 4) or indirectly (rodent experiments = 4) with predominantly increased Firmicutes abundance relative to Bacteroidetes, as well as weight gain in rodents (experiments = 8) and humans (experiments = 4). Additionally, olanzapine administration was found to induce both metabolic alterations (adiposity, lipogenesis, plasma free fatty acid, and acetate levels increase) (experiments = 3) and inflammation (experiments = 2) in rodents, whereas risperidone suppressed the resting metabolic rate in rodents (experiments = 5) and elevated fasting blood glucose, triglycerides, LDL, hs-CRP, antioxidant superoxide dismutase, and HOMA-IR in humans (experiment = 1). One rodent study suggested a gender-dependent effect of dysbiosis on body weight. Conclusions Antipsychotic treatment-related microbiome alterations potentially result in body weight gain and metabolic disturbances. Inflammation and resting metabolic rate suppression seem to play crucial roles in the development of metabolic disorders. Electronic supplementary material The online version of this article (10.1007/s00213-018-5102-6) contains supplementary material, which is available to authorized users.

During the postmenopausal period, the risk of cardiovascular diseases is increased in many obese women and is associated with a worse cardiometabolic profile and a sub-chronic low-grade systemic inflammation caused by a gut barrier permeability dysfunction. Here, we tested whether administration of two different dosages of the multispecies probiotic Ecologic&reg, Barrier influenced the cardiometabolic biochemical parameters and lipopolysaccharide levels, the latter used as a marker of increased gut permeability in obese postmenopausal women. A total of 81 obese Caucasian postmenopausal women participated in the trial. The subjects were randomly assigned to three groups that received a placebo, a low dose (LD) (2.5 &times, 109 colony forming units (CFU) per day), or a high dose (HD) (1 &times, 1010 CFU per day) of lyophilisate powder containing live multispecies probiotic bacteria. The probiotic supplement was administered each day in two equal portions for 12 weeks. We found significant (p &lt, 0.05) favorable changes (mostly large or medium effects) in the evaluated parameters in both the HD and LD groups but not in the placebo group. In the HD group, lipopolysaccharide, waist, fat mass, subcutaneous fat, uric acid, total cholesterol, triglycerides, low-density lipoprotein cholesterol, glucose, insulin, and insulin-resistant index (HOMA-IR) were improved. Similar changes were observed in the LD group, except for lipopolysaccharide, uric acid, triglycerides, and glucose levels. Additionally, significant differences were observed in both groups in terms of fat percentage and visceral fat. When the mean changes were compared between the three groups, statistically significant differences in lipopolysaccharide levels, uric acid, glucose, insulin, and HOMA-IR were found. Post hoc tests revealed significant differences in the mean changes (mostly medium effects) between the HD and LD groups for uric acid, glucose, insulin, and HOMA-IR. In the 12-week randomized, placebo-controlled, double-blind intervention, we observed that supplementation with the multispecies probiotic Ecologic&reg, Barrier favorably affected the risk factors in a dose-dependent manner, showing beneficial effects on the cardiometabolic parameters and gut permeability of the patients. Our results suggest that this product can be effective in the prevention and treatment of cardiovascular diseases in obese postmenopausal women.

Inflammatory bowel disease (IBD) is an umbrella term for Crohn’s disease (CD) and ulcerative colitis (UC). In light of evolving epidemiology of CD, its clinical management is still complex and remains a challenge for contemporary physicians. With the advent of new diagnostic and treatment paradigms, there is a growing need for new biomarkers to guide decision-making, differential diagnosis, disease activity monitoring, as well as prognosis. However, both clinical and endoscopic scoring systems, widely utilized for disease monitoring and prognosis, have drawbacks and limitations. In recent years, biochemical peptides have become available for IBD monitoring and more frequently used as surrogate markers of gut inflammation. Emerging concepts that revolve around molecular, stem cell, epigenetic, microbial or metabolomic pathways associated with vascular and epithelial gut barrier could lead to development of new CD biomarkers. Measurement of cell-derived microvesicles (MVs) in the blood of IBD patients is another emerging concept helpful in future disease management. In this review, we discuss novel concepts of non-invasive biomarkers, which may become useful in monitoring of CD activity and prognosis. We discuss metabolomics as a new powerful tool for clinicians to guide differential IBD diagnosis. In the coming years, new developments of prognostic tools are expected, aiming for breakthroughs in the management of patients with CD.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) are among the most frequently prescribed groups of drugs worldwide. The use of NSAIDs is associated with a high number of significant adverse effects. Recently, the safety of PPIs has also been challenged. Capsule endoscopy studies reveal that even low-dose NSAIDs are responsible for gut mucosal injury and numerous clinical adverse effects, for example, bleeding and anemia, that might be difficult to diagnose. The frequent use of PPIs can exacerbate NSAID-induced small intestinal injury by altering intestinal microbiota. Thus, the use of PPI is considered to be an independent risk factor associated with NSAID-associated enteropathy. In this review, we discuss this important clinical problem and review relevant aspects of epidemiology, pathophysiology, and management. We also present the hypothesis that even minor and subclinical injury to the intestinal mucosa can result in significant, though delayed, metabolic consequences, which may seriously affect the health of an individual. PubMed was searched using the following key words (each key word alone and in combination): gut microbiota, microbiome, non-steroidal anti inflammatory drugs, proton pump inhibitors, enteropathy, probiotic, antibiotic, mucosal injury, enteroscopy, and capsule endoscopy. Google engine search was also carried out to identify additional relevant articles. Both original and review articles published in English were reviewed.

Kidney injury in chronic kidney disease (CKD) is likely multifactorial, but recent data support that a component is mediated by mechanisms used by the kidney to increase acidification in response to an acid challenge to systemic acid–base status. If so, systemic alkalization might attenuate this acid-induced component of kidney injury. An acid challenge to systemic acid–base status increases nephron acidification through increased production of endothelin, aldosterone, and angiotensin II, each of which can contribute to kidney inflammation and fibrosis that characterizes CKD. Systemic alkalization that ameliorates an acid challenge might attenuate the contributions of angiotensin II, endothelin, and aldosterone to kidney injury. Some small clinical studies support the efficacy of alkalization in attenuating kidney injury and slowing glomerular filtration rate decline in CKD. This review focuses on the potential that orally administered NaHCO 3 prevents CKD progression and additionally addresses its mechanism of action, side effects, possible complications, dosage, interaction, galenic form description, and contraindications. Current National Kidney Foundation guidelines recommend oral alkali, including NaHCO 3 - , in CKD patients with serum HCO 3 - 3 will be the focus of this review because of its relative safety and apparent efficacy, and its comparatively low cost.

Accumulating evidence indicates the potential effect of microbiota on the pathogenesis and course of schizophrenia. However, the effects of olanzapine, second-generation antipsychotics, on gut microbiota have not been investigated in humans. This study aimed to analyze fecal microbiota in schizophrenia patients treated with olanzapine during six weeks of their hospital stay. After a seven-day washout from all psychotropic medications, microbiota compositions were evaluated at baseline and after six weeks of hospitalization using 16S rRNA sequencing. The study was conducted in 20 inpatients, who followed the same hospital routine and received 5&ndash, 20 mg daily doses of olanzapine. Olanzapine treatment was associated with clinical improvements in all patients and significant increases in body mass index in females, but not changes in gut microbiota compositions and predicted function. The severity of symptoms at the beginning of treatment varied in accordance with the predicted metabolic activity of the bacteria. The present findings indicate that the microbiota of schizophrenia patients is highly individual and has different taxonomical (Type 1, with a predominance of Prevotella, and Type 2 with a higher abundance of Bacteroides, Blautia and Clostridium) and functional clusters, and it does not change following six weeks of olanzapine therapy, in addition, the microbiota is not associated with either the weight gain observed in women or the effectiveness of olanzapine therapy.

Obesity has become an emerging global issue responsible for an increased risk of cardiovascular diseases and cancer. Gut microbiota is one of biological factors involved in the pathogenesis of obesity and metabolic disorders. Microbiome alteration has been associated with chronic endotoxemia and microinflammation, insulin resistance and hyperinsulinemia – factors playing an important role in the development of metabolic disorders such as non-alcoholic steatohepatitis (NASH), diabetes mellitus (DM) and dyslipidemia. Bariatric interventions are an important part of obesity treatment. Surgical interventions are the most effective procedures. Endoscopy assisted techniques (intragastric balloon or duodenal-endoluminal sleeve) are also very promising, clinically tested procedures. Dietary interventions changing gut microbiota are more frequently used. However, our knowledge about the mechanisms of weight loss triggered by these interventions is incomplete. Recent experimental and clinical studies provide novel data that bariatric surgery modulates intestinal microbiome and changes its potential of energy harvest in the gut. Surgically altered microbiota in the short term exert profound but beneficial metabolic effects in humans. However, long-term consequences of such modulation are unknown. Recent data from randomized clinical trials support the notion that dietary interventions and supplementation of pre- and probiotics favorably modulate gut microbiota and augment weight loss after bariatric procedures.

Intestinal microbiota play an important role in the pathogenesis of surgical site infections (SSIs) and other surgery-related complications (SRCs). Probiotics and synbiotics were found to lower the risk of surgical infections and other surgery-related adverse events. We systematically reviewed the approach based on the administration of probiotics and synbiotics to diminish SSIs/SRCs rates in patients undergoing various surgical treatments and to determine the mechanisms responsible for their effectiveness. A systematic literature search in PubMed/MEDLINE/Cochrane Central Register of Controlled Trials from the inception of databases to June 2018 for trials in patients undergoing surgery supplemented with pre/pro/synbiotics and randomized to the intervention versus placebo/no treatment and reporting on primarily: (i) putative mechanisms of probiotic/symbiotic action, and secondarily (ii) SSIs and SRCs outcomes. Random-effect model meta-analysis and meta-regression analysis of outcomes was done. Thirty-five trials comprising 3028 adult patients were included, interventions were probiotics (n = 16) and synbiotics (n = 19 trials). We found that C-reactive protein (CRP) and Interleukin-6 (IL-6) were significantly decreased (SMD: &minus, 0.40, 95% CI [&minus, 0.79, &minus, 0.02], p = 0.041, SMD: &minus, 0.41, 95% CI [&minus, 0.70, &minus, 0.02], p = 0.006, respectively) while concentration of acetic, butyric, and propionic acids were elevated in patients supplemented with probiotics (SMD: 1.78, 95% CI [0.80, 2.76], p = 0.0004, SMD: 0.67, 95% CI [0.37, &minus, 0.97], p = 0.00001, SMD: 0.46, 95% CI [0.18, 0.73], p = 0.001, respectively). Meta-analysis confirmed that pro- and synbiotics supplementation was associated with significant reduction in the incidence of SRCs including abdominal distention, diarrhea, pneumonia, sepsis, surgery site infection (including superficial incisional), and urinary tract infection, as well as the duration of antibiotic therapy, duration of postoperative pyrexia, time of fluid introduction, solid diet, and duration of hospital stay (p &lt, 0.05). Probiotics and synbiotics administration counteract SSIs/SRCs via modulating gut-immune response and production of short chain fatty acids.

IntroductionNovel research concepts based on therapies aiming to modulate intestinal microbiota are emerging. The evidence is mounting that gut-brain axis plays an important role in the development of mood and depressive disorders [1]. The similarities between blood brain barrier (BBB) and gut vascular barrier (GVB) and their role in chronic diseases have been recently unraveled [2]. Especially convincing data come from animal models, where administration of probiotics and antibiotics in germ and pathogen free mice showed beneficial role in the regulation of behavior, cognition, pain, anxiety and mood.Aims and resultsBased on available data as well as on studies looking at the effect of multispecies probiotics (Ecologic® Barrier containing B.bifidumW23, B.lactisW52, L.acidophilusW37, L.brevisW63, L.caseiW56, L.salivariusW24, L.lactisW19, L.lactisW58) on cognitive reactivity to sad mood in healthy volunteers [3] we designed the human trial aiming to compare microbiome alterations and response to therapy in patients with depression and schizophrenia. Moreover, in vitro and in vivo data support the notion that multispecies probiotics are capable of improving gut barrier function [4] and may alleviate disorders affecting mood and depressive-like behavior. We postulate that therapies modulating the microbiome-gut-brain axis warrant further investigations.ConclusionMultispecies probiotics have the potential to influence the gut-brain axis and alleviate mental disorders. Ongoing clinical study in patients with depression and schizophrenia will help to further unravel the role of gut-brain axis in the treatment of patients with psychiatric disturbances.Disclosure of interestThe authors have not supplied their declaration of competing interest.