Current Clinical Pharmacology - Volume 15, Issue 3, 2020

Inflammatory bowel diseases, namely Crohn's disease and ulcerative colitis, are currently considered multifactorial pathologies in which various combined environmental factors act on genetic background, giving rise to chronic inflammation of the gastrointestinal tract. Ulcerative colitis is an inflammation of the colon caused by a dysregulated immune response to host intestinal microbiota in genetically susceptible subjects. Ulcerative colitis has a strong impact on patients' quality of life, as well as high costs for the health-care system. A great interest on the role of intestinal microbiota modulation in ulcerative colitis is emerging. Several studies have shown an improvement of inflammatory markers and symptoms in ulcerative colitis patients through treatments with probiotics and prebiotics separately. Despite the low number of studies on the treatment of ulcerative colitis by specific strains of probiotics plus selected prebiotics, i.e. synbiotics, the results are promising, even if discordant. The mechanism of action in synbiotics supplementation is still unclear and needs more investigation, although there is a large number of data indicating that the synergism between probiotics and prebiotics favours the survival and implantation of probiotics into the gastrointestinal tract with beneficial effects on human health by modulating the inflammatory response and gut microbiota composition. The aim of this minireview is to describe the main in vitro, animal and human studies performed up to now, that have used synbiotics to treat ulcerative colitis, and to highlight limitations and future perspectives.

Globally, the population over the age of 60 is growing fast, but people age in different ways. Frailty, shown by the accumulation of age-related deficits, is a state of increased vulnerability to adverse outcomes among people of the same chronological age. Ageing results in a decline in diversity and homeostasis of microbiomes, and gut flora changes are related to health deficit accumulation and adverse health outcomes. In older people, health deficits including inappropriate intake, sarcopenia, physical inactivity, polypharmacy, and social vulnerability are factors associated with gut dysbiosis. The use of probiotics and prebiotics is a cost-effective and widely available intervention. Intake of probiotics and prebiotics may improve the homeostasis of gut microflora and prevent frailty and unhealthy aging. However, health effects vary among probiotics and prebiotics and among individual populations. This narrative review summarizes recent evidence about the relationship between prebiotic and probiotic consumption with health outcomes in older people.

Background: Chronic wounds are commonly associated with polymicrobial biofilm infections. In the last years, the extensive use of antibiotics has generated several antibiotic-resistant variants. To overcome this issue, alternative natural treatments have been proposed, including the use of microorganisms like probiotics. The aim of this manuscript was to review current literature concerning the application of probiotics for the treatment of infected chronic wounds. Methods: Relevant articles were searched in the Medline database using PubMed and Scholar, using the keywords “probiotics” and “wound” and “injuries”, “probiotics” and “wound” and “ulcer”, “biofilm” and “probiotics” and “wound”, “biofilm” and “ulcer” and “probiotics”, “biofilm” and “ulcer” and “probiotics”, “probiotics” and “wound”. Results: The research initially included 253 articles. After removal of duplicate studies, and selection according to specific inclusion and exclusion criteria, 19 research articles were included and reviewed, accounting for 12 in vitro, 8 in vivo studies and 2 human studies (three articles dealing with animal experiments included also in vitro testing). Most of the published studies about the effects of probiotics for the treatment of infected chronic wounds reported a partial inhibition of microbial growth, biofilm formation and quorum sensing. Discussion: The application of probiotics represents an intriguing option in the treatment of infected chronic wounds with multidrug-resistant bacteria; however, current results are difficult to compare due to the heterogeneity in methodology, laboratory techniques, and applied clinical protocols. Lactobacillus plantarum currently represents the most studied strain, showing a positive application in burns compared to guideline treatments, and an additional mean in chronic wound infections. Conclusions: Although preliminary evidence supports the use of specific strains of probiotics in certain clinical settings such as infected chronic wounds, large, long-term clinical trials are still lacking, and further research is needed.

Constipation is a highly prevalent functional gastrointestinal disorder that may significantly affect the quality of life and health care costs. Treatment for constipation has been broadly reviewed by cognitive therapies, medications, and surgical interventions. Gut microbiota such as Bifidobacterium, Clostridium, Bacteroidetes, and Lactobacilli have been demonstrated in functional gastrointestinal disorders and prebiotics to play a role in augmenting their presence. Prebiotics are ingredients in foods that remain undigested, stimulating the bacteria. There are a variety of prebiotics; however, there exists only a handful of studies that describe their efficacy for chronic constipation. The purpose of this study is to review the available literature on the utility of different commercially available prebiotics in patients with functional and chronic idiopathic constipation. To fulfil the objectives of the study, published articles in the English language on databases such as Pubmed, Ovid Medline, and EMBASE were searched. The terms prebiotics, constipation, chronic constipation, functional constipation were used. We reviewed and included 21 randomized controlled trials exploring the role of prebiotics in constipated adults. Prebiotics are effective treatments for chronic idiopathic constipation and showed improvement in the stool consistency, number of bowel moments and bloating. Although which prebiotic formulary would promote improved symptoms of constipation is still not clear.

The incidence, prevalence, and cost of care associated with diagnosis and management of inflammatory bowel disease are on the rise. The role of gut microbiota in the causation of Crohn's disease and ulcerative colitis has not been established yet. Nevertheless, several animal models and human studies point towards the association. Targeting intestinal dysbiosis for remission induction, maintenance, and relapse prevention is an attractive treatment approach with minimal adverse effects. However, the data is still conflicting. The purpose of this article is to provide the most comprehensive and updated review on the utility of prebiotics and probiotics in the management of active Crohn's disease and ulcerative colitis/pouchitis and their role in the remission induction, maintenance, and relapse prevention. A thorough literature review was performed on PubMed, Ovid Medline, and EMBASE using the terms “prebiotics AND ulcerative colitis”, “probiotics AND ulcerative colitis”, “prebiotics AND Crohn's disease”, “probiotics AND Crohn's disease”, “probiotics AND acute pouchitis”, “probiotics AND chronic pouchitis” and “prebiotics AND pouchitis”. Observational studies and clinical trials conducted on humans and published in the English language were included. A total of 71 clinical trials evaluating the utility of prebiotics and probiotics in the management of inflammatory bowel disease were reviewed and the findings were summarized. Most of these studies on probiotics evaluated lactobacillus, De Simone Formulation or Escherichia coli Nissle 1917 and there is some evidence supporting these agents for induction and maintenance of remission in ulcerative colitis and prevention of pouchitis relapse with minimal adverse effects. The efficacy of prebiotics such as fructooligosaccharides and Plantago ovata seeds in ulcerative colitis are inconclusive and the data regarding the utility of prebiotics in pouchitis is limited. The results of the clinical trials for remission induction and maintenance in active Crohn's disease or post-operative relapse with probiotics and prebiotics are inadequate and not very convincing. Prebiotics and probiotics are safe, effective and have great therapeutic potential. However, better designed clinical trials in the multicenter setting with a large sample and long duration of intervention are needed to identify the specific strain or combination of probiotics and prebiotics which will be more beneficial and effective in patients with inflammatory bowel disease.

Background: Diabetic Nephropathy is a frequent complication of diabetes mellitus due to functional and structural modifications in multiple kidney compartments. Probiotics have risen lately as a forthcoming therapeutic intervention but they have not been systematically evaluated in diabetic nephropathy so far. The aim of this systematic review was to evaluate randomized controlled trials and experimental studies assessing the effect of probiotic supplements on diabetic nephropathy. Methods: An extensive literature search was conducted through electronic databases (PubMed, Scopus, Cinahl and Medline) with the Medical Subject Headings and entry terms of “diabetic nephropathy”, “diabetic renal disease” and “probiotics”. The search yielded 116 results, 9 of which met the inclusion criteria for this systematic review. Results: Most of the microorganisms used in the studies belonged to the Lactobacillus and Bifidobacterium genus. The dosage ranged from 2x10⁷ to 6x10¹⁰ CFU/ g. The form of the probiotics varied across the studies (capsules, sachets, soy milk, kefir and honey). The majority of the studies demonstrated the benefits of probiotic supplementation on the reduction of inflammation, oxidative stress and on the amelioration of renal function biomarkers in subjects with diabetic nephropathy. No major gastrointestinal adverse events were observed during the intervention time with probiotics. Conclusion: Findings of this systematic review demonstrate the positive impact of probiotics on Diabetic Nephropathy without any major adverse events. Moreover, future larger randomized controlled trials with bigger samples and longer follow-up time are deemed necessary for further valid results on the effectiveness of probiotic supplementation on Diabetic Nephropathy.

Background: Poor adherence to the prescribed therapy leads to low bone mineral density and enhance the development of osteoporosis complications and unnecessary hospitalization. Objective: To explore factors associated with medication non-adherence in patients with osteoporosis. Findings would help guide the development of future pharmaceutical care interventions aim at improving health outcomes for patients with osteoporosis. Methods: The study was conducted at an outpatient osteoporosis clinic at the Royal Medical Services Hospital. Variables including socio-demographics and medical factors were collected using medical records and custom-designed questionnaire. Medication adherence was assessed using the validated 4-item Morisky Medication Adherence Scale. Logistic regression was performed to develop a model with variables that best predicted medication non-adherence in patients with osteoporosis in Jordan. Results: A total of 296 patients participated in the study. Most of the study participants (72.3%) were found non-adherent. Patients were found less likely to adhere to the prescribed medications with each unit increase in the number of prescribed medications (OR = 2.503, CI = 1.103-5.680) and if they did not have a trust in the efficacy of the medications (OR = 5.544, CI = 0.990-31.058). Conclusion: Medication adherence for patients with osteoporosis has considered scope for improvement in Jordan. Simplifying dosage regimen in addition to taking patients’ preferences when selecting the medications should be taken into account in future interventions designed to improve health outcomes for patients with osteoporosis.

Aim: Endogenous agmatine has a significant role in learning and memory processes as a neurotransmitter. Various studies described the physiological role of endogenous agmatine in learning and memory of multiple cognitive tasks suggesting elevated levels of agmatine during the learning process in the rat brain. Dietary intake of choline showed correlation with cognitive functions in human subjects and treatment with choline supplements validated the ability to diminish learning and cognitive impairment dementias. Methods: 36 Albino rats were equally divided into three groups previously: a) control-water, b) Test I - AlCl3 (100 mg/Kg body weight), and c) Test II - Forced swim stress (FSS) for 14 days. On the next day of AlCl3 and FSS last administration, animals were allocated into further three groups and received the following treatments: a. water was given orally to the control group, b. Agmatine (100 mg/Kg Body Weight) group, and c. Choline (100 mg/Kg Body Weight) group for the next 14 days. Behaviors were assessed in Light/Dark Box, Open Field, Novel Object Recognition Test (NOR), T Maze Test, and Morris Water Maze Test. Results: Animals administered with agmatine demonstrated increased time spent in bright areas of light/dark box and square crossed while improved spatial memory in Morris water maze and T maze test and enhanced discrimination of novel object in NOR were observed in learning and memory paradigms along with choline. Conclusion: The present study determines that agmatine at the dose of (100 mg/kg body weight) attenuates memory and cognitive impairment in comparison with choline supplements.