Non-gastrointestinal Diseases Research Articles

Association between Helicobacter pylori Infection and Iron Deficiency in Sudanese Population in Khartoum State

Background: Helicobacter pylori infection is a major gastric infection worldwide and has been associated with many gastrointestinal and non-gastrointestinal diseases including hematological disorders. Objective: Aimed to study the association between H. pylori infection and iron deficiency among Sudanese population. Materials and Methods: This is analytical case control study, conducted in Sudan, Khartoum state in Omdurman locality, during the period from May 2018 to April 2019. Include 100 samples, the stool and blood samples were collected from 100 Sudanese subjects (50 were infected with H. pylori as cases and 50 were apparently healthy subjects as controls). Stool samples were tested for H. pylori Ag by commercially available kits (HanzouAllTest Biotech Co., Ltd, Germany), all blood samples were analyzed for complete blood count using (SYSMEX KX21N) automated analyzer and serum iron profile (iron, ferritin, and TIBC) using spectrophotometery and turbidimetry. The obtained results is analyzed by SPSS versions 16.0, significant level was set at p-value equal or less than 0.05 and the results were presented in form of tables and figures. Results: The results of H. pylori antigen were positive in all cases and negative in control samples. Serum iron level mean was significantly lower among H. pylori positive patient (62±18.1) than control group (91.3±16.7) (p-value 0.001), serum ferritin level mean was significantly lower in H. pylori infected patients (36.8±16.5) than control group (64±16.4) (p-value 0.003), hemoglobin level mean was significantly lower in H. pylori patients (12.5 ±1.1) than control group (13.8±1.0) (p-value 0.009), PCV level mean was lower in H. pylori patients (37.6±3.1) than control group (41±3.0) (p-value .036), TIBC mean was 313 in cases and 308 in control samples. All other parameters showed no significant difference between H. pylori positive patients and control subjects. Conclusion: This study concluded that H. pylori infection is lead to iron deficiency in Sudanese patients.

Gut-liver axis: Potential mechanisms of action of food-derived extracellular vesicles.

Food-derived extracellular vesicles (FEVs) are nanoscale membrane vesicles obtained from dietary materials such as breast milk, plants and probiotics. Distinct from other EVs, FEVs can survive the harsh degrading conditions in the gastrointestinal tract and reach the intestines. This unique feature allows FEVs to be promising prebiotics in health and oral nanomedicine for gut disorders, such as inflammatory bowel disease. Interestingly, therapeutic effects of FEVs have recently also been observed in non-gastrointestinal diseases. However, the mechanisms remain unclear or even mysterious. It is speculated that orally administered FEVs could enter the bloodstream, reach remote organs, and thus exert therapeutic effects therein. However, emerging evidence suggests that the amount of FEVs reaching organs beyond the gastrointestinal tract is marginal and may be insufficient to account for the significant therapeutic effects achieved regarding diseases involving remote organs such as the liver. Thus, we herein propose that FEVs primarily act locally in the intestine by modulating intestinal microenvironments such as barrier integrity and microbiota, thereby eliciting therapeutic impact remotely on the liver in non-gastrointestinal diseases via the gut-liver axis. Likewise, drugs delivered to the gastrointestinal system through FEVs may act via the gut-liver axis. As the liver is the main metabolic hub, the intestinal microenvironment may be implicated in other metabolic diseases. In fact, many patients with non-alcoholic fatty liver disease, obesity, diabetes and cardiovascular disease suffer from a leaky gut and dysbiosis. In this review, we provide an overview of the recent progress in FEVs and discuss their biomedical applications as therapeutic agents and drug delivery systems, highlighting the pivotal role of the gut-liver axis in the mechanisms of action of FEVs for the treatment of gut disorders and metabolic diseases.

The Interplay between Helicobacter pylori and Gut Microbiota in Non-Gastrointestinal Disorders: A Special Focus on Atherosclerosis.

The discovery of Helicobacter pylori (H. pylori) in the early 1980s by Nobel Prize winners in medicine Robin Warren and Barry Marshall led to a revolution in physiopathology and consequently in the treatment of peptic ulcer disease. Subsequently, H. pylori has also been linked to non-gastrointestinal diseases, such as autoimmune thrombocytopenia, acne rosacea, and Raynaud's syndrome. In addition, several studies have shown an association with cardiovascular disease and atherosclerosis. Our narrative review aims to investigate the connection between H. pylori infection, gut microbiota, and extra-gastric diseases, with a particular emphasis on atherosclerosis. We conducted an extensive search on PubMed, Google Scholar, and Scopus, using the keywords "H. pylori", "dysbiosis", "microbiota", "atherosclerosis", "cardiovascular disease" in the last ten years. Atherosclerosis is a complex condition in which the arteries thicken or harden due to plaque deposits in the inner lining of an artery and is associated with several cardiovascular diseases. Recent research has highlighted the role of the microbiota in the pathogenesis of this group of diseases. H. pylori is able to both directly influence the onset of atherosclerosis and negatively modulate the microbiota. H. pylori is an important factor in promoting atherosclerosis. Progress is being made in understanding the underlying mechanisms, which could open the way to interesting new therapeutic perspectives.

<i>Helicobacter Pylori</i> infection and non-alcoholic fatty liver disease. Is there a relationship?

The most prevalent infection that causes chronic gastritis, gastric ulcers, and gastric cancer is Helicobacter pylori infection. Recent research has implicated H. pylori in the pathogenesis of non-gastrointestinal diseases such as cardiovascular, autoimmune, and metabolic disorders. In addition, since H. pylori is believed to be implicated in insulin resistance, numerous studies have been conducted to determine the relationship between H. pylori infection and nonalcoholic fatty liver diseases (NAFLD), but the results have been contested. The purpose of this study is to determine the relationship between H. Pylori infection and nonalcoholic fatty liver diseases. One hundred patients were examined via urea breath test for the presence of H. pylori infection and vibration-controlled transient elastography for the diagnosis of non-alcoholic fatty liver disease. After adjusting for other variables, age, body mass index (BMI), and H. pylori infection were associated with elastography 248dB/m. Infection with H. pylori contributes to the development of NAFLD, and its eradication may influence prognosis.

Fecal and Circulating Biomarkers for the Non-Invasive Assessment of Intestinal Permeability.

The study of intestinal permeability is gaining growing interest due to its relevance in the onset and progression of several gastrointestinal and non-gastrointestinal diseases. Though the involvement of impaired intestinal permeability in the pathophysiology of such diseases is recognized, there is currently a need to identify non-invasive biomarkers or tools that are able to accurately detect alterations in intestinal barrier integrity. On the one hand, promising results have been reported for novel in vivo methods based on paracellular probes, i.e., methods that can directly assess paracellular permeability and, on the other hand, on fecal and circulating biomarkers able to indirectly assess epithelial barrier integrity and functionality. In this review, we aimed to summarize the current knowledge on the intestinal barrier and epithelial transport pathways and to provide an overview of the methods already available or currently under investigation for the measurement of intestinal permeability.

Fusobacterium nucleatum, a key pathogenic factor and microbial biomarker for colorectal cancer.

Colorectal cancer (CRC), one of the most prevalent cancers, has complex etiology. The dysbiosis of intestinal bacteria has been highlighted as an important contributor to CRC. Fusobacterium nucleatum, an oral anaerobic opportunistic pathogen, is enriched in both stools and tumor tissues of patients with CRC. Therefore, F. nucleatum is considered to be a risk factor for CRC. This review summarizes the biological characteristics and the mechanisms underlying the regulatory behavior of F. nucleatum in the tumorigenesis and progression of CRC. F. nucleatum as a marker for the early warning and prognostic prediction of CRC, and as a target for prevention and treatment, is also described.

Therapeutic eradication choices in Helicobacter pylori infection in children.

Current recommendations on Helicobacter pylori (H. pylori) eradication in children differ from adults. In H. pylori-infected adults, the eradication is always recommended because of the risk to develop gastrointestinal and non-gastrointestinal associated diseases. Instead, before treating infected children, we should consider all the possible causes and not merely focus on H. pylori infection. Indeed, pediatric international guidelines do not recommend the test and treat strategy in children. Therefore, gastroscopy with antimicrobial susceptibility testing by culture on gastric biopsies should be performed before starting the eradication therapy in children to better evaluate all the possible causes of the symptomatology and to increase the eradication rate. Whether antibiotic susceptibility testing is not available, gastroscopy is anyway recommended to better set any possible cause of symptoms and not simply focus on the presence of H. pylori. In children the lower antibiotics availability compared to adults forces to treat based on antimicrobial susceptibility testing to minimize the unsuccessful rates. The main antibiotics used in children are amoxicillin, clarithromycin, and metronidazole in various combinations. In empirical treatment, triple therapy for 14 days based either on local antimicrobial susceptibility or on personal antibiotic history is generally recommended. Triple therapy with high dose of amoxicillin is a valid alternative choice, either in double resistance or in second-line treatment. Moving from therapeutic regimens used in adults, we could also select quadruple therapy with or without bismuth salts. However, all the treatment regimens often entail unpleasant side effects and lower compliance in children. In this review, the alternative and not yet commonly used therapeutic choices in children were also analyzed.

Bacillus cereus cytotoxin K triggers gasdermin D-dependent pyroptosis

Bacillus cereus is well known as a causative agent of foodborne gastrointestinal diseases and systemic non-gastrointestinal diseases. We have recently identified a pathogenic B. cereus (named H2) from a deep-sea cold-seep. H2 possesses the pyroptosis-inducing capacity and contains a number of enterotoxins including cytotoxin K (CytK). In the present work, we examined the cytotoxicity of the CytK of H2 to human macrophages. CytK bound macrophages by interaction with the plasma membrane and caused cellular structure damage. CytK−cell interaction triggered rapid pyroptosis mediated by caspase 1-activated gasdermin D (GSDMD). CytK-induced pyroptosis required NLRP3 inflammasome activation, K+ efflux, and intracellular Ca2+ accumulation. CytK exhibited apparent binding to several cytomembrane lipids, in particular phosphatidic acid, which proved to be essential to CytK-elicited cell death. Together, these results add new insights into the cytotoxic mechanism of CytK.

Preventing Bacterial Translocation in Patients with Leaky Gut Syndrome: Nutrition and Pharmacological Treatment Options.

Leaky gut syndrome is a medical condition characterized by intestinal hyperpermeability. Since the intestinal barrier is one of the essential components maintaining homeostasis along the gastrointestinal tract, loss of its integrity due to changes in bacterial composition, decreased expression levels of tight junction proteins, and increased concentration of pro-inflammatory cytokines may lead to intestinal hyperpermeability followed by the development of gastrointestinal and non-gastrointestinal diseases. Translocation of microorganisms and their toxic metabolites beyond the gastrointestinal tract is one of the fallouts of the leaky gut syndrome. The presence of intestinal bacteria in sterile tissues and distant organs may cause damage due to chronic inflammation and progression of disorders, including inflammatory bowel diseases, liver cirrhosis, and acute pancreatitis. Currently, there are no medical guidelines for the treatment or prevention of bacterial translocation in patients with the leaky gut syndrome; however, several studies suggest that dietary intervention can improve barrier function and restrict bacteria invasion. This review contains current literature data concerning the influence of diet, dietary supplements, probiotics, and drugs on intestinal permeability and bacterial translocation.

Fecal Microbiota Transplantation beyond Clostridioides Difficile Infection.

With advancing analytical methods for gut microbes, many studies have been conducted, revealing that gut microbes cause various diseases, including gastrointestinal and non-gastrointestinal diseases. Accordingly, studies have been actively conducted to analyze the effects on the prevention and treatment of these diseases through changes in intestinal microbes and control of dysbiosis. Fecal microbiota transplantation (FMT) is an effort and is currently being applied to Clostridioides difficile treatment in Korea. Many studies have demonstrated the application of FMT in inflammatory bowel disease, irritable bowel syndrome, non-alcoholic fatty liver disease, metabolic syndrome, obesity, and diabetes. With further studies and accumulation of evidence, FMT could help treat presently untreatable diseases in clinical practice.

An Investigation on the Occurrence and Molecular Characterization of Bacillus cereus in Meat and Meat Products in China

Bacillus cereus is a common foodborne pathogen that can cause both gastrointestinal and nongastrointestinal diseases. In this study, we collected 603 meat and meat products from 39 major cities in China. The positive contamination rate of B. cereus in the collected samples was 26.37% (159/603), and the contamination level in 5.03% (8/159) positive samples exceeded 1100 most probable number/g. The detection rates of virulence genes were 89.7% for the nheABC gene group, 37.1% for the hblACD gene cluster, 82.3% for cytK-2, and 2.9% for cesB. Notably, all isolates presented with multiple antibiotic resistance, and 99.43% of isolates were resistant to five classes of antibiotics. In addition, the multilocus sequence typing results indicated that all isolates were rich in genetic diversity. Collectively, we conducted a systematic investigation on the prevalence and characterization of B. cereus in meat and meat products in China, providing crucial information for assessing the risk of B. cereus occurrence in meat and meat products.

Activation of central adenosine A2B receptors mediate brain ghrelin-induced improvement of intestinal barrier function through the vagus nerve in rats

Leaky gut that is a condition reflecting intestinal barrier dysfunction has been attracting attention for its relations with many diseases such as irritable bowel syndrome or Alzheimer dementia. We have recently demonstrated that ghrelin acts in the brain to improve leaky gut via the vagus nerve. In the present study, we tried to clarify the precise central mechanisms by which ghrelin improves intestinal barrier function through the vagus nerve. Colonic permeability was estimated in vivo by quantifying the absorbed Evans blue in colonic tissue in rats. Adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), blocked the intracisternal ghrelin-induced improvement of intestinal hyperpermeability while dopamine, cannabinoid or opioid receptor antagonist failed to prevent it. Since DPCPX can block adenosine A1 and adenosine A2B receptors, we examined which subtype is involved in the mechanism. Intracisternal injection of adenosine A2B agonist but not adenosine A1 agonist improved colonic hyperpermeability, while peripheral injection of adenosine A2B agonist failed to improve it. Intracisternal adenosine A2B agonist-induced improvement of colonic hyperpermeability was blocked by vagotomy. Adenosine A2B specific antagonist, alloxazine blocked the ghrelin- or central vagal stimulation by 2-deoxy-d-glucose-induced improvement of intestinal hyperpermeability. These results suggest that activation of adenosine A2B receptors in the central nervous system is capable of improving intestinal barrier function through the vagal pathway, and the adenosine A2B receptors may mediate the ghrelin-induced improvement of leaky gut in a vagal dependent fashion. These findings may help us understand the pathophysiology in not only gastrointestinal diseases but also non-gastrointestinal diseases associated with the altered intestinal permeability.

Probiotics-derived metabolite ameliorates skin allergy by promoting differentiation of FOXP3+ regulatory T cells

Probiotics have shown their potent immunomodulatory effects and are considered a promising alternative for the prevention and treatment of inflammatory disorders.1 However, lack of precise action mechanisms of probiotics restrained their application, especially for the treatment of non-gastrointestinal diseases such as skin allergies including atopic dermatitis and allergic contact dermatitis.2 Previously, we have shown that the combination of rationally selected 5 probiotic bacteria strains (known as IRT5) has persuasive therapeutic effects on autoimmunity.

Prevalence, Virulence Feature, Antibiotic Resistance and MLST Typing of Bacillus cereus Isolated From Retail Aquatic Products in China.

Bacillus cereus is one of the most important foodborne pathogenic microorganisms, which can lead to gastrointestinal and non-gastrointestinal diseases. However, the potential risk of B. cereus in aquatic products in China has not been comprehensively evaluated yet. In this study, a total of 860 aquatic samples from three types of retail aquatic products were collected from 39 major cities in China from 2011 to 2016. The contamination, distribution of virulence genes, antibiotic resistance and genetic diversity of B. cereus isolates were measured and analyzed. Of all the samples, 219 (25.47%) were positive for B. cereus and 1.83% (4/219) of the samples had contamination levels of more than 1,100 most probable number (MPN)/g. Different isolates had virulence potential, within which 59.6% (164/275) contained all three kinds of enterotoxin genes (nhe, hbl, and cytK-2) and 5.1% (14/275) possessed cereulide encoding gene cesB. The antimicrobial resistance profiles revealed the universal antibiotic resistance to rifampin and most β-lactams, suggesting the necessity to continuously monitor the antibiotic resistance of B. cereus in aquatic products and to control drug use in aquaculture. In sum, our study indicates the potential hazards of B. cereus isolated from aquatic products to customers and may provide a reference for clinical treatment caused by B. cereus.

Characteristics of a transferable <italic>tet</italic>(45) gene conferring resistance to tetracyclines in probiotic<italic> Bacillus cereus</italic>

Probiotic microbes conferring health benefits to the hosts have attracted great concerns recently. Particularly, spore-forming Bacillus cereus ( B. cereus ), Gram-positive, aerobic or facultative anaerobic bacteria, have been widely used in probiotic preparations for different purposes, due to their high stability to harsh conditions. Probiotics are generally recognized as safe (GRAS) and showing satisfactory overall safety records till now. However, the safety of each probiotic isolate is not guaranteed. The verification of the absence of mobile antimicrobial resistance genes and virulence factors is a prerequisite for the approval of probiotic candidates, according to the guidelines suggested by the Food and Agriculture Organization (FAO) and World Health Organization (WHO). The role of B. cereus and other members of the B. cereus group in gastrointestinal and non-gastrointestinal diseases has not always gained sufficient attention in the past, particularly in view of their use as probiotics. Therefore, the presence of transferrable antimicrobial resistance genes will endow probiotics as a reservoir with increased ability of emergence and dissemination, during their wide and inadvertent use. Our previous study found that the presence of transferable tetracycline resistance gene tet (45) in a probiotic isolate B. cereus 9i (BC 9i) derived of animal feed additive. The aim of the present work was to systematically characterize this tet (45). The draft assembled genome of BC 9i was first used to analyze the genetic environment of tet (45). Meanwhile, multiple alignment and a maximum likelihood tree were built to conduct the phylogenetic relationship between tet (45) and othertetracycline efflux resistance genes. In addition, the 3D protein structures were predicted to identify differences between Tet(45) and the original Tet(45). Lastly, the tet (45) gene in BC 9i was cloned and transferred into Staphylococcus aureus RN4220 to the minimum inhibitory concentrations, in the presence and absence of classic inhibitors of efflux pumps. The phylogenetic analysis showed that the gene tet (45) in BC 9i was classified as a gene variant of tet (45), belonging to the major facilitator superfamily of membrane transporters. Additionally, the predicted structure of Tet(45) variant was similar to the original Tet(45), both sharing a 14-transmembrane helix core, although they exhibited subtle structural differences in the loop regions and α-helixes. Lastly, the resistance to tetracyclines in tet (45) variant was suppressed in the presence of efflux pump inhibitors. These results indicated that the tet (45) variant in BC 9i encoded a efflux pump against tetracyclines. Collectively, our findings suggest that such probiotic isolates harboring transferable antimicrobial resistance genes may consist a potential risk for public health. It sheds light on the subsequent screening of probiotic candidates and the appropriate application of probiotics for various purposes, to promote and improve One Health.

Ghrelin acts in the brain to block colonic hyperpermeability in response to lipopolysaccharide through the vagus nerve

Brain ghrelin plays a role in gastrointestinal functions. Among them, ghrelin acts centrally to stimulate gastrointestinal motility and induce visceral antinociception. Intestinal barrier function, one of important gastrointestinal functions, is also controlled by the central nervous system. Little is, however, known about a role of central ghrelin in regulation of intestinal permeability. The present study was performed to clarify whether brain ghrelin is also involved in regulation of intestinal barrier function and its mechanism. Colonic permeability was estimated in vivo by quantifying the absorbed Evans blue in colonic tissue in rats. Intracisternal injection of ghrelin dose-dependently abolished increased colonic permeability in response to LPS while intraperitoneal injection of ghrelin at the same dose or intracisternal injection of des-acyl-ghrelin failed to block it. Carbachol potently attenuated LPS-induced intestinal hyperpermeability, and atropine or bilateral subdiaphragmatic vagotomy prevented the improvement of intestinal hyperpermeability by central ghrelin. Intracisternal (D-Lys3)-GHRP-6, a selective ghrelin receptor antagonist, significantly blocked improvement of intestinal barrier function by intravenously administered 2-deoxy-d-glucose, central vagal stimulant. Intracisternal injection of orexin 1 receptor antagonist, SB-334867 blocked intracisternal ghrelin-induced improvement of colonic hyperpermeability. These results suggest that exogenously administered or endogenously released ghrelin acts centrally to improve a disturbed intestinal barrier function through orexinergic signaling and the vagal cholinergic pathway. Central ghrelin may be involved in the pathophysiology and be a novel therapeutic option in not only gastrointestinal diseases such as irritable bowel syndrome but also non-gastrointestinal diseases associated with the altered intestinal permeability.

Low FODMAP Diet: Evidence, Doubts, and Hopes.

Food is often considered to be a precipitating factor of irritable bowel syndrome (IBS) symptoms. In recent years, there has been a growing interest in FODMAPs (Fermentable Oligo-, Di-, Mono-saccharides, And Polyols), which can be found in many common foods. A low FODMAP diet (LFD) is increasingly suggested for IBS treatment. However, long-term, large, randomized controlled studies are still lacking, and certainties and doubts regarding LFDs have grown, often in a disorderly and confused manner. Some potential LFD limitations and concerns have been raised, including nutritional adequacy, cost, and difficulty in teaching the diet and maintaining it. Most of these limitations can be solved with the involvement of a skilled nutritionist, who can clearly explain the different phases of the LFD and ensure nutritional adequacy and compliance. Further studies should focus on new methods of teaching and learning the LFD and on predictors of response. Moreover, particular interest should be focused on the possible use of LFD in gastrointestinal diseases other than functional disorders and, possibly, also in non-gastrointestinal diseases. The aim of the present review was to clarify the effective and appropriate indications and limitations of an LFD and to discuss its possible future uses.

Polymeric carriers for enhanced delivery of probiotics.

Probiotics are live microorganisms (usually bacteria), which are defined by their ability to confer health benefits to the host, if administered adequately. Probiotics are not only used as health supplements but have also been applied in various attempts to prevent and treat gastrointestinal (GI) and non-gastrointestinal diseases such as diarrhea, colon cancer, obesity, diabetes, and inflammation. One of the challenges in the use of probiotics is putative loss of viability by the time of administration. It can be due to procedures that the probiotic products go through during fabrication, storage, or administration. Biocompatible and biodegradable polymers with specific moieties or pH/enzyme sensitivity have shown great potential as carriers of the bacteria for 1) better viability, 2) longer storage times, 3) preservation from the aggressive environment in the stomach and 4) topographically targeted delivery of probiotics. In this review, we focus on polymeric carriers and the procedures applied for encapsulation of the probiotics into them. At the end, some novel methods for specific probiotic delivery, possibilities to improve the targeted delivery of probiotics and some challenges are discussed.

Late complications associated with totally implantable venous access port implantation via the internal jugular vein.

Several studies have analyzed late complications associated with totally implantable venous access ports (TIVAP) implantation via the internal jugular vein (IJV); however, the reported results are inconclusive. The aim of the study is to elucidate the characteristics and risk factors of late complications associated with TIVAP implantation via the IJV. The study included 482 patients who underwent TIVAP implantation for long-term chemotherapy and/or nutritional support between April 2012 and December 2017. Most patients (95.2%) had malignant diseases. Events requiring TIVAP removal were defined as TIVAP-related complications. The median TIVAP and global follow-ups were 319 days (IQR 152-661) and 218,971 catheter days, respectively. The 3-year cumulative TIVAP availability rate was 70%. There were 44 complications (incidence of 9.1%; 0.201 complications/1000 catheter days). Infectious, catheter-related, and port-related complications occurred in 21, 14, and 9 patients, respectively with infectious complications occurring earlier and more frequently than catheter- and port-related complications. Multivariate analysis revealed that age < 65 years and presence of non-gastrointestinal diseases were significant unfavorable factors for TIVAP-related complications. Patients with 1 and 2 of these factors had an elevated risk (2.2 and 5.4 times, respectively) compared with those without. Among the late complications associated with TIVAP implantation via the IJV, infectious complications occur earlier and more frequently than catheter- and port-related complications. Patients with an age < 65 years and having non-gastrointestinal diseases have a significantly high risk of TIVAP-related complications.

Gut microbiata: underestimated or exaggerated?

Human gastrointestinal tract contains a large diversity of commensal microorganisms, which is many times more than the human living cells. In the last decade, we had enormous number of research on the association with diseases and gut microbiota composition. There is a clear increase in the number of pathological conditions associated with dysbiosis in time. Also, the range of diseases are increased and distributed to many disciplines, non-gastrointestinal diseases are also increasingly reported. Gut microbiota has multiple functions and new applications for diagnosis and therapeutics of diseases. Probiotics are widely used in health and disease states. Probably further high quality scientific research will determine the exact place of microbiota and probiotics in human health in the future.