• Prebiotics
• Humans
• Gastrointestinal Microbiome/drug effects
• Feces/microbiology
• Fermentation
• Polysaccharides/metabolism
• Colon/microbiology
• Colon/metabolism
• Fatty Acids, Volatile/metabolism
• Transcriptome
• Gene Expression Profiling
• Dietary Fiber/metabolism
• Lactobacillus/metabolism
• Lactobacillus/genetics
• Bacteria/genetics
• Bacteria/metabolism

• KB-17-003.02-023 IP/OP program Systems Biology

• Microbiota
• Bacteria/metabolism
• Bacteria/classification
• Bacteria/genetics
• Models, Biological

• R01GM121950 U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
• UH2AG064704 U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
• DE-AC02-05CH11231 U.S. Department of Energy (DOE)
• DE-SC0020403 U.S. Department of Energy (DOE)
• DE-SC0012704 U.S. Department of Energy (DOE)
• 1457695 National Science Foundation (NSF)
• T32GM100842 U.S. Department of Health & Human Services | National Institutes of Health (NIH)

• endometriosis
• estrogen
• gut microbiota
• inflammation
• probiotics

Clostridioides difficile infection (CDI) is a health issue of utmost significance in Europe and North America, due to its high prevalence, morbidity, and mortality rate. The clinical spectrum of CDI is broad, ranging from asymptomatic to deadly fulminant colitis. When associated with chronic kidney disease (CKD), CDI is more prevalent and more severe than in the general population, due to specific risk factors such as impaired immune system, intestinal dysmotility, high antibiotic use leading to disturbed microbiota, frequent hospitalization, and PPI use. We performed a systematic review on the issue of prevention and treatment of CDI in the CKD population, analysing the suitable randomized controlled cohort studies published between 2000 and 2021. The results show that the most important aspect of prevention is isolation and disinfection with chlorine-based solution and hydrogen peroxide vapour to stop the spread of bacteria. In terms of prevention, using Lactobacillus plantarum (LP299v) proved to be more efficient than disinfection measures in transplant patients, leading to higher cure rates and less recurrent episodes of CDI. Treatment with oral fidaxomycin is more effective than with oral vancomycin for the initial episode of CDI in CKD patients. Faecal microbiota transplantation (FMT) is more effective than vancomycin in recurrent CDI in CKD patients. More large-sample RCTs are necessary to conclude on the best treatment and prevention strategy of CDI in CKD patients.

• NOD mice
• animal models
• autoimmune
• cecal material transfer
• gene expression
• histone modification
• innate immune
• microRNA
• microbiome
• type 1 diabetes

• Animals
• Anti-Bacterial Agents/pharmacology
• Autoimmune Diseases
• Bacteria/classification
• Bacteria/drug effects
• Cecum/immunology
• Cecum/microbiology
• Diabetes Mellitus, Type 1/immunology
• Disease Models, Animal
• Female
• Gastrointestinal Microbiome/drug effects
• Gastrointestinal Microbiome/physiology
• Gene Expression
• Histone Code
• Intestines/immunology
• Male
• Metabolic Networks and Pathways
• Metagenome
• Mice
• Mice, Inbred NOD
• MicroRNAs

• R01 DK120679 NIDDK NIH HHS
• R01 DK110014 NIDDK NIH HHS
• P01 HL147823 NHLBI NIH HHS
• R35 GM139655 NIGMS NIH HHS
• R01 GM128955 NIGMS NIH HHS

The field of the gut microbiota is still a relatively young science area, yet many studies have already highlighted the translational potential of microbiome research in the context of human health and disease. However, like in many new fields, discoveries are occurring at a fast pace and have provided new hope for the development of novel clinical applications in many different medical conditions, not in the least in metabolic disorders. This rapid progress has left the field vulnerable to premature claims, misconceptions and criticism, both from within and outside the sector. Tackling these issues requires a broad collaborative effort within the research field and is only possible by acknowledging the difficulties and challenges that are faced and that are currently hindering clinical implementation. These issues include: the primarily descriptive nature of evidence, methodological concerns, disagreements in analysis techniques, lack of causality, and a rather limited molecular-based understanding of underlying mechanisms. In this review, we discuss various studies and models that helped identifying the microbiota as an attractive tool or target for developing various translational applications. We also discuss some of the limitations and try to clarify some common misconceptions that are still prevalent in the field.

• causality
• confounding factors
• correlation
• diabetes
• gut microbiota
• metabolism
• mice
• obesity

• aetiology
• autism spectrum disorder
• clinician
• comorbidities
• diet
• faecal microbial transplant
• microbiome
• prebiotics
• probiotics

• Autism Spectrum Disorder/microbiology
• Autism Spectrum Disorder/therapy
• Diet/methods
• Fecal Microbiota Transplantation
• Female
• Gastrointestinal Microbiome/physiology
• Humans
• Male
• Microbiota/physiology
• Mouth/microbiology
• Prebiotics
• Probiotics/therapeutic use
• Vagina/microbiology

• Project No. PVC-ECR-2016, Biotek Abadi - Vote No. GBA-808138 and GBA-808813 PVC Award Grant & External Industry Grant

Probiotics are commensal or nonpathogenic microbes that confer beneficial effects on the host through several mechanisms such as competitive exclusion, antibacterial effects, and modulation of immune responses. Some probiotics have been found to regulate immune responses via immune regulatory mechanisms. T regulatory (Treg) cells, T helper cell balances, dendritic cells, macrophages, B cells, and natural killer (NK) cells can be considered as the most determinant dysregulated mediators in immunomodulatory status. Recently, fecal microbiota transplantation (FMT) has been defined as the transfer of distal gut microbial communities from a healthy individual to a patient's intestinal tract to cure some immune disorders (mainly inflammatory bowel diseases). The aim of this review was followed through the recent literature survey on immunomodulatory effects and mechanisms of probiotics and FMT and also efficacy and safety of probiotics and FMT in clinical trials and applications.

• Alcohols/metabolism
• Biofuels/microbiology
• Coculture Techniques/methods
• Environmental Restoration and Remediation/methods
• Garbage
• Gastrointestinal Microbiome
• Humans
• Urea/metabolism

• Antibiotic associated diarrhea
• Clostridium difficile
• Polymerase chain reaction
• Toxigenic culture

Clostridium difficile (CD) is a serious and increasingly prevalent healthcare-associated infection. The pathogenesis of CD infection (CDI) involves the acquisition of CD with a concurrent disruption of the native gut flora. Antibiotics are a major risk although other contributing factors have also been identified. Clinical management combines discontinuation of the offending antibiotic, initiation of CD-specific antibiotic therapy, probiotic agent use, fecal microbiota transplantation (FMT), and surgery as the “last resort” option. The aim of this study is to review short-term clinical results following the implementation of FMT protocol (FMTP) at our community-based university hospital.

After obtaining Institutional Review Board and Infection Control Committee approvals, we implemented an institution-wide FMTP for patients diagnosed with CDI. Prospective tracking of all patients receiving FMT between July 1, 2015, and February 1, 2017, was conducted using REDCap™ electronic data capture system. According to the FMTP, indications for FMT included (a) three or more CDI recurrences, (b) two or more hospital admissions with severe CDI, or (c) first episode of complicated CDI (CCDI). Risk factors for initial infection and for treatment failure were assessed. Patients were followed for at least 3 months to monitor for cure/failure, relapse, and side effects. Frozen 250 mL FMT samples were acquired from OpenBiome (Somerville, MA, USA). After 4 h of thawing, the liquid suspension was applied using colonoscopy, beginning with terminal ileum and proceeding distally toward mid-transverse colon. Monitored clinical parameters included disease severity (Hines VA CDI Severity Score or HVCSS), concomitant medications, number of FMT treatments, non-FMT therapies, cure rates, and mortality. Descriptive statistics were utilized to outline the study results.

A total of 35 patients (mean age 58.5 years, 69% female) were analyzed, with FMT-attributable primary cure achieved in 30/35 (86%) cases. Within this subgroup, 2/30 (6.7%) patients recurred and were subsequently cured with long-term oral vancomycin. Among five primary FMT failures (14% total sample), 3 (60%) achieved medical cure with long-term oral vancomycin therapy and 2 (40%) required colectomy. For the seven patients who either failed FMT or recurred, long-term vancomycin therapy was curative in all but two cases. For patients with severe CDI (HVCSS ≥3), primary and overall cure rates were 6/10 (60%) and 8/10 (80%), respectively. Patients with CCDI (n = 4) had higher HVCSS (4 vs. 3) and a mortality of 25%. Characteristics of patients who failed initial FMT included older age (70 vs. 57 years), female sex (80% vs. 67%), severe CDI (80% vs. 13%), and active opioid use during the initial infection (60% vs. 37%) and at the time of FMT (60% vs. 27%). The most commonly reported side effect of FMT was loose stools.

This pilot study supports the efficacy and safety of FMT administration for CDI in the setting of a community-based university hospital. Following FMTP implementation, primary (86%) and overall (94%) nonsurgical cure rates were similar to those reported in other studies. The potential role of opioids as a modulator of CDI warrants further clinical investigation.

• Clinical protocol implementation
• Clostridium difficile
• Clostridium difficile infection
• fecal microbiota transplantation
• infectious colitis

Fecal microbiota transplantation (FMT) is effective in recurrent Clostridium difficile infection (rCDI). Knowledge of the safety and efficacy of FMT treatment in immune deficient patients is scarce. FMT has been suggested as a potential method for an increasing number of new indications besides rCDI. Among our FMT-treated rCDI patients, we reviewed those with major comorbidities: two human immunodeficiency virus patients, six haemodialysis patients, two kidney transplant patients, two liver transplant patients and a patient with chronic lymphatic leukaemia. We also reviewed those treated with FMT for indications other than rCDI: Salmonella carriage (two patients), trimethylaminuria (two patients), small intestinal bacterial overgrowth (SIBO; one patient), and lymphocytic colitis (one patient), as well as a common variable immunodeficiency patient with chronic norovirus infection and ESBL-producing Escherichia coli (E. coli) carriage. Of the thirteen rCDI patients treated with FMT, eleven cleared the CDI. The observed adverse events were not directly attributable to FMT. Concerning the special indications, both Salmonellas and ESBL-producing E. coli were eradicated. One trimethylaminuria patient and one SIBO-patient reported a reduction of symptoms. Three patients did not experience a benefit from FMT: chronic norovirus, lymphocytic colitis and the other fish malodour syndrome. There were no reported side effects in this group. FMT appeared to be safe and effective for immunocompromised patients with rCDI. FMT showed promise for the eradication of antibiotic-resistant bacteria, but further research is warranted.

• Faecal microbiota transplantation
• Antibiotic resistance
• Clostridium difficile infection
• Microbiota
• Immunodeficiency
• Salmonella infection

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents/therapeutic use
• Clostridioides difficile/pathogenicity
• Coinfection
• Comorbidity
• Drug Resistance, Bacterial
• Enterocolitis, Pseudomembranous/diagnosis
• Enterocolitis, Pseudomembranous/immunology
• Enterocolitis, Pseudomembranous/microbiology
• Enterocolitis, Pseudomembranous/therapy
• Fecal Microbiota Transplantation/adverse effects
• Feces/microbiology
• Female
• Humans
• Immunocompromised Host
• Male
• Middle Aged
• Recurrence
• Risk Factors
• Treatment Outcome
• Young Adult

Clostridium difficile (C. difficile) is a common cause of antibiotic-­associated diarrhea (AAD), being responsible for 15­-25% of all AAD cases. The purpose of this literature review is to determine the cost-effectiveness of fecal microbiota transplantation (FMT) and how it compares in this regard to the standard treatments of choice for recurrent C. difficile infection (CDI). The review of the literature along with the evaluation of three comparative cost effective analyses yielded findings consistent with the view that FMT is the most cost-effective option in treating recurrent CDI. There are some (but considerably less) data indicating that FMT may be a cost effective strategy in treating initial CDI, as well. The superior cost-effectiveness of FMT as compared to the preferred standards of treatment for recurrent CDI suggest FMT use should become more integrated in routine clinical practice. Increased utilization of FMTs would allow for better control of this increasingly problematic disease as well as lower costs associated with its management.

• antibiotics
• c. difficle
• cost effectiveness
• diarrhea
• fecal microbiota transplantation

• Animals
• Diabetes Mellitus
• Diet, High-Fat/adverse effects
• Endotoxemia
• Energy Metabolism/physiology
• Gastrointestinal Microbiome/genetics
• Gastrointestinal Microbiome/physiology
• Germ-Free Life
• Humans
• Inflammation/metabolism
• Insulin Resistance
• Lipopolysaccharides/metabolism
• Mice
• Models, Biological
• Nutrition Disorders/therapy
• Obesity/microbiology
• Probiotics/therapeutic use

• Autism
• Functional bowel disease
• Gastrointestinal
• Inflammation
• Microbiome
• Probiotics

• Abdominal Pain/drug therapy
• Abdominal Pain/immunology
• Abdominal Pain/microbiology
• Autism Spectrum Disorder/immunology
• Autism Spectrum Disorder/microbiology
• Child
• Constipation/drug therapy
• Constipation/immunology
• Constipation/microbiology
• Diarrhea/drug therapy
• Diarrhea/immunology
• Diarrhea/microbiology
• Gastrointestinal Diseases/drug therapy
• Gastrointestinal Diseases/immunology
• Gastrointestinal Diseases/microbiology
• Gastrointestinal Microbiome/immunology
• Humans
• Inflammation
• Probiotics/therapeutic use

• autoimmune disease
• celiac disease
• food allergy
• inflammatory bowel disease
• metabolomics
• multi-omic data integration
• necrotizing enterocolitis
• obesity
• probiotics

• ulcerative colitis
• crohn’s disease
• inflammatory bowel disease
• clostridium difficile
• microbiota

• R01 DK092374 NIDDK NIH HHS
• R01 DK100345 NIDDK NIH HHS

Clostridium difficile (C. difficile) infection (CDI) is the most common cause of ­healthcare-associated infections in US hospitals. The epidemic strain NAP1/BI/ribotype 027 accounts for outbreaks worldwide, with increasing mortality and severity. CDI is acquired from an endogenous source or from spores in the environment, most easily acquired during the hospital stay. The use of antimicrobials disrupts the intestinal microflora enabling C. difficile to proliferate in the colon and produce toxins. Clinical diagnosis in symptomatic patients requires toxin detection from stool specimens and rarely in combination with stool culture to increase sensitivity. However, stool culture is essential for epidemiological studies. Oral metronidazole is the recommended therapy for milder cases of CDI and oral vancomycin or fidaxomicin for more severe cases. Treatment of first recurrence involves the use of the same therapy used in the initial CDI. In the event of a second recurrence oral vancomycin often given in a tapered dose or intermittently, or fidaxomicin may be used. Fecal transplantation is playing an immense role in therapy of recurrent CDI with remarkable results. Fulminant colitis and toxic megacolon warrant surgical intervention. Novel approaches including new antibiotics and immunotherapy against CDI or its toxins appear to be of potential value.

• Clostridium difficile infection
• fecal microbial transplantation
• fidaxomicin
• humanized monoclonal antitoxin antibodies
• toxic megacolon