Dysbiosis of gut microbiota in inflammatory bowel disease: Current therapies and potential for microbiota-modulating therapeutic approaches

There is a growing body of evidence reinforcing the unique connections between the host microbiome, health, and diseases. Due to the extreme importance of the symbiotic relationship between the intestinal microbiome and the host, it is not surprising that any alteration in the gut microbiota would result in various diseases, including inflammatory bowel disease (IBD), Crohn’s disease, (CD) and ulcerative colitis (UC). IBD is a chronic, relapsing-remitting condition that is associated with significant morbidity, mortality, compromised quality of life, and costly medical care. Dysbiosis is believed to exacerbate the progression of IBD. One of the currently used treatments for IBD are anti-tumor necrosis factor (TNF) drugs, representing a biologic therapy that is reported to have an impact on the gut microbiota composition. The efficacy of anti-TNF agents is hindered by the possibility of non-response, which occurs in 10-20% of treated patients, and secondary loss of response, which occurs in up to 30% of treated patients. This underscores the need for novel therapies and studies that evaluate the role of the gut microbiota in these conditions. The success of any therapeutic strategy for IBD depends on our understanding of the interactions that occur between the gut microbiota and the host. In this review, the health and disease IBD-associated microbiota patterns will be discussed, in addition to the effect of currently used therapies for IBD on the gut microbiota composition, as well as new therapeutic approaches that can be used to overcome the current treatment constraints

Protective effect of L-arginine in experimentally induced Necrotizing Enterocolitis in rats

Necrotizing enterocolitis (NEC) is a leading cause of mortality and morbidity in the neonatal intensive care unit which recently the etiology of NEC remains unclear, prevention and treatment strategies are often inadequate. Accordingly, a lot of research was conducted to evaluate L-arginine as one of the effective medications to protect the premature infants, where. The objective of the current study was to test the hypothesis that administration of L-arginine would have a protective effect in experimentally induced necrotizing enterocolitis in rats. The study was conducted on 46 male albino rats which were divided into three main groups:  Control group, L-arginine group, and the experimental group which has been divided into two sub-groups; Group A: received Lipopolysaccharides to induce NEC, Group B: injected by L-arginine prior to the disease induced by endotoxin, asphyxia and cold stress. After the animals had been scarified, histological changes were evaluated, gene expression of both iNOS and IL-12 were measured, and apoptosis also was detected by flowcytometry technique. The findings observed a significant increase in the expression of iNOS gene and IL-12 gene and a noticeable decrease of the apoptosis index. In addition, administration of L-arginine attenuated body weight, body temperature, and the histological changes were altered by LPS/asphyxia. As such, the study was able to demonstrate that L-arginine administration significant protective effect against NEC, but further clinical studies are still required on preterm infant to confirm these results. Key words: Necrotizing enterocolitis, L-arginine, Interleukin-12, Inducible nitric oxide synthase, Lipopolysaccharides, Messenger Ribonucleic acid (mRNA

Protective Impact of L-arginine against Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is the most common acute surgical disease in preterm infants in intensive neonatal care. Premature infants are infant born prematurely and have a low birth weight. The disease is characterized by an inflammatory process in the intestines, which sometimes worsen and reach the level of necrosis. This process, in the intestinal wall, can destroy and kill the tissue of the intestinal wall and, later, it makes an intestinal perforation. Intestinal contents, in this case, leak to the abdominal cavity, endangering the child's life. Different studies showed that the arginine level in many premature infants is low, and subsequent studies have linked low arginine plasma concentrations with NEC disease. This paper concerned with awareness of this disease, its symptoms and its causes, in addition to L-arginine medication role in necrotizing enterocolitis (NEC) treatment, which is a semi essential cationic amino acid

Attributes of intestinal microbiota composition and their correlation with clinical primary non-response to anti-TNF-α agents in inflammatory bowel disease patients

The largest microbial aggregation in the human body exists in the gastrointestinal tract. The microbiota in the host gastrointestinal tract comprises a diverse ecosystem, and the intestinal microbiota plays a vital role in maintaining gut homeostasis. This study aims to examine whether the gut microbiota influences unresponsiveness to anti-TNF-α treatments in primary nonresponder patients, and consequently identify the responsible microbes as biomarkers of unresponsiveness. Stool samples were collected from a cohort of patients with an established diagnosis of IBD, either ulcerative colitis (UC) or Crohn’s disease (CD), following completion of the induction phase of anti TNF therapy. 16S rRNA sequencing analysis was used to examine the pattern of microbiota communities in fecal samples. The quality and quantity of fecal microbiota were compared in responder and primary nonresponder IBD patients following anti-TNF-α therapy. As per our hypothesis, a difference in gut microbiome composition between the two patient subgroups was observed. A decreased abundance of short-chain fatty acid (SCFA)-producing bacteria, including Anaerostipes, Coprococcus, Lachnospira, Roseburia, and Ruminococcus, was detected in non-responsive patients, which was the hallmark of dysbiosis. Biomarkers of dysbiosis that were identified as predictors of clinical nonresponse, included Klebsiella, Eubacteriaceae, RF32, Bifidobacterium_animalis, and Muribaculaceae—previously known as S24-7. Signature biomarkers showed dramatic alteration in the composition of gut microbiota in patients who demonstrated primary nonresponse to anti-TNF-α agents. Dysbiosis, with features including a dropped biodiversity, augmentation in opportunistic pathogenic microbiota, and a lack of SCFA-producing bacteria, is a prominent feature of the microbiome of primary nonresponders to anti-TNF-α therapy

The Epidemiology and Outcome of Biliary Atresia: Saudi Arabian National Study (2000–2018)

BackgroundThe epidemiology and outcomes of biliary atresia (BA) have been well-documented in national cohorts from two main ethnicities, namely, the Asian Orientals and Caucasians, with incidence ranging from 1 in 5,000 to 1 in 9,000 live births in East Asia and 1 in 15,000 to 19,000 live births in Europe and North America.ObjectiveWe report the first nationwide BA study outside North America, Europe, and East Asia to describe the epidemiology and outcomes of BA in Saudi Arabia.MethodsA national database of BA cases diagnosed between 2000 and 2018 was analyzed. We assessed clearance of jaundice (bilirubin <20 μmol/L) in all cases that underwent Kasai portoenterostomy (KPE). We then estimated survival using the Kaplan–Meier method with endpoints of liver transplantation (LT), death, or survival with native liver (SNL).ResultsBA was diagnosed in 204 infants (106 females; 10% pre-term). The incidence of BA was 1 in 44,365, or 2.254 in 100,000 live births (range, 0.5–4 in 100,000). Polysplenia was diagnosed in 22 cases (11%). The median age at referral was 65 days. A total of 146 children (71.5%) underwent KPE at a median age of 70 days. Clearance of jaundice was achieved in 66 of the 146 (45%) infants. The 10-year SNL after KPE was 25.5%, and the overall 10-year estimated survival was 72.5%. The Kaplan–Meier survival curves for patients undergoing KPE at the age of <60, 61–90, and >90 days showed a SNL rate at 51.6, 33, and 12.5%, respectively, at 5 years (P < 0.001). The 2-, 5-, and 10-year post-LT survival rates were 92.5, 90.6, and 90%, respectively. Undergoing an initial KPE did not impact negatively on the overall LT survival rate when compared to BA cases that underwent primary LT (P = 0.88).ConclusionThe incidence rate of BA in Saudi Arabia is lower than the incidence reported elsewhere. Late referral of BA cases remains a problem in Saudi Arabia; as a result, the SNL rate was lower than reported by other national registries. Hence, national policies devoted to timely referral and earlier age at KPE are needed