Gastrointestinal neuromuscular apparatus: An underestimated target of gut microbiota

Over the last few years, the importance of the resident intestinal microbiota in the pathogenesis of several gastrointestinal diseases has been largely investigated. Growing evidence suggest that microbiota can influence gastrointestinal motility. The current working hypothesis is that dysbiosis-driven mucosal alterations induce the production of several inflammatory/immune mediators which affect gut neuro-muscular functions. Besides these indirect mucosal-mediated effects, the present review highlights that recent evidence suggests that microbiota can directly affect enteric nerves and smooth muscle cells functions through its metabolic products or bacterial molecular components translocated from the intestinal lumen. Tolllike receptors, the bacterial recognition receptors, are expressed both on enteric nerves and smooth muscle and are emerging as potential mediators between microbiota and the enteric neuromuscular apparatus. Furthermore, the ongoing studies on probiotics support the hypothesis that the neuromuscular apparatus may represent a target of intervention, thus opening new physiopathological and therapeutic scenarios.

Anti-tumor necrosis factor α therapy associates to type 17 helper T lymphocytes immunological shift and significant microbial changes in dextran sodium sulphate colitis

BACKGROUND Anti-tumor necrosis factor α(TNFα) represents the best therapeutic option to induce mucosal healing and clinical remission in patients with moderate-severe ulcerative colitis. On the other side gut microbiota plays a crucial role in pathogenesis of ulcerative colitis but few information exists on how microbiota changes following anti-TNFα therapy and on microbiota role in mucosal healing.AIM To elucidate whether gut microbiota and immune system changes appear following anti TNFα therapy during dextran sulfate sodium(DSS) colitis.METHODS Eighty C57 BL/6 mice were divided into four groups: "No DSS", "No DSS + antiTNFα", "DSS" and "DSS + anti-TNFα". "DSS" and "DSS + anti-TNFα" were treated for 5 d with 3% DSS. At day 3, mice whithin "No DSS+anti-TNFα" and"DSS+anti-TNFα" group received 5 mg/kg of an anti-TNFα agent. Forty mice were sacrificed at day 5, forty at day 12, after one week of recovery post DSS. The severity of colitis was assessed by a clinical score(Disease Activity Index), colon length and histology. Bacteria such as Bacteroides, Clostridiaceae, Enterococcaceae and Fecalibacterium prausnitzii(F. prausnitzii) were evaluated by quantitative PCR.Type 1 helper T lymphocytes(Th1), type 17 helper T lymphocytes(Th17) and CD4+ regulatory T lymphocytes(Treg) distributions in the mesenteric lymph node(MLN) were studied by flow cytometry.RESULTS Bacteria associated with a healthy state(i.e., such as Bacteroides, Clostridiaceae and F. prausnitzii) decreased during colitis and increased in course of anti-TNFαtreatment. Conversely, microorganisms belonging to Enterococcaceae genera,which are linked to inflammatory processes, showed an opposite trend.Furthermore, in colitic mice treated with anti-TNFα microbial changes were associated with an initial increase(day 5 of the colitis) in Treg cells and a consequent decrease(day 12 post DSS) in Th1 and Th17 frequency cells. Healthy mice treated with anti-TNFα showed the same histological, microbial and immune features of untreated colitic mice. "No DSS + anti-TNFα" group showed a lymphomononuclear infiltrate both at 5 th and 12 th d at hematoxylin and eosin staining, an increase of in Th1 and Th17 frequency at day 12, an increase of Enterococcaceae at day 5, a decrease of Bacteroides and Clostridiaceae at day 12.CONCLUSION Anti-TNFα treatment in experimental model of colitis improves disease activity but it is associated to an increase in Th17 pathway together with gut microbiota alteration.

Diagnostic Accuracy of MRI in Primary Cervical Cancer

Introduction: Magnetic resonance imaging (MRI) studies obtained during the initial staging of patients affected by uterine cervical cancer were compared to the final histological report after surgery. Methods: Data were retrieved from published papers. Results: MRI detection of lymph node metastases shows a sensitivity of 49.3% (1209 patients) and a specificity of 87.7% (1182 patients). Parametrial involvement detection has 66.2% sensitivity (1288 patients) and 83.6% specificity (1282 patients). MRI tumor size evaluation shows significant error. Even detection of over 1 cm diameter primary tumor can fail. MRI appears promising in the detection of myometrial and endometrial involvement. Conclusions: Primary uterine cervical cancer evaluation with routine MRI has a limited accuracy especially in the detection of lymph node involvement and parametrial invasion. It is not sensitive enough to replace histology of dissected nodes and parametria. Tumor size estimation is imprecise. Detection of myometrial and endometrial invasion using MRI might be possible. Awareness of MRI limitations is crucial in primary cervical cancer staging.

Gut microbiome beats two to zero host genome

The gut microbiota and its genomic scaffold, exceeding the human one nearly 500 times, substantially affect human health and diseases. Host-microbe interactions, exerted through microbial biochemical and immunological activities, contain pathogen burden, control neurological and endocrine signalling, enterocyte wellness, energy biosynthesis, gut dysbiosis, complement gaps of host metabolic pathways, finally contributing to human physiology and disease within the gastrointestinal district and through gut-liver and gut-brain axis (1). Regardless substantial advances in correlating microbiota modulation and perturbation with various influencers, the specific impact of internal and external stimuli need to be definitely assigned though causality relationships beyond correlative measures. Host origin or genetic background, age, sanitation, delivery mode, breast-feeding and weaning, infections, diet, drugs, but also exercise, sleep, stress have been reviewed in a wide range of recent literature (2). All external (i.e., food, pathogens) and internal (i.e., microbiota) host modulating factors, both, can be conceptually synthetized by the term "exposome" which we are exposed to in the lifetime and which drives both individual enterophenotypes and disease phenotypes (3). Integrative descriptive and functional charts of microbiota allow the description of the microbiota-host Holobionts system, relationship that can be employed in understanding personalized physiology and nutrition, thus providing patient-tailored therapies (Figure 1). To investigate microbiota unbalance and passage from healthy to disease or unhealthy status, individual baseline compositions and variations within an individual's own range are required.