Microbiota and Gut-Liver Axis: An Unbreakable Bond?

The gut microbiota, amounting to approximately 100 trillion (1014) microbes represents a genetic repertoire that is bigger than the human genome itself. Evidence on bidirectional interplay between human and microbial genes is mounting. Microbiota probably play vital roles in diverse aspects of normal human metabolism, such as digestion, immune modulation, and gut endocrine function, as well as in the genesis and progression of many human diseases. Indeed, the gut microbiota has been most closely linked to various chronic ailments affecting the liver, although concrete scientific data are sparse. In this narrative review, we initially discuss the basic epidemiology of gut microbiota and the factors influencing their initial formation in the gut. Subsequently, we delve into the gut-liver axis and the evidence regarding the link between gut microbiota and the genesis or progression of various liver diseases. Finally, we summarise the recent research on plausible ways to modulate the gut microbiota to alter the natural history of liver disease.

A Novel Method for the Prevention and Treatment of Small-for-Size Syndrome in Liver Transplantation.

BACKGROUND: Currently there is no consensus on the optimal management of small-for-size syndrome following liver transplantation. Here we describe a technique to alleviate portal hypertension and improve the hepatocyte reperfusion in small-for-size liver transplantation in a Lewis rat model. METHODS: The rats underwent trans-portal vein intra-hepatic portosystemic shunt using a self-developed porous conical tube (TPIPSS: Fig. 1) on small-for-size liver transplants (SFS) with right lobe graft. The treatment effect was evaluated by comparing hemodynamic parameters, morphological changes, serum parameters, ET-1 and eNOS expression, hepatocyte proliferation and apoptosis, CYP3A2 levels, postoperative complications, and survival between the two groups with SFS liver transplants. RESULTS: Porous conical prosthesis prolonged the filling time of small-for-size grafts. Moreover, grafts with TPIPSS showed a lower portal vein pressure, improved microcirculatory flow, alleviated histological changes, decreased ET-1 and increased eNOS expressions, and significantly less damage to liver function comparing to grafts without TPIPSS. Mean survival and overall 30-day survival were significantly higher in the TPIPSS group. CONCLUSIONS: These results demonstrate that porous conical tube as trans-portal vein intra-hepatic portosystemic shunt device is an effective way to alleviate portal vein hypertension and improve hepatocyte reperfusion after small-for-size liver transplantation.

Orthotopic kidney transplantation in mice: technique using cuff for renal vein anastomosis.

Mouse renal transplantation is a technically challenging procedure. Although the first kidney transplants in mice were performed over 34 years ago and refined some years later, the classical techniques of mouse renal transplantation required clamping both vena cava and aorta simultaneously and carry out suture anastomoses of the renal artery and vein in a heterotopic position. In our laboratory, we have successfully developed mouse orthotopic kidney transplantation for the first time, using a rapid "cuffed" renal vein technique for vessel anastomosis, wherein the donor's renal vein was inserted through an intravenous catheter, folded back and tied. During grafting, the cuffed renal vein was directly inserted into the recipient's renal vein without the need for the clamping vena cava and suturing of renal vein. This technique allowed for the exact transplantation of the kidney into the original position, compared to the classical technique, and has significantly shortened the clamping time due to a quicker and precise anastomosis of renal vein as described. This also allowed for a quicker recovery of the lower extremity activity, reduction in myoglobinuria with resultant kidney graft survival of 88.9%. Thus we believe that the cuffed renal vein technique simplifies microvascular anastomoses and affords important additional benefits.

Establishment of animal model of dual liver transplantation in rat.

The animal model of the whole-size and reduced-size liver transplantation in both rat and mouse has been successfully established. Because of the difficulties and complexities in microsurgical technology, the animal model of dual liver transplantation was still not established for twelve years since the first human dual liver transplantation has been made a success. There is an essential need to establish this animal model to lay a basic foundation for clinical practice. To study the physiological and histopathological changes of dual liver transplantation, "Y" type vein from the cross part between vena cava and two iliac of donor and "Y' type prosthesis were employed to recanalize portal vein and the bile duct between dual liver grafts and recipient. The dual right upper lobes about 45-50% of the recipient liver volume were taken as donor, one was orthotopically implanted at its original position, the other was rotated 180° sagitally and heterotopically positioned in the left upper quadrant. Microcirculation parameters, liver function, immunohistochemistry and survival were analyzed to evaluate the function of dual liver grafts. No significant difference in the hepatic microcirculatory flow was found between two grafts in the first 90 minutes after reperfusion. Light and electronic microscope showed the liver architecture was maintained without obvious features of cellular destruction and the continuity of the endothelium was preserved. Only 3 heterotopically positioned graft appeared patchy desquamation of endothelial cell, mitochondrial swelling and hepatocytes cytoplasmic vacuolization. Immunohistochemistry revealed there is no difference in hepatocyte activity and the ability of endothelia to contract and relax after reperfusion between dual grafts. Dual grafts made a rapid amelioration of liver function after reperfusion. 7 rats survived more than 7 days with survival rate of 58.3.%. Using "Y" type vein and bile duct prosthesis, we successfully established a novel rat model of dual right upper liver lobe transplantation.

Thymosin alpha1- and ulinastatin-based immunomodulatory strategy for sepsis arising from intra-abdominal infection due to carbapenem-resistant bacteria.

OBJECTIVE: The aim of this study was to evaluate the potential efficacy of therapy with thymosin alpha(1) and ulinastatin for patients with sepsis due to carbapenem-resistant bacteria. DESIGN: Prospective, randomized, parallel controlled clinical study. METHODS: A total of 120 patients received a diagnosis of sepsis caused by infection with carbapenem-resistant bacteria and satisfied the study enrollment criteria. Sixty patients received carbapenems combined with thymosin alpha(1) and ulinastatin (the CTU group), and the other 60 patients were treated with carbapenems and placebo (the CP group). For both groups, flow cytometry was used to enumerate lymphocyte subsets, and ELISA was used to determine cytokine concentrations. RESULTS: When the 2 groups were compared, the CTU group exhibited a better performance with respect to organ failure scores such as the Acute Physiology and Chronic Health Evaluation II score, the Multiple Organ Failure Score, and the Glasgow Coma Scale. The CTU group also showed significant improvements in CD4(+)CD8(+) count after initiation of treatment. In addition, compared with the CP group, in the CTU group the balance between proinflammatory mediators (such as tumor necrosis factor-alpha, interleukin [IL]-1beta, IL-6, and IL-8) and anti-inflammatory cytokines (including IL-4 and IL-10) was better modulated, and the cumulative survival rate of the CTU group exceeded that of the CP group by 17.8% at day 28, 25.9% at day 60, and 27.4% at day 90. CONCLUSION: Immunomodulatory therapy that combines thymosin alpha(1) and ulinastatin appears to improve the survival rate for patients infected with carbapenem-resistant bacteria. The number of patients in this study was relatively small, and although the same number of patients was initially enrolled in each study group, the groups were not the same size at the end of the study. Therefore, a larger clinical trial should be conducted to validate this conclusion. TRIAL REGISTRATION: The trial was registered with the Chinese State Food and Drug Administration (Peking Science and Technology Development Plan, 2002[641]), (registration number 2007Y0211).

Role of contrast CT in acute lower gastrointestinal bleeding.

OBJECTIVE: To evaluate the role of CT abdomen in the localization of acute lower gastrointestinal bleeding. SUMMARY BACKGROUND DATA: The source of bleed in acute lower gastrointestinal bleeding is often difficult to localize. The role of CT in the evaluation of this group of patients has not been clearly addressed. METHODS: A retrospective review of all patients with acute lower gastrointestinal bleeding over a 3-year period was carried out. When endoscopy failed to localize the source and bleeding continued, angiography and/or scintigraphy were carried out. In contrast, those who had normal endoscopies and had clinically stopped bleeding, underwent CT abdomen. RESULTS: CT done in 7 patients with no evidence of active bleed identified a lesion in 6 (86%). CONCLUSIONS: CT may be useful in acute lower gastrointestinal bleeding where endoscopy fails to localize a lesion and bleeding has stopped temporarily.