Feasibility of fecal microbiota transplantation via oral gavage to safely alter gut microbiome composition in marmosets

Disruption of microbial communities within human hosts has been associated with infection, obesity, cognitive decline, cancer risk and frailty, suggesting that microbiome-targeted therapies may be an option for improving healthspan and lifespan. The objectives of this study were to determine the feasibility of delivering fecal microbiota transplants (FMTs) to marmosets via oral gavage and to evaluate if alteration of the gut microbiome post-FMT could be achieved. This was a prospective study of marmosets housed at the Barshop Institute for Longevity and Aging Studies in San Antonio, Texas. Eligible animals included healthy young adult males (age 2–5 years) with no recent medication use. Stool from two donors was combined and administered in 0.5 ml doses to five young recipients once weekly for 3 weeks. Safety outcomes and alterations in the gut microbiome composition via 16S ribosomal RNA sequencing were compared at baseline and monthly up to 6 months post-FMT. Overall, significant differences in the percent relative abundance was seen in FMT recipients at the phylum and family levels from baseline to 1 month and baseline to 6 months post-FMT. In permutational multivariate analysis of variance analyses, treatment status (donor vs. recipient) (p = .056) and time course (p = .019) predicted β diversity (p = .056). The FMT recipients did not experience any negative health outcomes over the course of the treatment. FMT via oral gavage was safe to administer to young adult marmosets. The marmoset microbiome may be altered by FMT; however, progressive changes in the microbiome are strongly driven by the host and its baseline microbiome composition.     

Transplantation of engineered bone tissue using a rotary three-dimensional culture system

Bone is a complex, highly structured, mechanically active, three-dimensional (3-D) tissue composed of cellular and matrix elements. We previously published a report on in situ collagen gelation using a rotary 3-D culture system (CG–RC system) for the construction of large tissue specimens. The objective of the current study was to evaluate the feasibility of bone tissue engineering using our CG–RC system. Osteoblasts from the calvaria of newborn Wistar rats were cultured in the CG–RC system for up to 3 wk. The engineered 3-D tissues were implanted into the backs of nude mice and calvarial round bone defects in Wistar rats. Cell metabolic activity, mineralization, and bone-related proteins were measured in vitro in the engineered 3-D tissues. Also, the in vivo histological features of the transplanted, engineered 3-D tissues were evaluated in the animal models. We found that metabolic activity increased in the engineered 3-D tissues during cultivation, and that sufficient mineralization occurred during the 3 wk in the CG–RC system in vitro. One mo posttransplantation, the transplants to nude mice remained mineralized and were well invaded by host vasculature. Of particular interest, 2 mo posttransplantation, the transplants into the calvarial bone defects of rats were replaced by new mature bone. Thus, this study shows that large 3-D osseous tissue could be produced in vitro and that the engineered 3-D tissue had in vivo osteoinductive potential when transplanted into ectopic locations and into bone defects. Therefore, this system should be a useful model for bone tissue engineering.     

Treatment of long tubular bone defect of rabbit using autologous cultured osteoblasts mixed with fibrin

The osteogenic potential of autologous cultured osteoblasts mixed with fibrin when transplanted to bone defects was evaluated. Radial shaft defects over 15 mm were made in 30 New Zealand white rabbits. A total of 15 rabbits in the control group underwent an iliac bone graft and 15 rabbits in the experimental group underwent an autologous cultured osteoblast injection mixed with fibrin. Both groups were compared radiologically and 5 rabbits in each group were sacrificed for histological evaluation using H-E and Masson’s trichrome stain at 3, 6, and 9 weeks. Osteogenesis in the control group progressed more rapidly than in the experimental group. However, at 9 weeks, bone formation in both groups were similar and showed no significant difference in terms of the amount of bone formation and the quality of bone union. Autologous cultured osteoblast transplantation mixed with fibrin in bone defects was found to produce bone efficiently.     

Ethics and Rationing Access to Dialysis in Resource‐Limited Settings: The Consequences of Refusing a Renal Transplant in the South African State Sector

Resource constraints in developing countries compel policy makers to ration the provision of healthcare services. This article examines one such set of Guidelines: A patient dialysing in the state sector in South Africa may not refuse renal transplantation when a kidney becomes available. Refusal of transplantation can lead to exclusion from the state‐funded dialysis programme. This Guideline is legally acceptable as related to Constitutional stipulations which allow for rationing healthcare resources in South Africa. Evaluating the ethical merit of the Guideline, and exploring the ethical dilemma it poses, proves a more complex task. We examine the actions of healthcare professionals as constrained by the Guideline. From a best interests framework, we argue that in these circumstances directing patient decision making (pressurising a patient to undergo renal transplantation) is not necessarily unethical or unacceptably paternalistic. We then scrutinise the guideline itself through several different ethical ‘lenses’. Here, we argue that bioethics does not provide a definitive answer as to the moral merit of rationing dialysis under these circumstances, however it can be considered just in this context. We conclude by examining a potential pitfall of the Guideline: Unwilling transplant recipients may not comply with immunosuppressive medication, which raises questions for policies based on resource management and rationing.     

Systemic transplantation of human adipose-derived stem cells stimulates bone repair by promoting osteoblast and osteoclast function

Systemic transplantation of adipose-derived stem cells (ASCs) is emerging as a novel therapeutic option for functional recovery of diverse damaged tissues. This study investigated the effects of systemic transplantation of human ASCs (hASCs) on bone repair. We found that hASCs secrete various bone cell-activating factors, including hepatocyte growth factor and extracellular matrix proteins. Systemic transplantation of hASCs into ovariectomized mice induced an increased number of both osteoblasts and osteoclasts in bone tissue and thereby prevented bone loss. We also observed that conditioned medium from hASCs is capable of stimulating proliferation and differentiation of osteoblasts via Smad/extracellular signal-regulated kinase (ERK)/JNK (c-jun NH(2) -terminal kinase) activation as well as survival and differentiation of osteoclasts via ERK/JNK/p38 activation in vitro. Overall, our findings suggest that paracrine factors secreted from hASCs improve bone repair and that hASCs can be a valuable tool for use in osteoporosis therapy.     

Bone marrow‐derived cells can acquire cardiac stem cells properties in damaged heart

Experimental data suggest that cell‐based therapies may be useful for cardiac regeneration following ischaemic heart disease. Bone marrow (BM) cells have been reported to contribute to tissue repair after myocardial infarction (MI) by a variety of humoural and cellular mechanisms. However, there is no direct evidence, so far, that BM cells can generate cardiac stem cells (CSCs). To investigate whether BM cells contribute to repopulate the Kit⁺ CSCs pool, we transplanted BM cells from transgenic mice, expressing green fluorescent protein under the control of Kit regulatory elements, into wild‐type irradiated recipients. Following haematological reconstitution and MI, CSCs were cultured from cardiac explants to generate ‘cardiospheres’, a microtissue normally originating in vitro from CSCs. These were all green fluorescent (i.e. BM derived) and contained cells capable of initiating differentiation into cells expressing the cardiac marker Nkx2.5. These findings indicate that, at least in conditions of local acute cardiac damage, BM cells can home into the heart and give rise to cells that share properties of resident Kit⁺ CSCs.     

粪菌移植治疗难治性肠易激综合征的效果观察

观察粪菌移植(FMT)对难治性肠易激综合征的治疗效果, 为该病的治疗提供参考。

招募我院32例难治性肠易激综合征患者并分为治疗组(n=17)和对照组(n=15), 两组患者均给予马来酸曲美布汀片口服, 治疗组进一步通过鼻肠管行FMT。分别于治疗1个月和3个月时评估两组患者临床疗效及安全性, 并严格记录不良反应。

治疗组患者FMT治疗前、治疗1个月和治疗3个月时IBS-SSS评分和粪便分型逐渐降低(均P < 0.05), 而对照组患者这3个时间点IBS-SSS评分和粪便分型差异无统计学意义(均P > 0.05)。FMT治疗前两组患者IBS-SSS评分和粪便分型差异无统计学意义(均P > 0.05)。治疗1个月和治疗3个月时, 两组患者IBS-SSS评分差异均有统计学意义(均P < 0.05)。治疗组患者FMT治疗前、治疗1个月和治疗3个月时IBS-QOL和HAD评分逐渐降低(均P < 0.05), 而对照组患者这3个时间点的IBS-QOL和HAD评分差异无统计学意义(均P > 0.05)。FMT治疗前, 两组患者IBS-QOL和HAD评分差异无统计学意义(均P > 0.05)。治疗1个月时两组患者IBS-QOL评分差异有统计学意义(P < 0.05), 而HAD评分差异无统计学意义(P > 0.05)。治疗3个月时两组患者IBS-QOL和HAD评分差异均有统计学意义(均P < 0.05)。治疗组患者症状缓解率高于对照组(88.2% vs 53.3%)。治疗3个月后两组患者均未出现明显不良反应且未发现传染性疾病。

FMT对难治性肠易激综合征有一定的临床疗效, 且安全可靠。

     

Heterogeneous impact of cytomegalovirus reactivation on nonrelapse mortality in hematopoietic stem cell transplantation

This study aims to retrospectively analyze the efficacy of penciclovir in the prevention of viral infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ninety-six patients with allo-HSCT were enrolled, who were treated at the Medical Center of Hematology of Xinqiao Hospital from June 2020 to September 2021. The experimental and control groups were treated with penciclovir and acyclovir, respectively, to prevent viral infection. By February 2022, the infection rates of cytomegalovirus, BK virus, JC virus, and Epstein-Barr virus (EBV) in the experimental group and the control group were 18.8% and 39.06% (P<0.05), 28.1% and 25% (P>0.05), 6.2% and 7.81% (P>0.05), 21.8% and 23.43% (P>0.05), respectively. The infection-related urinary system symptoms of the experimental group and the control group occurred in 4 and 9 patients, respectively, of which 3 and 9 patients died, respectively. Penciclovir can significantly reduce the cytomegalovirus infection rate after allo-HSCT and has better preventive effects than acyclovir without obvious side effects. The effectiveness and safety of penciclovir will be further verified in the future.     

粪菌移植研究的文献计量学和可视化分析

【背景】粪菌移植是近年医学领域研究的热点,不但能够治疗消化系统疾病,而且在神经及精神系统、心血管系统相关疾病的治疗中均有不错的疗效,有着广阔的应用前景。【目的】掌握国内外粪菌移植的研究现状、热点及发展趋势,为相关领域科研工作者的研究提供参考。【方法】基于Web of Science核心数据库,通过CiteSpace对2011-2021年的年度发文量、作者、国家、期刊、被引情况和关键词等进行可视化分析。【结果】筛选后共纳入4 905篇文献,目前全球粪菌移植研究的文献数量呈快速增长趋势;美国和中国是发文量最多的国家。中国学者的总发文量虽然位居世界第二,但中心度和篇均被引频次较低,说明受关注程度及学术影响力不足,在发文质量上还有待提高;Gastroenterology是国内外学者发文量最多的期刊,Frontiers in Microbiology是中国学者发文量最多的期刊;粪菌移植呈现出多学科交叉的发展特点;粪菌移植目前的研究热点主要与肠内疾病(炎症性肠病、艰难梭菌感染)和肠外疾病(如抑郁、冠状动脉粥样硬化等)有关;粪菌移植在未成年人中的应用、对胰岛素敏感度的影响、测序技术在肠道菌群的应用及...     

粪菌移植通过微生物-肠-脑轴改善抑郁症的研究进展

人类粪菌移植(fecal microbiota transplantation,FMT)早在19世纪50年代的西方医学中便有临床应用.FMT已被证明可以很好地缓解艰难梭菌感染(Clostridium difficile infection,CDI)的胃肠道疾病,在调节微生物-肠-脑轴(microbiota-gut-br...