Immunological mechanisms of fecal microbiota transplantation in recurrent Clostridioides difficile infection

Fecal microbiota transplantation (FMT) is a successful method for treating recurrent Clostridioides difficile (C. difficile) infection (rCDI) with around 90% efficacy. Due to the relative simplicity of this approach, it is being widely used and currently, thousands of patients have been treated with FMT worldwide. Nonetheless, the mechanisms underlying its effects are just beginning to be understood. Data indicate that FMT effectiveness is due to a combination of microbiological direct mechanisms against C. difficile, but also through indirect mechanisms including the production of microbiota-derived metabolites as secondary bile acids and short chain fatty acids. Moreover, the modulation of the strong inflammatory response triggered by C. difficile after FMT seems to rely on a pivotal role of regulatory T cells, which would be responsible for the reduction of several cells and soluble inflammatory mediators, ensuing normalization of the intestinal mucosal immune system. In this minireview, we analyze recent advances in these immunological aspects associated with the efficacy of FMT.     

The role of serotonin within the microbiota-gut-brain axis in the development of Alzheimer’s disease: A narrative review

Alzheimer’s disease (AD) is the most common cause of dementia, accounting for more than 50 million patients worldwide. Current evidence suggests the exact mechanism behind this devastating disease to be of multifactorial origin, which seriously complicates the quest for an effective disease-modifying therapy, as well as impedes the search for strategic preventative measures. Of interest, preclinical studies point to serotonergic alterations, either induced via selective serotonin reuptake inhibitors or serotonin receptor (ant)agonists, in mitigating AD brain neuropathology next to its clinical symptoms, the latter being supported by a handful of human intervention trials. Additionally, a substantial amount of preclinical trials highlight the potential of diet, fecal microbiota transplantations, as well as pre- and probiotics in modulating the brain’s serotonergic neurotransmitter system, starting from the gut. Whether such interventions could truly prevent, reverse or slow down AD progression likewise, should be initially tested in preclinical studies with AD mouse models, including sufficient analytical measurements both in gut and brain. Thereafter, its potential therapeutic effect could be confirmed in rigorously randomized controlled trials in humans, preferentially across the Alzheimer’s continuum, but especially from the prodromal up to the mild stages, where both high adherence to such therapies, as well as sufficient room for noticeable enhancement are feasible still. In the end, such studies might aid in the development of a comprehensive approach to tackle this complex multifactorial disease, since serotonin and its derivatives across the microbiota-gut-brain axis might serve as possible biomarkers of disease progression, next to forming a valuable target in AD drug development. In this narrative review, the available evidence concerning the orchestrating role of serotonin within the microbiota-gut-brain axis in the development of AD is summarized and discussed, and general considerations for future studies are highlighted.     

肠道菌群与中药及其有效组分相互作用治疗消化系统疾病的研究进展＊

肠道菌群作为药物代谢的重要媒介，被认为是人体的又一器官，其在消化系统疾病发生、发展中所起到的重要价值已经得到学术界的公认，近五年来，从肠道菌群的角度出发，人们对中药及其有效组分治疗消化系统疾病的作用机制研究取得了一定成就，本研究将对这些成果进行归纳、总结。     

从脾论治慢性肾脏病的生物学基础探讨

脾为后天之源,肾为先天之本,以后天滋先天,使从脾论治成为中医临床治疗慢性肾脏病(CKD)的经典方法。现代医学研究发现人体内最庞大的“器官”——肠道菌群与“脾”的功能非常密切。目前研究发现肠道菌群紊乱是加速CKD进展的重要环节,基于脾肾互根互用的中医原理,收集、整理肠道菌群与CKD代谢功能、免疫应答及肾脏损伤关联的文献,从肠道菌群与机体功能代谢和内环境稳态的角度进行探讨,认识到运用中医药可通过干预肠道菌群的丰度、结构和代谢功能,维持肠道微生态的平衡,从而达到调节肾脏代谢和免疫应答的作用,提出肠道菌群是从脾论治慢性肾脏病的重要生物学基础。     

补肾化浊方联合粪菌移植对来曲唑诱导的多囊卵巢综合征大鼠生殖、代谢功能及相关炎症因子的影响

目的以肠道微生态为切入点探讨补肾化浊方联合粪菌移植治疗多囊卵巢综合征(PCOS)潜在机制。方法将30只6周龄SD大鼠随机分为空白组、模型组、中药组、粪菌移植组、中药+粪菌移植组,每组6只。来曲唑1 mg/(kg d)灌胃51 d,第22日起,中药组加灌补肾化浊方21.7 g/(kg d),粪菌移植组加灌新鲜粪便2 g/(kg d),中药+粪菌移植组加灌补肾化浊方21.7 g/(kg d)和新鲜粪便2 g/(kg d),连续30 d,另设空白组。干预结束后,腹主动脉取血检测大鼠血清性激素、空腹胰岛素(FINS)、空腹血糖(FPG),ELISA检测大鼠血清白细胞介素(IL)-18、肿瘤坏死因子-α(TNF-α)水平,HE染色观察大鼠卵巢形态学变化。结果与空白组比较,模型组大鼠卵巢呈多囊样改变,体质量、睾酮、黄体生成素(LH)/促卵泡激素(FSH)、FPG、HOMA-IR、IL-18、TNF-α水平均明显升高(P<0.01,P<0.001);与模型组比较,中药+粪菌移植组可显著改善上述指标(P<0.05,P<0.01,P<0.001),中药组可显著改善除TNF-α外各项指标(P<0.05,P<0.01),粪菌移植组可显著降低PCOS大鼠LH/FSH、IL-18水平(P<0.01,P<0.001);在降低IL-18水平方面,中药+粪菌移植组作用显著优于中药组(P<0.01)。结论中药联合粪菌移植可显著改善PCOS大鼠生殖和代谢功能,改善慢性炎症状态。     

Prospects for clinical applications of butyrate-producing bacteria

As the major source of energy for colonic mucosal cells and as an important regulator of gene expression, inflammation, differentiation, and apoptosis in host cells, microbiota-derived butyrate can enhance the intestinal mucosal immune barrier, modulate systemic immune response, and prevent infections. Maintaining a certain level of butyrate production in the gut can help balance intestinal microbiota, regulate host immune response, and promote the development and maintenance of the intestinal mucosal barrier. Butyrate-producing bacteria act as probiotics and play important roles in a variety of normal biological functions. Bacteriotherapeutic supplementation by using fecal microbiota transplantation to restore butyrate-producing commensal bacteria in the gut has been very successful in the treatment of recurrent and refractory Clostridium difficile (C. difficile) infection or C. difficile-negative nosocomial diarrhea. Administration of probiotics that include butyrate-producing bacteria may have a role in the treatment of inflammatory bowel diseases and in the prevention of necrotizing enterocolitis and late-onset sepsis in premature infants. Furthermore, modulating gut microbiota with dietary approaches may improve intestinal dysbiosis commonly seen in patients with obesity-associated metabolic disorders. Supplementation with a butyrate-producing bacterial stain might be used to increase energy expenditure, improve insulin sensitivity, and to help control obesity and metabolic syndrome.     

Hippuric acid: Could became a barometer for frailty and geriatric syndromes?

Aging is a natural biological event that has some downsides such as increased frailty, decline in cognitive and physical functions leading to chronical diseases, and lower quality of life. There is therefore a pressing need of reliable biomarkers to identify populations at risk of developing age-associated syndromes in order to improve their quality of life, promote healthy ageing and a more appropriate clinical management, when needed. Here we discuss the importance of hippuric acid, an endogenous co-metabolite, as a possible hallmark of human aging and age-related diseases, summarizing the scientific literature over the last years. Hippuric acid, the glycine conjugate of benzoic acid, derives from the catabolism by means of intestinal microflora of dietary polyphenols found in plant-based foods (e.g. fruits, vegetables, tea and coffee). In healthy conditions hippuric acid levels in blood and/or urine rise significantly during aging while its excretion drops in conditions related with aging, including cognitive impairments, rheumatic diseases, sarcopenia and hypomobility. This literature highlights the utility of hippuric acid in urine and plasma as a plausible hallmark of frailty, related to low fruit and vegetable intake and changes in gut microflora.