Cytotoxic synergism of Clostridioides difficile toxin B with proinflammatory cytokines in subjects with inflammatory bowel diseases

Clostridioides difficile(C. difficile) is progressively colonizing humans and animals living with humans. During this process, hypervirulent strains and mutated toxin A and B of C. difficile(TcdA and TcdB) are originating and developing. While in healthy subjects colonization by C. difficile becomes a risk after the use of antibiotics that alter the microbiome, other categories of people are more susceptible to infection and at risk of relapse, such as those with inflammatory bowel disease(IBD)....     

Overview of current detection methods and microRNA potential in Clostridioides difficile infection screening

Clostridioides difficile (formerly called Clostridium difficile,C.difficile) infection (CDI)is listed as an urgent threat on the 2019 antibiotic resistance threats report in the United States by the Centers for Disease Control and Prevention.Early detection and appropriate disease management appear to be essential.Meanwhile,although the majority of cases are hospital-acquired CDI,community-acquired CDI cases are also on the rise,and this vulnerability is not limited to immunocompromised patients...     

Chinese physicians’ perceptions of fecal microbiota transplantation

AIM: To explore Chinese physicians’ perceptions towards fecal microbiota transplantation (FMT) and to provide information and an assessment of FMT development in China. METHODS: A self-administered questionnaire was developed according to the FMT practice guidelines and was distributed to physicians in hospitals via Internet Research Electronic Data Capture (REDcap) software and electronic mails to assess their attitudes toward and knowledge of FMT. The questionnaire included a brief introduction of FMT that was followed by 20 questions. The participants were required to respond voluntarily, under the condition of anonymity and without compensation. Except for the fill-in-the-blank questions, all of the other questions were required in the REDcap data collection systems, and the emailed questionnaires were completed based on eligibility. RESULTS: Up to December 9, 2014, 844 eligible questionnaires were received out of the 980 distributed questionnaires, with a response rate of 86.1%. Among the participants, 87.3% were from tertiary hospitals, and there were 647 (76.7%) gastroenterologists and 197 (23.3%) physicians in other departments (non-gastroenterologists). Gastroenterologists’ awareness of FMT prior to the survey was much higher than non-gastroenterologists’ (54.3 vs 16.5%, P < 0.001); however, acceptance of FMT was not statistically different (92.4 vs 87.1%, P = 0.1603). Major concerns of FMT included the following: acceptability to patients (79.2%), absence of guidelines (56.9%), and administration and ethics (46.5%). On the basis of understanding, the FMT indications preferred by physicians were recurrent Clostridium difficile infection (86.7%), inflammatory bowel disease combined with Clostridium difficile infection (78.6%), refractory ulcerative colitis (70.9%), ulcerative colitis (65.4%), Crohn’s disease (59.4%), chronic constipation (43.7%), irritable bowel syndrome (39.1%), obesity (28.1%) and type 2 diabetes (23.9%). For donor selection, the majority of physicians preferred individuals with a similar gut flora environment to the recipients. 76.6% of physicians chose lower gastrointestinal tract as the administration approach. 69.2% of physicians considered FMT a safe treatment. CONCLUSION: Chinese physicians have awareness and a high acceptance of FMT, especially gastroenterologists, which provides the grounds and conditions for the development of this novel treatment in China. Physicians’ greatest concerns were patient acceptability and absence of guidelines.     

Clostridioides difficile infection in patients with nonalcoholic fatty liver disease-current status

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, leading to fibrosis, cirrhosis and hepatocellular carcinoma and also associated with increased cardiovascular disease mortality. The pathogenesis of NAFLD is not fully understood, although NAFLD is thought to be a hepatic form of metabolic syndrome. There is an increasing understanding of the role of microbiota disturbances in NAFLD pathogenesis, and as with many other conditions affecting the microbiota, NAFLD may be a novel risk factor for Clostridioides difficile (C. difficile) colonization (CDC) and C. difficile infection (CDI). CDI is an emerging nosocomial disease, and community-acquired cases of infection are growing, probably due to an increase in CDC rates. The association of NAFLD with CDI has been shown in only 4 studies to date, three of which included less than 1000 patients, although the frequency of NAFLD in these studies was observed in almost 20% of the total patient cohort. These data revealed that NAFLD is a risk factor for CDI development and, moreover, is a risk factor for intestinal complications of CDI. More studies are needed to investigate this association and move forward CDC and CDI screening efforts for this group of patients.     

Frontiers in antibiotic alternatives for Clostridioides difficile infection

Clostridioides difficile (C. difficile) is a gram-positive, anaerobic spore-forming bacterium and a major cause of antibiotic-associated diarrhea. Humans are naturally resistant to C. difficile infection (CDI) owing to the protection provided by healthy gut microbiota. When the gut microbiota is disturbed, C. difficile can colonize, produce toxins, and manifest clinical symptoms, ranging from asymptomatic diarrhea and colitis to death. Despite the steady-if not rising-prevalence of CDI, it will certainly become more problematic in a world of antibiotic overuse and the post-antibiotic era. C. difficile is naturally resistant to most of the currently used antibiotics as it uses multiple resistance mechanisms. Therefore, current CDI treatment regimens are extremely limited to only a few antibiotics, which include vancomycin, fidaxomicin, and metronidazole. Therefore, one of the main challenges experienced by the scientific community is the development of alternative approaches to control and treat CDI. In this Frontier article, we collectively summarize recent advances in alternative treatment approaches for CDI. Over the past few years, several studies have reported on natural product-derived compounds, drug repurposing, high-throughput library screening, phage therapy, and fecal microbiota transplantation. We also include an update on vaccine development, pre- and pro-biotics for CDI, and toxin antidote approaches. These measures tackle CDI at every stage of disease pathology via multiple mechanisms. We also discuss the gaps and concerns in these developments. The next epidemic of CDI is not a matter of if but a matter of when. Therefore, being well-equipped with a collection of alternative therapeutics is necessary and should be prioritized.     

EMA-qPCR检测空肠弯曲活菌方法研究

目的 建立一种快速定量检测食品中“活的”空肠弯曲菌的技术方案。方法 通过对10³ CFU/m~10⁶ CFU/mL的空肠弯曲菌进行叠氮溴化乙锭(EMA)的前处理研究,建立区分死菌与活菌的EMA前处理技术,与荧光定量PCR检测弯曲菌的方法相结合,建立EMA-qPCR组合检测技术,并进行模拟食品标本的验证。结果 空肠弯曲菌在10³ CFU/mL~10⁶ CFU/mL内,EMA的最优使用浓度为5 μg/mL,5 μg/mL的EMA-qPCR可区分出死/活空肠弯曲菌混合物中的死菌和活菌,并成功应用于模拟食品标本中“活的”空肠弯曲菌的检测。结论 EMA-qPCR可作为快速定量检测样本中“活的”空肠弯曲菌的方法。     

Human immunodeficiency virus,atherosclerosis and Chlamydophila pneumoniae

Chlamydophila pneumoniae (C. pneumoniae) is an obligate, intracellular bacterium associated with a wide variety of acute and chronic diseases. C. pneumoniae infection is characterized by persistence and immunopathological damage to host target tissues, including the lung. Over the past 20 years, a variety of studies have investigated a possible link between C. pneumoniae infection and atherosclerosis, because of its role in all stages of atherosclerosis, from initial inflammatory lesions to plaque rupture. In the current highly active antiretroviral therapy (HAART) era, many human immunodeficiency virus (HIV)-infected patients are experiencing health problems that accompany the aging process, mainly the risk of cardiovascular disease (CVD). There is renewed interest in a link between atherosclerotic CVD and as yet poorly defined environmental exposures, including infectious agents. On the one hand, the patient with HIV and lipodystrophy caused by HAART and exacerbated by C. pneumoniae infection could be a factor of risk for atherosclerosis. An assessment of the therapy against C. pneumoniae and HAART should always be conducted. It is advisable that HIV-acquired immune deficiency syndrome patients undergo a serological test to determine exposure to C. pneumoniae and to assess treatment options. On the other hand, in patients with a positive serology to C. pneumoniae, an increment of the body mass index has been found; therefore, it is probable that the recurrent infection may play an important role in creating adverse endothelial conditions allowing the infection by C. pneumoniae in its chronic form, to damage the endothelial surface. Vascular studies would be necessary for corroboration.     

Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation

Ulcerative colitis(UC) is an inflammatory disease that mainly affects the colon and rectum. It is believed that genetic factors, host immune system disorders, intestinal microbiota dysbiosis, and environmental factors contribute to the pathogenesis of UC. however, studies on the role of intestinal microbiota in the pathogenesis of UC have been inconclusive. Studies have shown that probiotics improve intestinal mucosa barrier function and immune system function and promote secretion of anti-inflammatory factors, thereby inhibiting the growth of harmful bacteria in the intestine. Fecal microbiota transplantation(FMT) can reduce bowel permeability and thus the severity of disease by increasing the production of short-chain fatty acids, especially butyrate, which help maintain the integrity of the epithelial barrier. FMT can also restore immune dysbiosis by inhibiting Th1 differentiation, activity of T cells, leukocyte adhesion, and production of inflammatory factors. Probiotics and FMT are being increasingly used to treat UC, but their use is controversial because of uncertain efficacy. Here, we briefly review the role of intestinal microbiota in thepathogenesis and treatment of UC.     

一株猴源空肠弯曲菌的鉴定及其生物学特性分析

目的 对一株腹泻猴源的空肠弯曲菌分离株M166进行鉴定和生物学特性研究。方法 通过多重PCR、生化鉴定、MALDI-TOF-MS质谱鉴定、电镜观察等方法验证猴源分离株,通过与标准株NCTC11168进行比较,对生长曲线、运动力、Balb/c小鼠体内定殖实验等生物学特性进行研究。结果 该分离株多重PCR显示空肠弯曲菌阳性,马尿酸钠水解阳性,VITEK-2生化和MALDI-TOF-MS分析均鉴定为空肠弯曲菌,电镜观察显示为典型的弯曲菌形态;与NCTC11168相比,M166在MH液体培养基中的生长速度和增殖程度弱于NCTC11168,但运动力更为活跃;攻毒后第7 d小鼠体内定殖实验结果表明,NCTC11168攻毒组无细菌检出,而M166攻毒组能持续排菌,且在十二指肠、空肠、回肠、盲肠中定殖,每克载菌量分别可达3.09±0.47,3.01±0.84,3.80±0.46,5.63±0.34 CFU/g。结论 M166具有空肠弯曲菌典型的生物学特性,且在小鼠肠道中定殖能力强,这可能是M166能在实验猴体内定殖并导致腹泻的重要因素。     

Is there an unrecognised role for Campylobacter infections in (chronic) inflammatory diseases?

Campylobacter species are one of the major causes of global bacterial-related diarrheal disease worldwide. The disease is most frequently associated with the ingestion of contaminated meat, raw milk, pets, contaminated water, and the organism may be frequently cultured from the faeces of chicken and other domesticated farm animals. Of the 17 established Campylobacter species, the most important pathogens for humans are Campylobacter jejuni (C. jejuni), Campylobacter coli (C. coli) and Campylobacter fetus (C. fetus), which are all associated with diarrheal disease. Further, C. jejuni and C. coli are also associated with the neuroparalytic diseases Guillain-Barré syndrome and Miller Fischer syndrome, respectively, whereas C. fetus is linked with psoriatic arthritis. The discovery of both “molecular mimicry” and translocation-related virulence in the pathogenesis of C. jejuni-induced disease, indicates that Campylobacter-related gastrointestinal infections may not only generate localized, acute intestinal infection in the human host, but may also be involved in the establishment of chronic inflammatory diseases. Indeed, pathogenicity studies on several Campylobacter species now suggest that molecular mimicry and translocation-related virulence is not only related to C. jejuni, but may play a role in human disease caused by other Campylobacter spp. In this review, the authors provide a review based on the current literature describing the potential links between Campylobacter spp. and (chronic) inflammatory diseases, and provide their opinions on the likely role of Campylobacter in such diseases.     

Current Evidence for the Management of Inflammatory Bowel Diseases Using Fecal Microbiota Transplantation

Purpose of Review

Fecal microbiota transplantation (FMT) has been investigated as a potential treatment for inflammatory bowel disease (IBD). This review examines current evidence around the efficacy and safety of FMT for patients with IBD.

Recent Findings

Randomized controlled trials (RCTs) and meta-analyses have suggested that FMT may facilitate clinical and endoscopic remission in patients with active ulcerative colitis (UC). Although the evidence for FMT in Crohn’s disease (CD) is more limited, positive outcomes have been observed in small cohort studies. Most adverse events (AEs) were mild and included transient gastrointestinal symptoms. Serious adverse events (SAEs) did not differ significantly between the FMT and control groups, and a marginal increased rate of IBD flares following FMT was observed. Microbiota analysis following FMT showed increased intestinal bacterial diversity and a shift towards the donor microbial profile in recipients’ stools.

Summary

FMT for patients with IBD is promising as RCTs have shown the benefit of FMT for UC, although the efficacy of FMT for CD is less clear. Further large and well-designed trials are necessary to resolve critical issues such as the donor selection, the ideal route of administration, duration, frequency of FMT, and the long-term sustained efficacy and safety.

     

Neisseria gonorrhoeae and Chlamydia trachomatis infections in patients attending STD and family planning clinics in Bissau, Guinea-Bissau

Accurate clinical and laboratory data about sexually transmitted diseases (STD) prevalence in Guinea-Bissau are not available. These data are important, since HIV2 is prevalent in this country, rates of HIV1 are increasing and STDs facilitate HIV transmission. Since DNA amplification methods have demonstrated to accurately diagnose chlamydial infections and gonorrhoea, the Amplicor CT/NG PCR Assay with Internal Control of Amplification (Roche Diagnostic System, Branchburg, NJ, USA) was used to estimate the prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis genital infections in STDs and Family Planning Clinic attenders in Bissau, from March to July 1997. Two hundred and two cervical swabs and 31 urethral swabs were examined. Two women were excluded from this study because their cervical swabs contained inhibitory substances. N. gonorrhoeae was identified in 34/200 (17%) women and in 12/31 (38.7%) men. C. trachomatis was detected in 8/200 (4%) women there were no positive C. trachomatis results among the 31 men with urethritis. One woman presented a mixed infection with both organisms. The prevalence difference between men and women was not statistically significant (P=0.6) for C. trachomatis infection, but it was significant for N. gonorrhoeae infection (P=0.01). The prevalence rates of these infections found in this study, support the need for an urgent strategy to control STD in the region.     

Fecal microbiota transplantation for severe enterocolonic fistulizing Crohn’s disease

The concept of fecal microbiota transplantation(FMT)has been used in traditional Chinese medicine at least since the 4thcentury.Evidence from recent human studies strongly supports the link between intestinal bacteria and inflammatory bowel disease.We proposed that standardized FMT might be a promising rescue therapy for refractory inflammatory bowel disease.However,there were no reports of FMT used in patients with severe Crohn’s disease(CD).Here,we report the successful treatment of standardized FMT as a rescue therapy for a case of refractory CD complicated with fistula,residual Barium sulfate and formation of intraperitoneal large inflammatory mass.As far as we know,this is the first case of severe CD treated using FMT through mid-gut.     

Understanding the mechanisms of efficacy of fecal microbiota transplant in treating recurrent Clostridioides difficile infection and beyond: the contribution of gut microbial-derived metabolites

ABSTRACT

Fecal microbiota transplant (FMT) is a highly-effective therapy for recurrent Clostridioides difficile infection (rCDI), and shows promise for certain non-CDI indications. However, at present, its mechanisms of efficacy have remained poorly understood. Recent studies by our laboratory have noted the particular key importance of restoration of gut microbe-metabolite interactions in the ability of FMT to treat rCDI, including the impact of FMT upon short chain fatty acid (SCFAs) and bile acid metabolism. This includes a significant impact of these metabolites upon the life cycle of C. difficile directly, along with potential postulated additional benefits, including effects upon host immune response. In this Addendum, we first present an overview of these recent advancements in this field, and then describe additional novel data from our laboratory on the impact of FMT for rCDI upon several gut microbial-derived metabolites which had not previously been implicated as being of relevance.     

Effective fecal microbiota transplantation for recurrent Clostridioides difficile infection in humans is associated with increased signalling in the bile acid-farnesoid X receptor-fibroblast growth factor pathway

The mechanisms of efficacy for fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI) remain poorly defined, with restored gut microbiota-bile acid interactions representing one possible explanation. Furthermore, the potential implications for host physiology of these FMT-related changes in gut bile acid metabolism are also not well explored. In this study, we investigated the impact of FMT for rCDI upon signalling through the farnesoid X receptor (FXR)-fibroblast growth factor (FGF) pathway. Herein, we identify that in addition to restoration of gut microbiota and bile acid profiles, FMT for rCDI is accompanied by a significant, sustained increase in circulating levels of FGF19 and reduction in FGF21. These FGF changes were associated with weight gain post-FMT, to a level not exceeding the pre-rCDI baseline. Collectively, these data support the hypothesis that the restoration of gut microbial communities by FMT for rCDI is associated with an upregulated FXR-FGF pathway, and highlight the potential systemic effect of FMT.     

Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment

Gut microbiota constitute the largest reservoir of the human microbiome and are an abundant and stable ecosystem—based on its diversity, complexity, redundancy, and host interactions This ecosystem is indispensable for human development and health. The integrity of the intestinal mucosal barrier depends on its interactions with gut microbiota. The commensal bacterial community is implicated in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC). The dysbiosis of microbes is characterized by reduced biodiversity, abnormal composition of gut microbiota, altered spatial distribution, as well as interactions among microbiota, between different strains of microbiota, and with the host. The defects in microecology, with the related metabolic pathways and molecular mechanisms, play a critical role in the innate immunity of the intestinal mucosa in UC. Fecal microbiota transplantation (FMT) has been used to treat many diseases related to gut microbiota, with the most promising outcome reported in antibiotic‐associated diarrhea, followed by IBD. This review evaluated the results of various reports of FMT in UC. The efficacy of FMT remains highly controversial, and needs to be regularized by integrated management, standardization of procedures, and individualization of treatment.     

抗结核药物引起的艰难梭状芽胞杆菌相关性腹泻一例并文献复习

抗生素的使用是发生艰难梭状芽胞杆菌相关性腹泻的危险因素,而其中抗结核药物的使用则很少被报道与之相关。作者报告了1例与抗结核药物治疗相关的艰难梭状芽胞杆菌相关性腹泻患者,并搜集相关文献进行复习。患者为女性,32岁,罹患肺结核已行抗结核药物治疗9个月。因腹痛、腹泻入院治疗,通过艰难梭状芽胞杆菌毒素及谷氨酸脱氢酶检测呈阳性确诊。在停用抗结核药物,以及接受万古霉素和双歧杆菌乳杆菌三联活菌片(金双歧)治疗9d后症状缓解。作者通过复习相关文献,讨论了艰难梭状芽胞杆菌相关性腹泻的发病机制、临床表现、诊断和治疗方法,提醒临床医生了解结核病治疗过程中的罕见并发症,尽早确诊并采取必要的干预措施。     

Role of fecal microbiota transplantation in inflammatory bowel disease

There is increasing evidence of the key role played by altered intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD). Management strategies involving immune modulation are effective and widely used, but treatment failures and side effects occur. Fecal microbiota transplantation (FMT) provides a novel, perhaps complementary, strategy to restore the normal gut microbiota in patients with IBD. This review summarizes the available efficacy and safety data on the use of FMT in patients with IBD. Several aspects remain to be clarified about the clinical predictors of the response to FMT, its most appropriate route of administration, and the most appropriate quantity and quality of microbiota to be transplanted. Further studies focusing on long‐term outcomes and safety are also warranted.