scholarly journals Fecal microbiota transplantation in HIV: A pilot placebo-controlled study

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sergio Serrano-Villar ◽  
Alba Talavera-Rodríguez ◽  
María José Gosalbes ◽  
Nadia Madrid ◽  
José A. Pérez-Molina ◽  
...  

AbstractChanges in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor’s microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2112
Author(s):  
Talía Sainz ◽  
María José Gosalbes ◽  
Alba Talavera ◽  
Nuria Jimenez-Hernandez ◽  
Luis Prieto ◽  
...  

Aims: The gut microbiota exerts a critical influence in the immune system. The gut microbiota of human virus immunodeficiency (HIV)-infected children remains barely explored. We aimed to characterize the fecal microbiota in vertically HIV-infected children and to explore the effects of its modulation with a symbiotic nutritional intervention. Methods: a pilot, double blind, randomized placebo-controlled study including HIV-infected children who were randomized to receive a nutritional supplementation including prebiotics and probiotics or placebo for four weeks. HIV-uninfected siblings were recruited as controls. The V3–V4 region of the 16S rRNA gene was sequenced in fecal samples. Results: 22 HIV-infected children on antiretroviral therapy (ART) and with viral load (VL) <50/mL completed the follow-up period. Mean age was 11.4 ± 3.4 years, eight (32%) were male. Their microbiota showed reduced alpha diversity compared to controls and distinct beta diversity at the genus level (Adonis p = 0.042). Patients showed decreased abundance of commensals Faecalibacterium and an increase in Prevotella, Akkermansia and Escherichia. The nutritional intervention shaped the microbiota towards the control group, without a clear directionality. Conclusions: Vertical HIV infection is characterized by changes in gut microbiota structure, distinct at the compositional level from the findings reported in adults. A short nutritional intervention attenuated bacterial dysbiosis, without clear changes at the community level. Summary: In a group of 24 vertically HIV-infected children, in comparison to 11 uninfected controls, intestinal dysbiosis was observed despite effective ART. Although not fully effective to restore the microbiota, a short intervention with pre/probiotics attenuated bacterial dysbiosis.


2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Alessandra Oliva ◽  
Lucia Aversano ◽  
Massimiliano De Angelis ◽  
Maria Teresa Mascellino ◽  
Maria Claudia Miele ◽  
...  

Abstract Background Clostridioides difficile infection (CDI) might be complicated by the development of nosocomial bloodstream infection (n-BSI). Based on the hypothesis that alteration of the normal gut integrity is present during CDI, we evaluated markers of microbial translocation, inflammation, and intestinal damage in patients with CDI. Methods Patients with documented CDI were enrolled in the study. For each subject, plasma samples were collected at T0 and T1 (before and after CDI therapy, respectively), and the following markers were evaluated: lipopolysaccharide-binding protein (LPB), EndoCab IgM, interleukin-6, intestinal fatty acid binding protein (I-FABP). Samples from nonhospitalized healthy controls were also included. The study population was divided into BSI+/BSI- and fecal microbiota transplantation (FMT) +/FMT- groups, according to the development of n-BSI and the receipt of FMT, respectively. Results Overall, 45 subjects were included; 8 (17.7%) developed primary n-BSI. Markers of microbial translocation and intestinal damage significantly decreased between T0 and T1, however, without reaching values similar to controls (P &lt; .0001). Compared with BSI-, a persistent high level of microbial translocation in the BSI+ group was observed. In the FMT+ group, markers of microbial translocation and inflammation at T1 tended to reach control values. Conclusions CDI is associated with high levels of microbial translocation, inflammation, and intestinal damage, which are still present at clinical resolution of CDI. The role of residual mucosal perturbation and persistence of intestinal cell damage in the development of n-BSI following CDI, as well as the possible effect of FMT in the restoration of mucosal integrity, should be further investigated.


Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 741
Author(s):  
Christophe Barba ◽  
Christophe O. Soulage ◽  
Gianvito Caggiano ◽  
Griet Glorieux ◽  
Denis Fouque ◽  
...  

Background: Chronic kidney disease (CKD) is a renal disorder characterized by the accumulation of uremic toxins with limited strategies to reduce their concentrations. A large amount of data supports the pivotal role of intestinal microbiota in CKD complications and as a major source of uremic toxins production. Here, we explored whether fecal microbiota transplantation (FMT) could be attenuated in metabolic complication and uremic toxin accumulation in mice with CKD. Methods: Kidney failure was chemically induced by a diet containing 0.25% (w/w) of adenine for four weeks. Mice were randomized into three groups: control, CKD and CKD + FMT groups. After four weeks, CKD mice underwent fecal microbiota transplantation (FMT) from healthy mice or phosphate buffered saline as control. The gut microbiota structure, uremic toxins plasmatic concentrations, and metabolic profiles were explored three weeks after transplantation. Results: Associated with the increase of alpha diversity, we observed a noticeable improvement of gut microbiota disturbance, after FMT treatment. FMT further decreased p-cresyl sulfate accumulation and improved glucose tolerance. There was no change in kidney function. Conclusions: These data indicate that FMT limited the accumulation of uremic toxins issued from intestinal cresol pathway by a beneficial effect on gut microbiota diversity. Further studies are needed to investigate the FMT efficiency, the timing and feces amount for the transplantation before, to become a therapeutic option in CKD patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zeyu Zhao ◽  
Zhengchang Guo ◽  
Zhengliang Yin ◽  
Yue Qiu ◽  
Bo Zhou

Background: Intestinal damage caused by intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) can lead to the ectopic gut microbiota, which can contribute to liver injury via portal veins. Therefore, it is speculated that gut microbiota disorder caused by IAH/ACS may result in liver injury. The relationship between gut microbiota and IAH/ACS-related liver injury was investigated in this study.Methods: A model of IAH was established in rats, and 16S rRNA sequencing was analyzed for gut microbiota in the feces of rats. The elimination of gut microbiota was completed by antibiotics gavage, and fecal microbiota transplantation (FMT) was used to change the composition of gut microbiota in rats.Results: In addition to the traditional cause of liver blood vessel compression, liver injury caused by IAH was also associated with gut microbiota dysbiosis. Gut microbiota clearance can relieve liver injury caused by IAH, while FMT from IAH-intervened rats can aggravate IAH-related liver injury.Conclusion: The gut microbiota was one of the most important factors contributing to the IAH-related liver injury, and the JNK/p38 signaling pathway was activated in this process.


Animals ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 93
Author(s):  
Siyu Chen ◽  
Shuyan Luo ◽  
Chao Yan

In the past few decades, farm animal health and welfare have been paid increasing concern worldwide. Farm animal health and welfare are generally assessed by the measurements of physical health, immune response, behavior, and physiological indicators. The gut microbiota has been reported to have a great influence on host phenotypes, possibly via the immune processes, neural functions, and endocrine pathways, thereby influencing host phenotypes. However, there are few reviews regarding farm animals’ health and welfare status concerning the gut microbiota. In this point of view, (1) we reviewed recent studies showing that gut microbiota (higher alpha diversity, beneficial composition, and positive functions) effectively influenced health characteristics, immunity, behaviors, and stress response in farm animals (such as pigs, chickens, and cows), which would provide a novel approach to measure and evaluate the health status and welfare of farm animals. In addition, fecal microbiota transplantation (FMT) as one of the methods can modulate the recipient individual’s gut microbiota to realize the expected phenotype. Further, (2) we highlighted the application of FMT on the improvement of the production performance, the reduction in disease and abnormal behavior, as well as the attenuation of stress in farm animals. It is concluded that the gut microbiota can be scientifically used to assess and improve the welfare of farm animals. Moreover, FMT may be a helpful strategy to reduce abnormal behavior and improve stress adaption, as well as the treatment of disease for farm animals. This review suggests that gut microbiota is a promising field to evaluate and improve animal welfare.


2020 ◽  
Vol 64 (1) ◽  
Author(s):  
Elvira Anna Carbone ◽  
Pasquale D'Amato ◽  
Giuseppe Vicchio ◽  
Pasquale De Fazio ◽  
Cristina Segura-Garcia

Abstract Background There is growing interest in new factors contributing to the genesis of eating disorders (EDs). Research recently focused on the study of microbiota. Dysbiosis, associated with a specific genetic susceptibility, may contribute to the development of anorexia nervosa (AN), bulimia nervosa, or binge eating disorder, and several putative mechanisms have already been identified. Diet seems to have an impact not only on modification of the gut microbiota, facilitating dysbiosis, but also on its recovery in patients with EDs. Methods This systematic review based on the PICO strategy searching into PubMed, EMBASE, PsychINFO, and Cochrane Library examined the literature on the role of altered microbiota in the pathogenesis and treatment of EDs. Results Sixteen studies were included, mostly regarding AN. Alpha diversity and short-chain fatty acid (SCFA) levels were lower in patients with AN, and affective symptoms and ED psychopathology seem related to changes in gut microbiota. Microbiota-derived proteins stimulated the autoimmune system, altering neuroendocrine control of mood and satiety in EDs. Microbial richness increased in AN after weight regain on fecal microbiota transplantation. Conclusions Microbiota homeostasis seems essential for a healthy communication network between gut and brain. Dysbiosis may promote intestinal inflammation, alter gut permeability, and trigger immune reactions in the hunger/satiety regulation center contributing to the pathophysiological development of EDs. A restored microbial balance may be a possible treatment target for EDs. A better and more in-depth characterization of gut microbiota and gut–brain crosstalk is required. Future studies may deepen the therapeutic and preventive role of microbiota in EDs.


2021 ◽  
Author(s):  
Luyun Fan ◽  
Jie Ren ◽  
Youren Chen ◽  
Yang Wang ◽  
Zihong Guo ◽  
...  

Abstract BackgroundHypertension is in current the leading modifiable cause of global morbidity and mortality, contributing to substantial health and financial burdens. Although multiple explorations on management models and innovative therapeutic strategies of hypertension, vacancy still occur in the field with poor control rate reflected and lacking of novel, effectively clinical-translated medication or intervention options. Recent animal and human studies repeatedly confirmed a link between microbiota and hypertension. Of note is our previous study establishing a cause-and-effect relationship between gut microbiota and blood pressure elevation. A hypothesis of gut microbiota intervention on treating hypertension is thus postulated with fecal microbiota transplantation(FMT) from healthy donors performed. MethodsA multi-center, central randomized, placebo-controlled, double-blinded clinical trial is performed in 120 grade 1 hypertensive patients for overall three months. All recruited patients will be randomly assigned in a 1:1 ratio into orally-taken FMT capsules or placebo capsules with three interventions on day 1, day 7 and day 14 in separate, and followed up on day 30, day 60 and day 90. The primary outcome is the change for office systolic blood pressure from baseline to day 30 follow-up. Main secondary outcomes are BP indicators including changes in systolic and diastolic blood pressure from office, home, and 24-hour ambulatory blood pressure monitoring, assessments of ankle-branchial index and pulse wave velocity, profiling of fecal microbial composition and function, profiling of fecal and serum metabolome, changes in levels of blood glucose, blood lipids and body mass index, assessment of adverse events as a measure of safety. DiscussionStretching from our previous research on the role of gut microbiota in the pathogenesis of hypertension, this study serves as a clinical translation advancement and firstly explores the potential of fecal microbiota transplantation on treating hypertension. Underlying mechanisms particularly on anchoring specific microorganisms or their postbiotics contributing to blood pressure amelioration will also be investigated via multiple approaches such as metagenomic sequencing and metabolomic profiling.Trial registrationClinicalTrials.gov Identifier: NCT04406129, registried on May 28th, 2020, https://clinicaltrials.gov/ct2/show/NCT04406129


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Elaine Wei-Yin Yu ◽  
Gao Liu ◽  
Petr Stastka ◽  
Michael Chadwick Cheney ◽  
Jasmin Mahabamunuge ◽  
...  

Abstract Background: There is intense interest about the therapeutic potential of altering gut microbiota to improve metabolism, based primarily on intriguing animal studies. One prior trial of fecal microbiota transplantation (FMT) in obese men found that improved metabolic response after FMT was predicted by low baseline microbiome diversity. In the current trial, we investigated the safety and efficacy of weekly oral FMT capsules to improve glycemic outcomes in obese adults, and also explored determinants of successful microbiome engraftment and metabolic improvement after FMT. Methods: FMT-TRIM was a double-blind randomized placebo-controlled pilot trial of weekly oral FMT vs placebo capsules for 6 weeks in 24 obese adults with mild-moderate insulin resistance. Each participant in the FMT arm received capsules derived from one of 4 metabolically healthy lean donors (BMI 18.5-23 kg/m2). The primary outcome was change in insulin sensitivity assessed by hyperinsulinemic euglycemic clamp at 0 and 6 weeks. Secondary outcomes included body weight, metabolic labs, and body composition assessed by DXA over 12 weeks. 16SV4 rRNA sequencing was performed to assess microbiome composition and engraftment. Post-hoc exploratory analyses investigated metabolic outcomes after stratification by baseline microbiome diversity. Results: FMT and placebo groups were well balanced in terms of age (mean±SD 40±9 yrs), BMI (40±6 kg/m2), sex (72% female), and baseline metabolic measures. During the study, there were no statistically significant differences in insulin sensitivity between the FMT and placebo groups (+5 ± 12% FMT vs -3 ± 32% placebo, mean percent difference 9%, 95% CI -5% to 28%; p=0.16). There was a minor improvement in HbA1c at 12 weeks after FMT as compared to placebo (mean difference -0.1, 95% CI -0.3-0.01), but no significant differences in other metabolic labs, body weight, or body composition. Microbial engraftment varied by donor but was present in most FMT recipients, with persistence of engrafting strains throughout the 12-week study. Subgroup analyses of subjects with low microbiome diversity at baseline (FMT n=4, placebo n=7) showed a relative benefit of FMT over placebo at 12 weeks for HbA1c (mean difference -0.2, 95% CI -0.4 to -0.01), total cholesterol (-22 mg/dL, 95% CI -40 to -4 mg/dL), and fasting glucose (-10 mg/dL, 95% CI -19 to -1 mg/dL). There were no significant differences in adverse events between FMT and placebo groups. Conclusion: Weekly administration of FMT capsules results in gut microbiota engraftment for at least 12 weeks but does not meaningfully alter human metabolism in an unselected population of obese adults. Future studies are needed to elucidate the role of baseline recipient microbial diversity and other factors on the impact of FMT.


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