scholarly journals Donor-dependent Fecal Microbiota Transplantation Efficacy Against Necrotizing Enterocolitis in Preterm Pigs

2020 ◽  
Author(s):  
Yan Hui ◽  
Gisle Alberg Vestergaard ◽  
Ling Deng ◽  
Witold Piotr Kot ◽  
Thomas Thymann ◽  
...  
Keyword(s):  
Necrotizing Enterocolitis ◽  
Fecal Microbiota Transplantation ◽  
Gastrointestinal Disease ◽  
Amplicon Sequencing ◽  
Rectal Administration ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Shotgun Metagenomics ◽  
Pathological Evaluation ◽  
Cure Rates

Abstract BackgroundFecal microbiota transplantation (FMT) has shown high cure rates against recurrent Clostridioides difficile infection regardless of donor microbiota characteristics, whereas the clinical response of FMT in inflammatory bowel disease appears to be donor-dependent. We recently showed that FMT from healthy suckling piglet donors to newborn preterm piglets decreased the risk of necrotizing enterocolitis (NEC), a serious gastrointestinal disease of preterm infants, but could not replicate this finding in a follow-up study using phenotypically similar donors. This gave us the opportunity to directly investigate the microbiota dynamics of clinically efficient FMT. In this experiment, preterm piglets (n=38) were randomly allocated to receive control saline or FMT from inferior (FMT1) or superior donors (FMT2) by rectal administration. All animals were fed infant formula for four days to induce NEC-like lesions before necropsy and gut pathological evaluation. Donor and recipient colonic microbiotas were analyzed by 16S rRNA gene amplicon sequencing and shotgun metagenomics.ResultsAlthough the two donor microbiotas closely resembled one another, only FMT2 recipients had improved body growth and lower intestinal permeability relative to control, and were protected against NEC. Both FMT groups had shifted colon microbiota composition relative to CON, with increased lactobacilli relative abundance, but FMT2 recipients had a higher lactobacilli abundance relative to FMT1. Limosilactobacillus reuteri and Lactobacillus crispatus strains of FMT recipients showed high phylogenetic similarity with their respective donors, indicating successful engraftment. Further, NEC severity was positively associated with Clostridoides difficile, Clostridium perfringens and Enterococcus faecium abundance, while Lmb. reuteri and Lb. crispatus negatively correlated with diarrhea severity. Genome-resolved analysis indicated a higher gut replication rate of lactobacilli in FMT2 recipients, and identified specific glycosaminoglycan-degrading Bacteroides in the superior donor.ConclusionsFMT efficacy against NEC is donor-dependent, and introduced lactobacilli manifest strain-level differences with respect to colonizing recipients. Using shotgun metagenomics, we traced the engrafted strains back from donors and identified donor-specific microbes of potential importance. This may accelerate our understanding of optimal donor selection for clinical FMT.

scholarly journals Fecal filtrate transplantation protects against necrotizing enterocolitis

2021 ◽  
Author(s):  
Anders Brunse ◽  
Ling Deng ◽  
Xiaoyu Pan ◽  
Yan Hui ◽  
Josué L. Castro-Mejía ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Fecal Microbiota Transplantation ◽  
Gastrointestinal Disorder ◽  
Preventive Therapy ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Ileal Mucosa ◽  
Relevant Animal Model ◽  
Life Threatening

AbstractNecrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disorder afflicting preterm infants, which is currently unpreventable. Fecal microbiota transplantation (FMT) is a promising preventive therapy, but the transfer of pathogenic microbes or toxic compounds raise concern. Removal of bacteria from donor feces by micropore filtering may reduce this risk of bacterial infection, while residual bacteriophages could maintain the NEC-preventive effects. We aimed to assess preclinical efficacy and safety of fecal filtrate transplantation (FFT). Using fecal material from healthy suckling piglets, we compared rectal FMT administration (FMT, n = 16) with cognate FFT by either rectal (FFTr, n = 14) or oro-gastric administration (FFTo, n = 13) and saline (CON, n = 16) in preterm, cesarean-delivered piglets as models for preterm infants. We assessed gut pathology and analyzed mucosal and luminal bacterial and viral composition using 16S rRNA gene amplicon and meta-virome sequencing. Finally, we used isolated ileal mucosa, coupled with RNA-Seq, to gauge the host response to the different treatments. Oro-gastric FFT completely prevented NEC, which was confirmed by microscopy, whereas FMT did not perform better than control. Oro-gastric FFT increased viral diversity and reduced Proteobacteria relative abundance in the ileal mucosa relative to control. An induction of mucosal immunity was observed in response to FMT but not FFT. As preterm infants are extremely vulnerable to infections, rational NEC-preventive strategies need incontestable safety profiles. We show in a clinically relevant animal model that FFT, as opposed to FMT, efficiently prevents NEC without any recognizable side effects.

scholarly journals Fecal filtrate transfer protects against necrotizing enterocolitis in preterm pigs

2020 ◽  
Author(s):  
Anders Brunse ◽  
Ling Deng ◽  
Xiaoyu Pan ◽  
Yan Hui ◽  
Witold Kot ◽  
...  
Keyword(s):  
Side Effects ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Defense Mechanisms ◽  
Fecal Microbiota Transplantation ◽  
Gastrointestinal Disorder ◽  
Global Gene Expression ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Ileal Mucosa

ABSTRACTBackground and aimsNecrotizing enterocolitis (NEC) is an acute and life-threatening gastrointestinal disorder afflicting preterm infants, which is currently unpreventable. Fecal microbiota transplantation (FMT) is a promising preventative therapy, but potential side effects raise concern. Removal of bacteria from donor fecal water may reduce side effects while maintaining wanted effects. We aimed to assess preclinical efficacy and safety of bacteria-free fecal filtrate transfer (FFT).MethodsUsing fecal material from healthy suckling piglets, we administered rectal FMT or cognate FFT by either rectal or oro-gastric administration to formula-fed preterm, cesarean piglets, and compared gut pathology and related safety parameters with saline controls. We then analyzed mucosa and luminal bacterial and viral composition using 16S rRNA gene amplicon and metavirome sequencing, respectively. Finally, we used isolated ileal mucosa, coupled with RNA-Seq, to gauge the host response to the different treatments.ResultsOro-gastric FFT eliminated NEC, which was confirmed by microscopy, whereas FMT did not perform better than control. Moreover, FFT but not FMT reduced intestinal permeability, whereas FMT animals had reduced body weight increase and intestinal growth. Oro-gastric FFT increased viral diversity and reduced Proteobacteria abundance in ileal mucosa relative to control. Global gene expression of host mucosa responded to FMT but not FFT with increased and decreased bacterial and viral defense mechanisms, respectively.ConclusionsAs preterm infants are extremely vulnerable, rational therapies need incontestable safety profiles. Here we show in a clinically relevant animal model that FFT, as opposed to FMT, efficiently prevents NEC without any recognizable side effects. If translatable to preterm infants, this could lead to a change of practice and in turn a reduction in NEC burden.

scholarly journals Fecal Microbiota Transplantation: Redefining Surgical Management of Refractory Clostridium difficile Infection

2020 ◽  
Vol 33 (02) ◽  
pp. 092-097 ◽  
Author(s):  
Yao-Wen Cheng ◽  
Monika Fischer
Keyword(s):  
Clostridium Difficile ◽  
Antibiotic Therapy ◽  
Surgical Management ◽  
Salvage Therapy ◽  
Healthy Donor ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Cure Rates

AbstractFecal microbiota transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a diseased individual for therapeutic purposes. It has a clearly defined role in the treatment of recurrent Clostridium difficile (reclassified as “Clostridioides difficile”) infection (CDI), with cure rates over 90% and decreased rates of subsequent recurrence compared with anti-CDI antibiotics. There is emerging evidence that FMT is also effective in the treatment of severe and fulminant CDI, with associated decreases in mortality and colectomy rates compared with standard antibiotic therapy. FMT shows promise as salvage therapy for critically-ill CDI patients refractory to maximum medical therapy and not deemed to be surgical candidates. FMT should be considered early in the course of severe CDI and should be delivered immediately in patients with signs of refractory CDI. Expansion of FMT's use along the spectrum of CDI severity has potential to decrease associated rates of mortality and colectomy.

Fecal microbiota transplantation by enema reduces intestinal injury in experimental necrotizing enterocolitis

2020 ◽  
Vol 55 (6) ◽  
pp. 1094-1098 ◽  
Author(s):  
Jia Liu ◽  
Hiromu Miyake ◽  
Haitao Zhu ◽  
Bo Li ◽  
Mashriq Alganabi ◽  
...  
Keyword(s):  
Necrotizing Enterocolitis ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Intestinal Injury

scholarly journals Lyophilized Fecal Microbiota Transplantation Capsules for Recurrent Clostridium difficile Infection

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S381-S381
Author(s):  
Hebert Dupont ◽  
Zhi-Dong Jiang ◽  
Ashley Alexander ◽  
Nadim Ajami ◽  
Joseph F Petrosino ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Gene Profiling ◽  
Intestinal Microbiome ◽  
Published Data ◽  
Rrna Gene ◽  
Second Phase ◽  
Microbiome Diversity

Abstract Background Fecal microbiota (FM) transplantation (FMT) is a highly effective treatment of recurrent C. difficile infection (rCDI). We have published data showing efficacy of fresh, frozen and lyophilized donor microbiota administered by colonoscopy. Most groups are moving toward use of frozen product given by enema and in evaluating encapsulated product for oral delivery. Methods This was a prospective, randomized study of subjects with rCDI (≥ 3 episodes) treated with encapsulated lyophilized FM 100 g given once or 100 g given on two successive days (total 200 g) vs. frozen FM product 100 g given by single retention enema, between March 2015 and February 2017. The clinical outcome was absence of CDI during the 60 days after FMT. The subjects were followed for 6 months for safety. In a subset recipients, microbiome composition by 16S rRNA gene profiling were analyzed on stools obtained pre- and day 2, 7, 14, 30, 60 and 90 days after FMT. Results A total of 54 subjects were enrolled (37/54; 69% female) with a median age of 71 years (range: 20–97). In the first 14 subjects treated, cure rates for oral capsules 100 g FM was 5/8 (63%) vs. 6/6 (100%) for those receiving 100 g frozen FM by enema (P = 0.209). In the second phase of the study cure rate for oral capsules 200 g FM was 17/18 (91%) vs. 20/21 (94%) for the subjects treated by enema by 100 g of frozen product (P = 0.782). No side effects were felt to be related to the procedure or the FMT products were recorded during 6 months follow-up. Two subjects died during follow-up between 3 and 6 months after study due to underlying medical conditions felt to be unrelated to FMT. Microbiota analysis were performed on 40 subjects of which 19/40 (48%) had received capsules. Figure showed that restoration of the intestinal microbiome diversity and Taxa began apparent by 2 days after FMT in both groups and resembled the donor product by 2 weeks with stabilization of the microbiota diversity and Taxa persisting for the 90 days of observation. Conclusion Administration of encapsulated, lyophilized FM resulted in durable restoration of intestinal microbiome diversity comparable to results seen with frozen product given by enema. Disclosures All authors: No reported disclosures.

scholarly journals Comparative Analysis of Fecal Microbiota Composition Between Rheumatoid Arthritis and Osteoarthritis Patients

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 748 ◽  
Author(s):  
Jin-Young Lee ◽  
Mohamed Mannaa ◽  
Yunkyung Kim ◽  
Jehun Kim ◽  
Geun-Tae Kim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Amplicon Sequencing ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Stool Samples ◽  
Gut Microbiota Composition

The aim of this study was to investigate differences between the gut microbiota composition in patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA). Stool samples from nine RA patients and nine OA patients were collected, and DNA was extracted. The gut microbiome was assessed using 16S rRNA gene amplicon sequencing. The structures and differences in the gut microbiome between RA and OA were analyzed. The analysis of diversity revealed no differences in the complexity of samples. The RA group had a lower Bacteroidetes: Firmicutes ratio than did the OA group. Lactobacilli and Prevotella, particularly Prevotella copri, were more abundant in the RA than in the OA group, although these differences were not statistically significant. The relative abundance of Bacteroides and Bifidobacterium was lower in the RA group. At the species level, the abundance of certain bacterial species was significantly lower in the RA group, such as Fusicatenibacter saccharivorans, Dialister invisus, Clostridium leptum, Ruthenibacterium lactatiformans, Anaerotruncus colihominis, Bacteroides faecichinchillae, Harryflintia acetispora, Bacteroides acidifaciens, and Christensenella minuta. The microbial properties of the gut differed between RA and OA patients, and the RA dysbiosis revealed results similar to those of other autoimmune diseases, suggesting that a specific gut microbiota pattern is related to autoimmunity.

Principles of DNA-Based Gut Microbiota Assessment and Therapeutic Efficacy of Fecal Microbiota Transplantation in Gastrointestinal Diseases

2016 ◽  
Vol 34 (3) ◽  
pp. 279-285 ◽  
Author(s):  
Giovanni Cammarota ◽  
Silvia Pecere ◽  
Gianluca Ianiro ◽  
Luca Masucci ◽  
Diego Currò
Keyword(s):  
Gut Microbiota ◽  
High Throughput Sequencing ◽  
Fecal Microbiota Transplantation ◽  
Gastrointestinal Diseases ◽  
Fecal Microbiota ◽  
Causative Role ◽  
Gastrointestinal Microbiota ◽  
Treatment Protocols ◽  
Irritable Bowel ◽  
Cure Rates

Fecal microbiota transplantation (FMT), a process by which the normal gastrointestinal microbiota is restored, has demonstrated extraordinary cure rates for Clostridium difficile infection and low recurrence. The community of microorganisms within the human gut (or microbiota) is critical to health status and functions; therefore, together with the rise of FMT, the gastrointestinal microbiota has emerged as a ‘virtual' organ with a level of complexity comparable to that of any other organ system and capable to compete with powerful known antibiotics for the treatment of several disorders. Although treatment protocols, donor selection, stool preparation and delivery methods varied widely, with a few reports following an identical protocol, FMT has diffused to other areas where the alterations of the gut microbiota ecology (or dysbiosis) have been theorized to play a causative role, including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), among several other extra-intestinal disorders (i.e. metabolic syndrome and obesity, multiple sclerosis, cardiovascular diseases). FMT can be relatively simple to perform, but a number of challenges need to be overcome before this procedure is widely accepted in clinical practice, and currently, there is no consensus between the various gastrointestinal organizations and societies regarding the FMT procedure. In this article, we describe the modern high-throughput sequencing techniques to characterize the composition of gut microbiota and the potential for therapeutics by manipulating microbiota with FMT in several gastrointestinal disorders (C. difficile-associated diarrhea, IBD and IBS), with a look on the potential future directions of FMT.

scholarly journals Intrinsic challenges in ancient microbiome reconstruction using 16S rRNA gene amplification

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Kirsten A. Ziesemer ◽  
Allison E. Mann ◽  
Krithivasan Sankaranarayanan ◽  
Hannes Schroeder ◽  
Andrew T. Ozga ◽  
...  
Keyword(s):  
16S Rrna ◽  
16S Rrna Gene ◽  
Dna Amplification ◽  
Amplicon Sequencing ◽  
Universal Primers ◽  
Rrna Gene ◽  
Dental Calculus ◽  
Shotgun Metagenomics ◽  
Variable Regions ◽  
V3 Region

Abstract To date, characterization of ancient oral (dental calculus) and gut (coprolite) microbiota has been primarily accomplished through a metataxonomic approach involving targeted amplification of one or more variable regions in the 16S rRNA gene. Specifically, the V3 region (E. coli 341–534) of this gene has been suggested as an excellent candidate for ancient DNA amplification and microbial community reconstruction. However, in practice this metataxonomic approach often produces highly skewed taxonomic frequency data. In this study, we use non-targeted (shotgun metagenomics) sequencing methods to better understand skewed microbial profiles observed in four ancient dental calculus specimens previously analyzed by amplicon sequencing. Through comparisons of microbial taxonomic counts from paired amplicon (V3 U341F/534R) and shotgun sequencing datasets, we demonstrate that extensive length polymorphisms in the V3 region are a consistent and major cause of differential amplification leading to taxonomic bias in ancient microbiome reconstructions based on amplicon sequencing. We conclude that systematic amplification bias confounds attempts to accurately reconstruct microbiome taxonomic profiles from 16S rRNA V3 amplicon data generated using universal primers. Because in silico analysis indicates that alternative 16S rRNA hypervariable regions will present similar challenges, we advocate for the use of a shotgun metagenomics approach in ancient microbiome reconstructions.

scholarly journals Higher fiber complementary food alters Fecal microbiota composition and normalizes stool form in Malawian children: A randomized trial

2021 ◽  
Vol 21 (04) ◽  
pp. 17854-17875
Author(s):  
Edda Lungu ◽  
◽  
J Auger ◽  
A Piano ◽  
WJ Dahl ◽  
...  
Keyword(s):  
Dietary Intake ◽  
Bacterial Species ◽  
Amplicon Sequencing ◽  
Fecal Microbiota ◽  
Stool Frequency ◽  
Sub Saharan Africa ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Linear Discriminant ◽  
Stool Form

Dietary fiber favorably modulates gut microbiota and may be protective against diarrhea in sub-Saharan Africa where rates in infants and young children are high. Soybean hull is high in fiber and accessible in rural Africa; however, its use in complementary feeding has not been evaluated. The objective of this study was to determine the acceptability and feasibility of a soybean, soy hull fiber, and maize (SFM) blend food; the primary outcome was compliance to the feeding protocol. Secondary outcomes were stool form and frequency, fecal microbiota composition, growth and dietary intake. In a parallel, single-blind study, children 6-36 months of age from the Lilongwe district of Malawi were randomized to receive daily SFM (n=69) or maize only(n=10) porridge(phala) for 6 months. Anthropometrics were measured monthly, and compliance, stool frequency,and stool form, weekly. At baseline, 3-month,and 6-month (study end) time points, dietary intake (24-h recall) was assessed,and fecal samples were collected. Fecal DNA was analyzed by Real-Time polymerase chain reaction (PCR) for microbes of interest and 16S rRNA gene amplicon sequencing. Mothers accessed the acceptability and feasibility of the study foods at study end. Mothers reported excellent compliance to feeding the SFM porridge, rated it more acceptable than maize,and noted improved appetite, weight, and stool consistency of their children. Stool frequency at baseline (2±1 stools/d) was unchanged with intervention; however, there were significantly fewer diarrhea-type stools reported during study months 4-6 vs.1-3 for the SFM group, whereas no improvement was seen for the maize group. At study end, the fecal abundance ofAkkermansia muciniphila was enriched in children receiving the SFM, compared to maize (p<0.05), and a trend for increased Faecalibacterium prausnitzii (p=0.07) was seen. A comparison of fecal microbiota composition using linear discriminant analysis effect size (LEfSe)showed notable differences in numerous taxa in the SFM group compared to baseline, whereas the maize comparator exhibited fewer changes. Fiber intake was higher for the SFMgroup, compared to maize at 6 months (13.7±3.8 vs. 8.4±4.5 g/day, p<0.01). Weight-for-height and BMI-for-age Z-scores were significantly higher for the SFM group. In young Malawian children, feeding a blend of soybean, soy hulls and maize reduced diarrhea-type stools and increased the abundance of Akkermansia muciniphila, a bacterial species involved in maintaining intestinal health, and thus may provide a feasible means of improving wellness in children in resource-poor settings through the modulation of microbiota composition.

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