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 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 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 16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis

2009 ◽  
Vol 3 (8) ◽  
pp. 944-954 ◽  
Author(s):  
Yunwei Wang ◽  
Jeanette D Hoenig ◽  
Kathryn J Malin ◽  
Sanaa Qamar ◽  
Elaine O Petrof ◽  
...  
Keyword(s):  
16S Rrna ◽  
16S Rrna Gene ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Fecal Microbiota ◽  
Rrna Gene

scholarly journals Necrotizing enterocolitis and the microbiome: Current status and future directions

2020 ◽  
Author(s):  
Robert Thänert ◽  
Eric C Keen ◽  
Gautam Dantas ◽  
Barbara B Warner ◽  
Phillip I Tarr
Keyword(s):  
Risk Factors ◽  
Preterm Infant ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Clinical Characteristics ◽  
Gastrointestinal Disorder ◽  
Current Status ◽  
Future Directions ◽  
Barrier Integrity ◽  
Microbial Dysbiosis

Abstract Decades of research have failed to define the pathophysiology of necrotizing enterocolitis (NEC), a devastating pediatric gastrointestinal disorder of preterm infants. However, recent evidence suggests that host-microbiota interactions, in which microbial dysbiosis is followed by loss of barrier integrity, inflammation, and necrosis, are central to NEC development. Thus, greater knowledge of the preterm infant microbiome could accelerate attempts to diagnose, treat, and prevent NEC. Here, we summarize clinical characteristics of and risk factors for NEC, the structure of the pre-event NEC microbiome, how this community interfaces with host immunology, and microbiome-based approaches that might prevent or lessen the severity of NEC in this very vulnerable population.

scholarly journals Influence of Family Integrated Care on the Intestinal Microbiome of Preterm Infants With Necrotizing Enterocolitis and Enterostomy: A Preliminary Study

2021 ◽  
Vol 9 ◽  
Author(s):  
Mengyang Yang ◽  
Juan Du ◽  
Qin Yang ◽  
Wenyan Dou ◽  
Min Jiang ◽  
...  
Keyword(s):  
Integrated Care ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Premature Infants ◽  
Intestinal Flora ◽  
Intestinal Microbiome ◽  
Rrna Gene ◽  
Α Diversity ◽  
Family Integrated Care ◽  
Family Integrated

The aim of this study was to investigate the influence of family integrated care (FICare) on the intestinal microbiome of preterm infants with necrotizing enterocolitis and enterostomy. This was a prospective pilot study at Beijing Children's Hospital. Premature infants with an enterostomy who met the enrollment criteria were divided into the 2-week FICare and non-FICare groups (non-randomly). We collected their fecal samples and subjected the intestinal microbiomes to 16S rRNA gene sequencing. Operational taxonomic units (OTU) were analyzed to assess the intestinal microbiome richness, and we then carried out α-diversity, β-diversity, and species clustering analyses and a linear discriminant analysis (LDA) effect size (LEfSe) analysis to identify the differences in the microbial communities between the two groups. There were 12 patients enrolled in the study (FICare, n = 7; non-FICare, n = 5). There were no significant between-group differences in demographic characteristics, or in the relative abundances of phyla and genera. The major bacterial phyla were Proteobacteria, Firmicutes, and Actinobacteria, and Serratia, Enterococcus, Cronobacter, and Bifidobacterium dominated at the genus level. The α-diversity analysis indicated that the intestinal flora was more diverse in the non-FICare group than the FICare group (p < 0.05). However, most of the other indicators did not suggest a difference between the two groups. There was a high proportion of shared OTUs between the two groups, and the PCoA and clustering analyses indicated that the two groups were difficult to distinguish, indicating that the intestinal microbiomes were relatively similar between the groups. In summary, short-term FICare had no significant positive effect on the establishment of intestinal flora diversity in premature infants with necrotizing enterocolitis and enterostomy. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-OPN-17011801).

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 Intestinal Microbiota: A Novel Target to Improve Anti-Tumor Treatment?

2019 ◽  
Vol 20 (18) ◽  
pp. 4584 ◽  
Author(s):  
Romain Villéger ◽  
Amélie Lopès ◽  
Guillaume Carrier ◽  
Julie Veziant ◽  
Elisabeth Billard ◽  
...  
Keyword(s):  
Side Effects ◽  
Gut Microbiota ◽  
Host Response ◽  
Fecal Microbiota Transplantation ◽  
Direct Interaction ◽  
Fecal Microbiota ◽  
Intestinal Microbiome ◽  
Wide Range ◽  
Novel Target

Recently, preclinical and clinical studies targeting several types of cancer strongly supported the key role of the gut microbiota in the modulation of host response to anti-tumoral therapies such as chemotherapy, immunotherapy, radiotherapy and even surgery. Intestinal microbiome has been shown to participate in the resistance to a wide range of anticancer treatments by direct interaction with the treatment or by indirectly stimulating host response through immunomodulation. Interestingly, these effects were described on colorectal cancer but also in other types of malignancies. In addition to their role in therapy efficacy, gut microbiota could also impact side effects induced by anticancer treatments. In the first part of this review, we summarized the role of the gut microbiome on the efficacy and side effects of various anticancer treatments and underlying mechanisms. In the second part, we described the new microbiota-targeting strategies, such as probiotics and prebiotics, antibiotics, fecal microbiota transplantation and physical activity, which could be effective adjuvant therapies developed in order to improve anticancer therapeutic efficiency.

scholarly journals Gut microbiota determines the social behavior of mice and induces metabolic and inflammatory changes in their adipose tissue

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Oryan Agranyoni ◽  
Sapir Meninger-Mordechay ◽  
Atara Uzan ◽  
Oren Ziv ◽  
Mali Salmon-Divon ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Social Behavior ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Critical Role ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
The Social ◽  
Inflammatory Profile

AbstractThe link between the gut microbiota and social behavior has been demonstrated, however the translational impact of a certain microbiota composition on stable behavioral patterns is yet to be elucidated. Here we employed an established social behavior mouse model of dominance (Dom) or submissiveness (Sub). A comprehensive 16S rRNA gene sequence analysis of Dom and Sub mice revealed a significantly different gut microbiota composition that clearly distinguishes between the two behavioral modes. Sub mice gut microbiota is significantly less diverse than that of Dom mice, and their taxa composition uniquely comprised the genera Mycoplasma and Anaeroplasma of the Tenericutes phylum, in addition to the Rikenellaceae and Clostridiaceae families. Conversely, the gut microbiota of Dom mice includes the genus Prevotella of the Bacteriodetes phylum, significantly less abundant in Sub mice. In addition, Sub mice show lower body weight from the age of 2 weeks and throughout their life span, accompanied with lower epididymis white adipose tissue (eWAT) mass and smaller adipocytes together with substantially elevated expression of inflammation and metabolic-related eWAT adipokines. Finally, fecal microbiota transplantation into germ-free mice show that Sub-transplanted mice acquired Sub microbiota and adopted their behavioral and physiological features, including depressive-like and anti-social behaviors alongside reduced eWAT mass, smaller adipocytes, and a Sub-like eWAT adipokine profile. Our findings demonstrate the critical role of the gut microbiome in determining dominance vs. submissiveness and suggest an association between gut microbiota, the eWAT metabolic and inflammatory profile, and the social behavior mode.

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