Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity

DeFilipp, Zachariah; Peled, Jonathan U.; Li, Shuli; Mahabamunuge, Jasmin; Dagher, Zeina; Slingerland, Ann E.; Rio, Candice Del; Valles, Betsy; Kempner, Maria E.; Smith, Melissa; Brown, Jami; Dey, Bimalangshu R.; El‐Jawahri, Areej; McAfee, Steven L.; Spitzer, Thomas R.; Ballen, Karen K.; Sung, Anthony D.; Dalton, Tara; Messina, Julia A.; Dettmer, Katja; Liebisch, Gerhard; Oefner, Peter J.; Taur, Ying; Pamer, Eric G.; Holler, Ernst; Mansour, Michael K.; Brink, Marcel R.M. van den; Hohmann, Elizabeth L.; Jenq, Robert R.; Chen, Yi-Bin

doi:10.1182/bloodadvances.2018017731

Cited by 178 publications

(155 citation statements)

References 36 publications

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“…Two cases of adult intestinal toxemia botulism in allogeneic hematopoietic cell transplant recipients have been reported [45,47]. Alteration of the intestinal flora may occur as a result of antibiotics before and during hematopoietic cell transplant, administration of chemotherapy and/or radiation, and altered nutritional patterns [50]. One case has been recorded where the immunosuppressant cyclosporine was administered in the 53 days prior to symptom onset [47].…”

Section: Predisposing Factorsmentioning

confidence: 99%

Adult Intestinal Toxemia Botulism

Harris

Anniballi

Austin

2020

Toxins

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Intoxication with botulinum neurotoxin can occur through various routes. Foodborne botulism results after consumption of food in which botulinum neurotoxin-producing clostridia (i.e., Clostridium botulinum or strains of Clostridium butyricum type E or Clostridium baratii type F) have replicated and produced botulinum neurotoxin. Infection of a wound with C. botulinum and in situ production of botulinum neurotoxin leads to wound botulism. Colonization of the intestine by neurotoxigenic clostridia, with consequent production of botulinum toxin in the intestine, leads to intestinal toxemia botulism. When this occurs in an infant, it is referred to as infant botulism, whereas in adults or children over 1 year of age, it is intestinal colonization botulism. Predisposing factors for intestinal colonization in children or adults include previous bowel or gastric surgery, anatomical bowel abnormalities, Crohn's disease, inflammatory bowel disease, antimicrobial therapy, or foodborne botulism. Intestinal colonization botulism is confirmed by detection of botulinum toxin in serum and/or stool, or isolation of neurotoxigenic clostridia from the stool, without finding a toxic food. Shedding of neurotoxigenic clostridia in the stool may occur for a period of several weeks. Adult intestinal botulism occurs as isolated cases, and may go undiagnosed, contributing to the low reported incidence of this rare disease.

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Section: Predisposing Factorsmentioning

confidence: 99%

Adult Intestinal Toxemia Botulism

Harris

Anniballi

Austin

2020

Toxins

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“…(p5) The specific make‐up of the gut microbiota is influenced by numerous factors, including host genotype, age, diet, localized inflammation, antimicrobial use, and direct invasion of pathogenic organisms . In animals and humans, alterations in the gut microbiota have been linked to several important diseases and conditions, including obesity, Crohn's disease, diabetes mellitus, ulcerative colitis, and some forms of neoplasia, making it an important area of current research …”

Section: Introduction: the Gut Microbiota In Health And Diseasementioning

confidence: 99%

The role of the gut microbiota on animal model reproducibility

Turner

2018

Anim Models and Exp Med

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The gut microbiota is composed of approximately 10 10 ‐10 14 cells, including fungi, bacteria, archaea, protozoa, viruses, and bacteriophages; their genes and their various metabolites were found throughout the gastrointestinal tract. It has co‐evolved with each species to assist with day to day bodily functions, such as digestion, metabolism of xenobiotics, development of mucosal immunity and immunomodulation, and protection against invading pathogens. Because of the significant beneficial impact that gut microbiota may have, there is interest in learning more about it and translating these findings into clinical therapies. Results from recent studies characterizing the gut microbiota of various species have demonstrated the range of influences that may affect gut microbiota diversity, including animal strain, obesity, types of enrichment used, bedding and housing methods, treatment with antimicrobials, vendor source, specific animal housing, diet, and intercurrent disease. Relatively little is known about the functional consequences of alterations of the gut microbiota and exactly how changes in richness and diversity of the microbiota translate into changes in health and susceptibility to disease. Furthermore, questions have been raised as to whether germ‐free or even ultraclean, barrier‐raised mice are relevant models of human disease, given their significantly reduced gut microbiota diversity and complexity compared with conventionally housed mice. In addition, evidence suggests that the specific anatomical location selected for assessing the gut microbiota has a highly significant effect on study outcomes, in that bacterial phyla change significantly along the gastrointestinal tract. This paper will explore animal model reproducibility in light of this information about the gut microbiota.

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“…This increase in O 2 may provide a potential mechanistic explanation for changes in microbiome associated with GVHD and IBD. The change in O 2 levels might lead to dysbiosis with loss of microbial diversity, decrease in commensals such as obligate anaerobes and shift towards to aerobes and pathobionts in the microbiome of patients with GVHD and IBD 43 44 45 46 47 48 49 50 51 52 53 54 55 .…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Complex II In Intestinal Epithelial Cells Regulates T-cell Mediated Immunopathology

Fujiwara

Mathew

Kovalenko

et al. 2020

Preprint

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Keywords: mitochondria, succinate dehydrogenase, bone marrow transplantation, graft-versus-host 22 disease, intestinal epithelium 23 24 25Summary 26Intestinal epithelial cell (IEC) damage by T cells contributes to alloimmune, autoimmune and iatrogenic 27 diseases such as graft-versus-host disease (GVHD), inflammatory bowel disease (IBD) and immune 28 checkpoint blockade (ICB) mediated colitis, respectively. Despite significant advances in understanding 29 the aberrant biology of T cells in these diseases, little is known about how the fundamental biological 30 processes of the target IECs influence the disease severity. Here, through analyses of metabolic 31 pathways of IECs, we identified disruption of oxidative phosphorylation without a concomitant change 32 in glycolysis and an increase in succinate levels in several distinct in vivo models of T cell mediated 33 mediated gastrointestinal graft-versus-host disease (GI-GVHD) often have similar symptoms and cause 50 significant morbidity and mortality 1 5 6 . Although the pathophysiology of each of these diseases is a 51 complex interplay of the environmental and genetic factors, T cell mediated damage of IECs plays a 52 vital role in the cause and severity of all of these conditions. Immunosuppression with corticosteroids, 53 and anti-cytokine therapies have shown good results with adverse effects, but are still incomplete 5 7 8 . 54The biology and treatments of these diseases are often understood and targeted from the immune cell 55 3 and inflammation perspective, but the pathogenesis and severity from host IEC target cell perspective 56 remain undefined. 57 58 Emerging data in recent years have brought into focus the central role of immune cell metabolism in the 59 regulation of intestinal inflammatory diseases. APCs, including macrophages and dendritic cells, and T 60 cells show changes in metabolic programming, including morphological alterations in mitochondria, 61transitioning from glycolysis dependence (pro-inflammatory macrophages and effector T cells) to 62 oxidative phosphorylation (OXPHOS) dependence (anti-inflammatory macrophages and memory T 63 cells) 9 10 11 and regulate intestinal T cell mediated diseases such as GI GVHD and IBD. However, 64whether the metabolism of the targets of these pathogenic T cells in these diseases, the IECs, are 65 perturbed or reprogrammed, and if so, whether this has an impact on the disease severity remains 66 unknown. The mammalian GI tract is a relatively hypoxic region and thus, IECs are uniquely adapted to 67 this hypoxic environment 12 13 . In this study, we aimed to determine the metabolic changes in IECs when 68 they are targeted by pathogenic T effector cells. We found that in the context of pathogenic T cell 69 mediated damage, the IECs demonstrated a reduction in OXPHOS and accumulated succinate as a result 70 of decrease in SDHA, a component of mitochondrial complex II. The reduction of SDHA in IECs 71 aggravated disease severity in multiple T cell mediated models such as the alloimmune mediated GI 72 GVHD, ...

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Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity

Cited by 178 publications

References 36 publications

Adult Intestinal Toxemia Botulism

Adult Intestinal Toxemia Botulism

The role of the gut microbiota on animal model reproducibility

Mitochondrial Complex II In Intestinal Epithelial Cells Regulates T-cell Mediated Immunopathology

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