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REVIEW
Zhenrun J Zhang, Christopher J Lehmann, Cody G Cole, Eric G Pamer
Extensive research has elucidated the influence of the gut microbiota on human health and disease susceptibility and resistance. We review recent clinical and laboratory-based experimental studies associating the gut microbiota with certain human diseases. We also highlight ongoing translational advances that manipulate the gut microbiota to treat human diseases and discuss opportunities and challenges in translating microbiome research from and to the bedside. Expected final online publication date for the Annual Review of Microbiology , Volume 76 is September 2022...
June 2, 2022: Annual Review of Microbiology
#22
JOURNAL ARTICLE
Jinyuan Yan, Chen Liao, Bradford P Taylor, Emily Fontana, Luigi A Amoretti, Roberta J Wright, Eric R Littmann, Anqi Dai, Nicholas Waters, Jonathan U Peled, Ying Taur, Miguel-Angel Perales, Benjamin A Siranosian, Ami S Bhatt, Marcel R M van den Brink, Eric G Pamer, Jonas Schluter, Joao B Xavier
Hospitalized patients receiving hematopoietic cell transplants provide a unique opportunity to study the human gut microbiome. We previously compiled a large-scale longitudinal dataset of fecal microbiota and associated metadata, but we had limited that analysis to taxonomic composition of bacteria from 16S rRNA gene sequencing. Here we augment those data with shotgun metagenomics. The compilation amounts to a nested subset of 395 samples compiled from different studies at Memorial Sloan Kettering. Shotgun metagenomics describes the microbiome at the functional level, particularly in antimicrobial resistances and virulence factors...
May 18, 2022: Scientific Data
#23
REVIEW
Matthew T Sorbara, Eric G Pamer
Symbiotic microorganisms inhabiting the gastrointestinal tract promote health by decreasing susceptibility to infection and enhancing resistance to a range of diseases. In this Review, we discuss our increasing understanding of the impact of the microbiome on the mammalian host and recent efforts to culture and characterize intestinal symbiotic microorganisms that produce or modify metabolites that impact disease pathology. Manipulation of the intestinal microbiome has great potential to reduce the incidence and/or severity of a wide range of human conditions and diseases, and the biomedical research community now faces the challenge of translating our understanding of the microbiome into beneficial medical therapies...
June 2022: Nature Reviews. Microbiology
#24
JOURNAL ARTICLE
Sejal Morjaria, Allen W Zhang, Sohn Kim, Jonathan U Peled, Simone Becattini, Eric R Littmann, Eric G Pamer, Michael C Abt, Miguel-Angel Perales
Background: Monocytes are an essential cellular component of the innate immune system that support the host's effectiveness to combat a range of infectious pathogens. Hemopoietic cell transplantation (HCT) results in transient monocyte depletion, but the factors that regulate recovery of monocyte populations are not fully understood. In this study, we investigated whether the composition of the gastrointestinal microbiota is associated with the recovery of monocyte homeostasis after HCT...
December 2020: Clinical hematology international
#25
JOURNAL ARTICLE
Arianna Miles-Jay, Vincent B Young, Eric G Pamer, Tor C Savidge, Mini Kamboj, Kevin W Garey, Evan S Snitkin
Clostridioides difficile is the leading cause of healthcare-associated infectious diarrhoea. However, it is increasingly appreciated that healthcare-associated infections derive from both community and healthcare environments, and that the primary sites of C. difficile transmission may be strain-dependent. We conducted a multisite genomic epidemiology study to assess differential genomic evidence of healthcare vs community spread for two of the most common C. difficile strains in the USA: sequence type (ST) 1 (associated with ribotype 027) and ST2 (associated with ribotype 014/020)...
June 2021: Microbial Genomics
#26
Chen Liao, Bradford P Taylor, Camilla Ceccarani, Emily Fontana, Luigi A Amoretti, Roberta J Wright, Antonio L C Gomes, Jonathan U Peled, Ying Taur, Miguel-Angel Perales, Marcel R M van den Brink, Eric Littmann, Eric G Pamer, Jonas Schluter, Joao B Xavier
No abstract text is available yet for this article.
April 23, 2021: Scientific Data
#27
JOURNAL ARTICLE
Chen Liao, Bradford P Taylor, Camilla Ceccarani, Emily Fontana, Luigi A Amoretti, Roberta J Wright, Antonio L C Gomes, Jonathan U Peled, Ying Taur, Miguel-Angel Perales, Marcel R M van den Brink, Eric Littmann, Eric G Pamer, Jonas Schluter, Joao B Xavier
The impact of the gut microbiota in human health is affected by several factors including its composition, drug administrations, therapeutic interventions and underlying diseases. Unfortunately, many human microbiota datasets available publicly were collected to study the impact of single variables, and typically consist of outpatients in cross-sectional studies, have small sample numbers and/or lack metadata to account for confounders. These limitations can complicate reusing the data for questions outside their original focus...
March 2, 2021: Scientific Data
#28
JOURNAL ARTICLE
Hea-Jin Jung, Matthew T Sorbara, Eric G Pamer
Gram-negative pathogens, such as Klebsiella pneumoniae, remodel their outer membrane (OM) in response to stress to maintain its integrity as an effective barrier and thus to promote their survival in the host. The emergence of carbapenem-resistant K. pneumoniae (CR-Kp) strains that are resistant to virtually all antibiotics is an increasing clinical problem and OM impermeability has limited development of antimicrobial agents because higher molecular weight antibiotics cannot access sites of activity. Here, we demonstrate that TAM (translocation and assembly module) deletion increases CR-Kp OM permeability under stress conditions and enhances sensitivity to high-molecular weight antimicrobials...
February 8, 2021: PLoS Pathogens
#29
JOURNAL ARTICLE
Simone Becattini, Matthew T Sorbara, Sohn G Kim, Eric L Littmann, Qiwen Dong, Gavin Walsh, Roberta Wright, Luigi Amoretti, Emily Fontana, Tobias M Hohl, Eric G Pamer
The gut microbiota produces metabolites that regulate host immunity, thereby impacting disease resistance and susceptibility. The extent to which commensal bacteria reciprocally respond to immune activation, however, remains largely unexplored. Herein, we colonized mice with four anaerobic symbionts and show that acute immune responses result in dramatic transcriptional reprogramming of these commensals with minimal changes in their relative abundance. Transcriptomic changes include induction of stress-response mediators and downregulation of carbohydrate-degrading factors such as polysaccharide utilization loci (PULs)...
February 2, 2021: Cell Host & Microbe
#30
MULTICENTER STUDY
Niloufer Khan, Sarah Lindner, Antonio L C Gomes, Sean M Devlin, Gunjan L Shah, Anthony D Sung, Craig S Sauter, Heather J Landau, Parastoo B Dahi, Miguel-Angel Perales, David J Chung, Alexander M Lesokhin, Anqi Dai, Annelie Clurman, John B Slingerland, Ann E Slingerland, Daniel G Brereton, Paul A Giardina, Molly Maloy, Gabriel K Armijo, Carlos Rondon-Clavo, Emily Fontana, Lauren Bohannon, Sendhilnathan Ramalingam, Amy T Bush, Meagan V Lew, Julia A Messina, Eric Littmann, Ying Taur, Robert R Jenq, Nelson J Chao, Sergio Giralt, Kate A Markey, Eric G Pamer, Marcel R M van den Brink, Jonathan U Peled
We previously described clinically relevant reductions in fecal microbiota diversity in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Recipients of high-dose chemotherapy and autologous HCT (auto-HCT) incur similar antibiotic exposures and nutritional alterations. To characterize the fecal microbiota in the auto-HCT population, we analyzed 1161 fecal samples collected from 534 adult recipients of auto-HCT for lymphoma, myeloma, and amyloidosis in an observational study conducted at 2 transplantation centers in the United States...
March 18, 2021: Blood
#31
JOURNAL ARTICLE
Brooke W Bullington, Myung Hee Lee, Jane Mlingi, Ndalloh Paul, Christine Aristide, Emily Fontana, Eric R Littmann, Crispin Mukerebe, Peter Shigella, Philibert Kashangaki, Samuel E Kalluvya, Claudia J de Dood, Govert J van Dam, Paul L A M Corstjens, Daniel W Fitzgerald, Eric G Pamer, Jennifer A Downs
Schistosome infection is recognized as a potentially modifiable risk factor for HIV in women by the World Health Organization. Alterations in cervicovaginal bacteria have been associated with HIV acquisition and have not been studied in schistosome infection. We collected cervical swabs from Tanzanian women with and without S. mansoni and S. haematobium to determine effects on cervicovaginal microbiota. Infected women were treated, and follow-up swabs were collected after 3 months. 16S rRNA sequencing was performed on DNA extracted from swabs...
May 2021: ISME Journal
#32
JOURNAL ARTICLE
Simone Becattini, Eric R Littmann, Ruth Seok, Luigi Amoretti, Emily Fontana, Roberta Wright, Mergim Gjonbalaj, Ingrid M Leiner, George Plitas, Tobias M Hohl, Eric G Pamer
Tissue resident memory CD8+ T cells (Trm) are poised for immediate reactivation at sites of pathogen entry and provide optimal protection of mucosal surfaces. The intestinal tract represents a portal of entry for many infectious agents; however, to date specific strategies to enhance Trm responses at this site are lacking. Here, we present TMDI (Transient Microbiota Depletion-boosted Immunization), an approach that leverages antibiotic treatment to temporarily restrain microbiota-mediated colonization resistance, and favor intestinal expansion to high densities of an orally-delivered Listeria monocytogenes strain carrying an antigen of choice...
September 8, 2020: Nature Communications
#33
JOURNAL ARTICLE
Matthew T Sorbara, Eric R Littmann, Emily Fontana, Thomas U Moody, Claire E Kohout, Mergim Gjonbalaj, Vincent Eaton, Ruth Seok, Ingrid M Leiner, Eric G Pamer
Bacteria belonging to the Lachnospiraceae family are abundant, obligate anaerobic members of the microbiota in healthy humans. Lachnospiraceae impact their hosts by producing short-chain fatty acids, converting primary to secondary bile acids, and facilitating colonization resistance against intestinal pathogens. To increase our understanding of genomic and functional diversity between members of this family, we cultured 273 Lachnospiraceae isolates representing 11 genera and 27 species from human donors and performed whole-genome sequencing assembly and annotation...
July 8, 2020: Cell Host & Microbe
#34
MULTICENTER STUDY
Kate A Markey, Jonas Schluter, Antonio L C Gomes, Eric R Littmann, Amanda J Pickard, Bradford P Taylor, Paul A Giardina, Daniela Weber, Anqi Dai, Melissa D Docampo, Gabriel K Armijo, Ann E Slingerland, John B Slingerland, Katherine B Nichols, Daniel G Brereton, Annelie G Clurman, Ruben J Ramos, Arka Rao, Amy Bush, Lauren Bohannon, Megan Covington, Meagan V Lew, David A Rizzieri, Nelson Chao, Molly Maloy, Christina Cho, Ioannis Politikos, Sergio Giralt, Ying Taur, Eric G Pamer, Ernst Holler, Miguel-Angel Perales, Doris M Ponce, Sean M Devlin, Joao Xavier, Anthony D Sung, Jonathan U Peled, Justin R Cross, Marcel R M van den Brink
Studies of the relationship between the gastrointestinal microbiota and outcomes in allogeneic hematopoietic stem cell transplantation (allo-HCT) have thus far largely focused on early complications, predominantly infection and acute graft-versus-host disease (GVHD). We examined the potential relationship of the microbiome with chronic GVHD (cGVHD) by analyzing stool and plasma samples collected late after allo-HCT using a case-control study design. We found lower circulating concentrations of the microbe-derived short-chain fatty acids (SCFAs) propionate and butyrate in day 100 plasma samples from patients who developed cGVHD, compared with those who remained free of this complication, in the initial case-control cohort of transplant patients and in a further cross-sectional cohort from an independent transplant center...
July 2, 2020: Blood
#35
JOURNAL ARTICLE
Kathleen G L Ma, Kvin Lertpiriyapong, Alessandra Piersigilli, Irina Dobtsis, Juliette R K Wipf, Eric R Littmann, Ingrid Leiner, Eric G Pamer, Rodolfo J Ricart Arbona, Neil S Lipman
Clostridioides difficile is an enteric pathogen that can cause significant clinical disease in both humans and animals. However, clinical disease arises most commonly after treatment with broad-spectrum antibiotics. The organism's ability to cause naturally occurring disease in mice is rare, and little is known about its clinical significance in highly immunocompromised mice. We report on 2 outbreaks of diarrhea associated with C. difficile in mice. In outbreak 1, 182 of approximately 2, 400 NOD.Cg- Prkdcscid Il2rgtm1Wjl /SzJ (NSG) and related strains of mice became clinically ill after cessation of a 14-d course of 0...
June 1, 2020: Comparative Medicine
#36
MULTICENTER STUDY
Jonathan U Peled, Antonio L C Gomes, Sean M Devlin, Eric R Littmann, Ying Taur, Anthony D Sung, Daniela Weber, Daigo Hashimoto, Ann E Slingerland, John B Slingerland, Molly Maloy, Annelie G Clurman, Christoph K Stein-Thoeringer, Kate A Markey, Melissa D Docampo, Marina Burgos da Silva, Niloufer Khan, André Gessner, Julia A Messina, Kristi Romero, Meagan V Lew, Amy Bush, Lauren Bohannon, Daniel G Brereton, Emily Fontana, Luigi A Amoretti, Roberta J Wright, Gabriel K Armijo, Yusuke Shono, Míriam Sanchez-Escamilla, Nerea Castillo Flores, Ana Alarcon Tomas, Richard J Lin, Lucrecia Yáñez San Segundo, Gunjan L Shah, Christina Cho, Michael Scordo, Ioannis Politikos, Kasumi Hayasaka, Yuta Hasegawa, Boglarka Gyurkocza, Doris M Ponce, Juliet N Barker, Miguel-Angel Perales, Sergio A Giralt, Robert R Jenq, Takanori Teshima, Nelson J Chao, Ernst Holler, Joao B Xavier, Eric G Pamer, Marcel R M van den Brink
BACKGROUND: Relationships between microbiota composition and clinical outcomes after allogeneic hematopoietic-cell transplantation have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable. METHODS: The microbiota composition of fecal samples obtained from patients who were undergoing allogeneic hematopoietic-cell transplantation at four centers was profiled by means of 16S ribosomal RNA gene sequencing...
February 27, 2020: New England Journal of Medicine
#37
JOURNAL ARTICLE
Igor Stoma, Eric R Littmann, Jonathan U Peled, Sergio Giralt, Marcel R M van den Brink, Eric G Pamer, Ying Taur
BACKGROUND: Gram-negative bloodstream infections represent a significant complication facing allogeneic hematopoietic cell transplant (allo-HCT) recipients, as a result of intestinal translocation during neutropenia. In this study we sought to better understand how the composition of the intestinal microbiota is connected to risk of gram-negative bloodstream infections, expanding on our prior work in these patients. METHODS: Fecal specimens were collected from recipients of allo-HCT and analyzed using 16SrRNA gene sequencing...
January 24, 2020: Clinical Infectious Diseases
#38
JOURNAL ARTICLE
Mergim Gjonbalaj, James W Keith, Mytrang H Do, Tobias M Hohl, Eric G Pamer, Simone Becattini
The complex bacterial populations that constitute the gut microbiota can harbor antibiotic-resistance genes (ARGs), including those encoding for β-lactamase enzymes (BLA), which degrade commonly prescribed antibiotics such as ampicillin. Prevalence of such genes in commensal bacteria has been increased in recent years by the wide use of antibiotics in human populations and in livestock. While transfer of ARGs between bacterial species has well-established dramatic public health implications, these genes can also function in trans within bacterial consortia, where antibiotic-resistant bacteria can provide antibiotic-sensitive neighbors with leaky protection from drugs, as shown both in vitro and in vivo, in models of lung and subcutaneous co-infection...
January 21, 2020: Infection and Immunity
#39
JOURNAL ARTICLE
James Keith, Qiwen Dong, Matthew T Sorbara, Simone Becattini, Jonathan K Sia, Mergim Gjonbalaj, Ruth Seok, Ingrid Leiner, Eric Littmann, Eric G Pamer
Antibiotic treatment of patients undergoing complex medical treatments can deplete commensal bacterial strains from the intestinal microbiota, thereby reducing colonization resistance against a wide range of antibiotic-resistant pathogens. Loss of colonization resistance can lead to marked expansion of Vancomycin-resistant Enterococcus faecium (VRE), Klebsiella pneumoniae (Kp) and Escherichia coli (Ec) in the intestinal lumen, predisposing patients to bloodstream invasion and sepsis. The impact of intestinal domination by these antibiotic-resistant pathogens on mucosal immune defenses and epithelial and mucin-mediated barrier integrity is unclear...
January 6, 2020: Infection and Immunity
#40
JOURNAL ARTICLE
Karin Schreiber, Theodore G Karrison, Steven P Wolf, Kazuma Kiyotani, Madeline Steiner, Eric R Littmann, Eric G Pamer, Thomas Kammertoens, Hans Schreiber, Matthias Leisegang
Burnet postulated that the diversity of T-cell receptors (TCR) allows T cells to protect against the development of cancers that display antigens with a similar, seemingly endless diversity. To test this hypothesis, we developed a strategy in which a single breeding pair of mice gives rise to four groups of sibling mice. Three of the four groups had a similar number of CD8+ T cells, but TCR diversity was either broad, significantly reduced, or absent when expressing only one type of TCR. The fourth group had no T cells...
February 2020: Cancer Immunology Research
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