Elizabeth L. Hohmann

Immunocompromised individuals are at high risk of developing Clostridium difficile-associated disease (CDAD). Fecal microbiota transplantation (FMT) is a highly effective therapy for refractory or recurrent CDAD and, despite safety concerns, has recently been offered to immunocompromised patients. We investigated the genomics of bacterial composition following FMT in immunocompromised patients over a 1-year period. Metagenomic, strain and gene-level bacterial dynamics were characterized in two CDAD-affected hematopoietic stem cell (HCT) recipients following FMT. We found alterations in gene content, including loss of virulence and antibiotic resistance genes. These alterations were accompanied by long-term bacterial divergence at the species and strain levels. Our findings suggest limited durability of the specific bacterial consortium introduced with FMT and indicate that alterations of the functional potential of the microbiome are more complex than can be inferred by taxonomic information alone. Our observation that FMT alone cannot induce long-term donor-like alterations of the microbiota of HCT recipients suggests that FMT cannot indefinitely supersede environmental and/or host factors in shaping bacterial composition.

Immunocompromised individuals are at high risk of developing Clostridium difficile- associated disease (CDAD). Fecal microbiota transplantation (FMT) is a highly effective therapy for refractory or recurrent CDAD and, despite safety concerns, has recently been offered to immunocompromised patients. We investigated the genomics of bacterial composition following FMT in immunocompromised patients over a 1-year period. Metagenomic, strain and gene-level bacterial dynamics were characterized in two CDAD-affected hematopoietic stem cell (HCT) recipients following FMT. We found alterations in gene content, including loss of virulence and antibiotic resistance genes. These alterations were accompanied by long-term bacterial divergence at the species and strain levels. Our findings suggest limited durability of the specific bacterial consortium introduced with FMT and indicate that alterations of the functional potential of the microbiome are more complex than can be inferred by taxonomic information alone. Our observation that FMT alone cannot induce long-term donor-like alterations of the microbiota of HCT recipients suggests that FMT cannot indefinitely supersede environmental and/or host factors in shaping bacterial composition.

The Case Record contributed by Hohmann et al. (Aug. 14 issue),¹ regarding a man with ulcerative colitis in whom bloody diarrhea developed soon after fecal microbiota transplantation (FMT), highlights the difficulty in distinguishing cytomegalovirus (CMV) as a direct cause of disease from its being an “innocent bystander” in patients with CMV infection and active ulcerative colitis. However, the authors also reported an apparent case of diarrheal disease caused by Blastocystis hominis transmitted by means of FMT without describing the complex debate as to whether this organism is a true enteropathogen.

Listeria monocytogenes vectors have shown promise for delivery of viral and tumor antigens in animals. We used two mutant vector strains deleted for actA/plcB (BMB72) and actA/inlB (BMB54), and engineered both strains to secrete a heterologous nucleoprotein antigen from the Influenza A virus. Strains were evaluated in vitro and in mice. Twenty‐two healthy volunteers received single oral doses of either strain in a physiological study of safety, shedding, and immunogenicity. Volunteers were observed in the hospital for seven days and had daily blood cultures, routine safety blood tests (complete blood count with differential; hepatic and renal function), and fecal cultures; none had fever, positive blood cultures, prolonged shedding, or serious or unexpected events. Four of 12 volunteers who received the actA/plcB‐deleted strain had minor, transient, asymptomatic serum transaminase elevations (maximum increase 1.4× upper normal). Six of six volunteers who received ≥4 × 10⁹ colony forming units had detectable mucosal immune responses to listerial antigens, but not to the vectored influenza antigen. Approximately half the volunteers had modest interferon‐γ ELISpot responses to a complex listerial antigen, but none had increases over their baseline responses to the influenza antigen. Comparison with prior work suggests that foreign antigen expression, and perhaps also freezing, may adversely affect the organisms’ immunogenicity.

Intestinal alkaline phosphatase (IAP) is a gut mucosal defense factor known to dephosphorylate lipopolysaccharide (LPS); however, the role of IAP in the gut response to luminal bacteria remains poorly defined. We investigated immune responses of wild-type (WT) and IAP-knockout (IAP-KO) mice to LPS and Salmonella typhimurium challenges.

Previous studies have shown that attenuated salmonellae utilized as vaccine vectors engender strong immune responses; however, balancing immunogenici

Rapid tests for influenza antigen detection are frequently used, but it is not known how receipt of intranasal influenza vaccine affects results of these tests. We tested healthy adults who received either intranasal or intramuscular influenza vaccine. Of the 14 intranasal vaccine recipients, 7 (50%) had a direct fluorescent antibody test (DFA) result and 2 (14%) had an enzyme immunoassay (EIA) result that was positive for influenza antigen within 7 days after vaccination. No subjects had positive EIA results on day 12 or 13 after vaccination. For some intranasal vaccine recipients, rapid influenza-antigen detection tests yield positive results within 1 week after vaccination.