Impact of gut colonization with butyrate producing microbiota on respiratory viral infection following allo-HCT

Abstract

Respiratory viral infections are frequent in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) and can potentially progress to lower respiratory tract infection (LRTI). The intestinal microbiota contributes to resistance against viral and bacterial pathogens in the lung. However, whether intestinal microbiota composition and associated changes in microbe-derived metabolites contribute to the risk of LRTI following upper respiratory tract viral infection remains unexplored in the setting of allo-HCT. Fecal samples from 360 allo-HCT patients were collected at the time of stem cell engraftment and subjected to deep, 16S ribosomal RNA gene sequencing to determine microbiota composition, and short-chain fatty acid levels were determined in a nested subset of fecal samples. The development of respiratory viral infections and LRTI was determined for 180 days following allo-HCT. Clinical and microbiota risk factors for LRTI were subsequently evaluated using survival analysis. Respiratory viral infection occurred in 149 (41.4%) patients. Of those, 47 (31.5%) developed LRTI. Patients with higher abundances of butyrate-producing bacteria were fivefold less likely to develop viral LRTI, independent of other factors (adjusted hazard ratio = 0.22, 95% confidence interval 0.04-0.69). Higher representation of butyrate-producing bacteria in the fecal microbiota is associated with increased resistance against respiratory viral infection with LRTI in allo-HCT patients.

Antibiotic Exposure Prior to Respiratory Viral Infection Is Associated with Progression to Lower Respiratory Tract Disease in Allogeneic Hematopoietic Cell Transplant Recipients

“…The epidemiological link observed in the current study may provide rationale to further probe the impact of microbiota on transplant outcomes including respiratory viral disease progression. This premise is consistent with recently published data showing that the abundance of butyrate-producing bacteria is negatively correlated with respiratory viral disease progression [42]. When transplant outcomes are evaluated in future studies of antimicrobial de-escalation strategies, different antibiotic utilization strategies or other strategies modifying the microbiome, respiratory disease progression could be assessed as an important endpoint.…”

Pilot study investigating the effect of enteral and parenteral nutrition on the gastrointestinal microbiome post‐allogeneic transplantation

“…Routine antibiotics during HPCT can result in higher abundance of Proteobacteria or Enterococcus and increased rates of bacteraemia (Taur et al , ). Differences in microbiota composition have also been associated with the development of post‐transplant complications, such as graft‐versus‐host disease (GVHD) (Jenq et al , ; Holler et al , ; Mancini et al , ; Simms‐Waldrip et al , ; Han et al , ), respiratory viral infections (Haak et al , ) and disease relapse (Peled et al , ).…”

Relationship Between Dietary Fiber Intake and Short‐Chain Fatty Acid–Producing Bacteria During Critical Illness: A Prospective Cohort Study

“…In ICU patients, fecal microbial diversity tends to be low on admission and to decline with prolonged hospitalization . In bone marrow transplant recipients, low diversity and low SCFA‐producer levels prior to transplant have been associated with VRE bacteremia, respiratory infections, and increased risk for death …”

“…The primary outcome was the relative abundance of SCFA‐producing bacteria after 72 hours in the ICU based on 16S ribosomal RNA (rRNA) gene sequencing results from the 72‐hour rectal swab. This was defined as the sum total of the relative abundance of the following taxa within clostridial clusters IV/XIVa, with all taxa specified at the lowest possible hierarchical level: Faecalibacterium prausnitzii , Eubacterium rectale , Ruminococcus , Blautia, Coprococcus , and Roseburia . Additional sequencing details are described in the supplementary methods.…”

“…Dietary fiber is a prebiotic that increases the abundance of bacteria producing butyrate and other short‐chain fatty acids (SCFAs). These bacteria, or their metabolites, appear to have immunomodulatory benefits that are relevant for ICU patients . In bone marrow transplant recipients and selective ICU cohorts, increased abundance of SCFA‐producing bacteria was associated with decreased MDR organism colonization, including decreased vancomycin‐resistant Enterococcus (VRE) .…”