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\begin{document}

\title{Early-life cytomegalovirus infection is associated with changes in the
intestinal microbiota and increased risk of atopy}



\author[1]{Hind Sbihi}%
\author[1]{Karen Simmons}%
\author[2]{Malcolm Sears}%
\author[3]{Theo Moraes}%
\author[4]{Allen  Becker}%
\author[5]{Piush Mandhane}%
\author[3]{Padmaja Subbarao}%
\author[6]{Darlene Dai}%
\author[7]{B. Brett Finlay}%
\author[1]{Stuart Turvey}%
\author[8]{Soren Gantt}%
\affil[1]{Univ of British Columbia}%
\affil[2]{McMaster University}%
\affil[3]{University of Toronto}%
\affil[4]{University of Manitoba}%
\affil[5]{University of Alberta}%
\affil[6]{British Columbia Children's Hospital}%
\affil[7]{Univ British Columbia}%
\affil[8]{University of Montreal}%


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  \date{May 19, 2024}


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\begin{abstract}
Background: The `old friends' hypothesis posits that reduced exposure to
previously ubiquitous microorganisms is one factor involved in the
increased rates of allergic diseases. Cytomegalovirus (CMV) may be one
of the ``old friends'' hypothesized to help prevent allergic diseases.
We sought to elucidate whether early-life CMV infection is associated
with childhood atopy via perturbations of the gut microbiota. Methods:
Participants were recruited from a population-based birth cohort (CHILD
study) and followed prospectively until age five years in four Canadian
cities. A total of 928 participants provided stool microbiome data,
urine for CMV testing, skin-prick tests, and questionnaires-based
detailed environmental exposures. CMV infection was assessed in the
first year of life while the main outcome was defined by persistent
sensitization to any allergen at ages 1, 3, and 5 years. Results: Early
CMV infection was associated with increased beta and decreased alpha
diversity of the gut microbiota. Both changes in diversity measures and
early CMV infection were associated with persistent allergic
sensitization at age 5 years (aOR= 2.08; 95\%CI: 1, 4.33). Mediation
analysis demonstrated that perturbation of gut microbial composition
explains 30\% of the association. Conclusions: Early-life CMV infection
is associated with an alteration in the intestinal microbiota, which
mediates the effect of the infection on childhood atopy. This work
indicates that preventing CMV infection would not put children at
increased risk of developing atopy. Rather, a CMV vaccine, in addition
to preventing CMV-associated morbidity and mortality, might reduce the
risk of childhood allergic diseases.%
\end{abstract}%



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