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\begin{document}

\title{Early-life cytomegalovirus infection is associated with gut microbiota
perturbations and increased risk of atopy}



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


\vspace{-1em}



  
  \date{June 07, 2024}


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\selectlanguage{english}
\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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\textbf{Full title:} \textbf{Early-life cytomegalovirus infection is
associated with gut microbiota perturbations and increased risk of
atopy}

Authors: Hind Sbihi, PhD\textsuperscript{1,7}, Karen E. Simmons,
MSc\textsuperscript{1}, Malcolm R. Sears , MBChB\textsuperscript{2},
Theo J. Moraes, MD PhD\textsuperscript{3}, Allan B. Becker,
MD\textsuperscript{4}, Piush J. Mandhane, MD PhD\textsuperscript{5},
Padmaja Subbarao, MD\textsuperscript{3}, Darlene L.Y.
Dai\textsuperscript{1}, B. Brett Finlay, PhD\textsuperscript{1}, Stuart
E. Turvey, MBBS DPhil\selectlanguage{romanian}\textsuperscript{1ǂ}, Soren
Gantt\textsuperscript{6ǂ}, MD PhD MPH

\textsuperscript{1} University of British Columbia, Vancouver, British
Columbia, Canada

\textsuperscript{2} McMaster University, Hamilton, Ontario, Canada

\textsuperscript{3} Hospital for Sick Children, Toronto, Ontario Canada

\textsuperscript{4} University of Manitoba, Winnipeg, Manitoba, Canada

\textsuperscript{5} University of Alberta, Edmonton, Alberta, Canada

\textsuperscript{6} Universit\selectlanguage{ngerman}é de Montréal, Montréal, Québec, Canada

\textsuperscript{7} BC Centre for Disease Control, Vancouver, British
Columbia, Canada

\selectlanguage{romanian}\textsuperscript{ǂ} These authors contributed equally

\textbf{Running title~:} CMV infection, microbiota and allergies

\textbf{Corresponding authors} :\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
Stuart E. Turvey, MBBS, DPhil, FRCPC & Soren Gantt, MPH, MD,
PhD\tabularnewline
\midrule
\endhead
BC Children's Hospital 950 West 28\textsuperscript{th} Avenue Vancouver,
BC, V5Z 4H4, Canada Phone: 604 875 2345 ext. 3130 Email:
sturvey@cw.bc.ca & Centre de recherche du CHU Sainte-Justine 3175 C\selectlanguage{ngerman}ôte
Sainte-Catherine Montréal (Québec) H3T 1C5, Canada Tél.: 514 345 4931
ext. 5634 Email: soren.gantt.hsj@ssss.gouv.qc.ca\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{ngerman}

\textbf{Word count:} 2398

\textbf{Number of tables:} 2

\textbf{Number of figures:} 3\selectlanguage{english}
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