on human cells and tissues, such as organoids
( 69 ) and air-liquid interface culture systems
( 70 ), will aid investigation of causalities be-
tween and the microbiome and human dis-
eases (Fig. 3).
Conclusions
Microbiome research at host barriers has changed
the dominant concept that microbes are gen-
erally harmful into a more nuanced under-
standing of the importance of resident microbes
to overall host health. Mounting evidence for
the role that perturbations in the microbiota
play in systemic human disease has generated
great interest in finding microbiota-based ther-
apies. Despite the far greater understanding
that we now have of the pivotal role that the
microbiota of an organism may have in main-
taining health, new approaches are still re-
quired to fully understand the complexities of
temporal and spatial dynamics of the micro-
biota, the interkingdom interactions within
microbial communities,andtheconstantex-
change of signals between the microbiota and
its host.
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ACKNOWLEDGMENTS
We apologize for not being able to cite and highlight all of the
outstanding work in this field. To those entering the field, this
review hopefully serves as a selective guide for how to approach
microbial function and make new discoveries that can answer
pressing public health needs.Funding:Funding is from the NIH,
grants DK122790 and AT009741; the Kenneth Rainin Foundation;
and the Crohn’s & Colitis Foundation.Competing interests:The
authors declare no competing interests.License information:
Copyright © 2022 the authors, some rights reserved; exclusive
licensee American Association for the Advancement of Science. No
claim to original US government works. https://www.science.org/
about/science-licenses-journal-article-reuseSubmitted 21 February 2022; accepted 20 April 2022
10.1126/science.abo2366Lu et al., Science 376 , 950–955 (2022) 27 May 2022 6of6