DOI: 10.5061/dryad.rbnzs7h9w
title: Supplementary files for: How can the MHC mediate social odor via the microbiota community? A deep dive into mechanisms

description: Genes of the major histocompatibility complex (MHC) have long been linked
 to odor signaling and recently researchers’ attention has focused on MHC
 structuring of microbial communities and how this may in turn impact odor.
 However, understanding of the mechanisms through which the MHC could
 affect the microbiota to produce a chemical signal that is both reliable
 and strong enough to ensure unambiguous transmission of behaviorally
 important information remains poor. This is largely because empirical
 studies are rare, predictions are unclear, and the underlying
 immunological mechanisms governing MHC-microbiota interactions are often
 neglected. Here we review the immunological processes involving MHC class
 II (MHC-II) that could affect the commensal community. Focusing on
 immunological and medical research, we provide background knowledge for
 non-immunologists by describing key players within the vertebrate immune
 system relating to MHC-II molecules (which present extracellular-derived
 peptides, and thus interact with extracellular commensal microbes). We
 then systematically review the literature investigating
 MHC-odor-microbiota interactions in animals and identify areas for future
 research. These insights will help to design studies that are able to
 explore the role of MHC-II and the microbiota in the behavior of wild
 populations in their natural environment and consequently propel this
 research area forward.
description: Please
 see 'Supplementary material'-file for detailed supplementary
 methods and results.  
 <b>Systematic review process</b> As we wanted to identify publications that research the interactions between the three components, the MHC, the microbiota, and odor, we carried out a combinatorial approach using search strings that included two of the components in different combinations as well as all three of them together. We conducted the search up to 30<sup>th</sup> January 2020 in both Web of Science and PubMed, excluded reviews, and selected studies written in English. We excluded human studies as the majority focused on single MHC variants or specific microbiota related to diseases. Furthermore, human studies include cultural, technological, and socioeconomic features unique to humans (reviewed in Winternitz and Abbate 2015), such as contraceptives, perfume, and the use of antibiotics, which could influence the microbiota, odor, and behavior of an individual, impeding comparison with other, particularly wild, species. Additionally, we focused on vertebrates only (as non-vertebrates are not relevant for MHC effects) and excluded non-empirical modelling and ex-vivo studies. We excluded studies investigating only a single or genetically modified MHC genotype, except for studies working with knock-out variants, as they enable the investigation of the mechanisms through which the MHC works. In a similar fashion, studies targeting only single microbiota strains were excluded, as these studies do not allow determination of the effects of different MHC genotypes on odor or the microbiota to help unravel the relationship between MHC, odor and microbiota. For studies investigating odor, we excluded those that use preference/discrimination experiments providing more cues to the choosing individual than odor alone as this impedes determination of the role of odor cues. In general, we only kept studies investigating the unidirectional influence of the MHC on the microbiota, of the MHC on odor, and of the microbiota on odor. Studies investigating relationships other than the one-way interactions proposed in Figure 1 have been excluded. For the remaining studies, we recorded study species, MHC locus, odor/microbiota source, methods and study type, hypotheses, results, as well as sample size. <b>Systematic review – search strings</b> We used the following search terms: (MHC OR "major histocompatibility complex") AND (odo$r OR scent OR preen) NOT human (MHC OR "major histocompatibility complex") AND (microbiome OR microbiota) NOT human (odo$r OR scent OR preen) AND (microbiome OR microbiota) NOT human (MHC OR "major histocompatibility complex") AND ((odo$r OR scent OR preen) AND (microbiome OR microbiota)) NOT human <strong>References</strong> Winternitz J, Abbate J. 2015. Examining the evidence for major histocompatibility complex-dependent mate selection in humans and nonhuman primates. Res Rep Biol. doi:10.2147/rrb.s58514.
description: Excel files from systematic review, supplementary material file
 including supplementary methods and results Please see
 'Supplementary material'-file for detailed supplementary methods
 and results.