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Page 8 of 20                Horwell et al. Microbiome Res Rep 2025;4:1    https://dx.doi.org/10.20517/mrr.2024.32

               microbiome, although there have been no epidemiological studies assessing if this makes any difference to
                           [125]
               human health .
               Therefore, it is perhaps surprising that despite the significant time spent in the home environment, several
               studies have found that it is only responsible for a small proportion of the variation seen in the infant’s
               microbiome [126,127] . One study looked at adopted children and compared their microbiome to their
                                                                                                       [128]
               genetically unrelated siblings and found that the shared home environment explained 6% of the variance .
               The number of occupants in the shared house (i.e., how many siblings or parents cohabit in the house) has
               also failed to provide consistent results for any effect on the microbiome, although the presence of older
               siblings appears to alter the rate of maturation of the infant microbiome [127,129] . To add to the complexity that
               researchers face in trying to elucidate environment variables that affect microbiomic dynamics, twin studies
               have demonstrated increased concordance among monozygotic compared to dizygotic twins, showing that
                                                      [130]
               there is a genetic influence on the microbiome . For example, the LCT, Fut2, irak4, and Nod2 genes have

               been directly linked to an alteration in the abundance of Bifidobacterium, Lachnospiraceae, Roseburia,
               Bacteroidetes, and Firmicutes, respectively [131-134] . This, in part, explains why genetic mutations (e.g., in Nod2)
               causing perturbations in the microbiome might be pathogenic for IBD [132,135] .

               Although no consistent effect has been found on the microbiome of adults , household pets modulate the
                                                                              [136]
               microbiome of children . Specifically, Bifidobacterium is increased in children with household dogs .
                                    [137]
                                                                                                      [137]
               Having a dog in the house during infancy reduces the risk of childhood asthma, an atopic disease that
                                                                  [137]
               appears to have an inverse relationship with Bifidobacterium . A recent meta-analysis using cohort studies
               of children with household dogs adds weight to this, with a risk reduction for asthma of 0.85 (95%CI = 0.73-
               0.97) . Interestingly, there appears to be a “dose response” with this association, with one study showing
                   [138]
                                                                      [139]
               that two or more dogs had a greater effect than a single dog . While we believe that the prevailing
               evidence supports household dogs being protective, albeit with potentially a small clinical effect, there is still
               conflicting evidence in the literature. As an example, one meta-analysis using a mix of cohort and case-
               control data came to an antithetical conclusion .
                                                      [140]

               Day care
               Children attending day care facilities are exposed to a group of peers with different microbiomes during
               their dynamic period of colonisation. One study found that compared to homeschooled children, day care
               resulted in a significantly more diverse and abundant microbiome, with an increased abundance in
                                                                      [141]
               Bacteroidetes, Firmicutes, Lachnospiraceae, and  Ruminococcaceae . Perhaps  unsurprisingly,  the  same
               group found that the microbiomes of peers at individual day care centres become more similar to each other
               compared to children in separate facilities. Previous studies have noted that the mixing of children in day
               care facilities is inversely related to childhood diabetes, suggesting that the microbiome might influence the
               pathogenesis . Taken together, it appears that the mixing of children from outside of the household has a
                          [142]
               larger effect on the microbiome than mixing within the household; this is presumed to be due to the relative
               homogeneity between parents and offspring compared to the more diverse microbiomes of multiple
               classmates.

               Geographical proximity to the natural environment
                                                                   [143]
               There is significant heterogeneity between global populations ; for example, populations living in agrarian
               societies  generally  have  a  higher  abundance  of  Bacillus, Clostriales, Prevotella, Proteobacteria,
               Ruminobacter, Spirochaetes, and Succinivibrionaceae, while that of modern urban populations have higher
               Bacteroides, Bifidobacterium, Blautia, and  Firmicutes [144-146] . However,  elucidating  if  this  is  due  to  the
               geography of nations (e.g., urban USA vs. rural Malawi) or their respective diet, cultural habits, and climate,
               among others, has proved hard to determine. One review has noted that even within individual nations,
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