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Page 2 of 13                 Martin et al. Microbiome Res Rep 2023;2:17  https://dx.doi.org/10.20517/mrr.2023.10

               provide resistance to colonization and gut dysbiosis, highlighting the protective role of Bifidobacterium species.

               Keywords: Bifidobacterium, colonization resistance, gut dysbiosis, microbial interactions




               INTRODUCTION
               The human gut is colonized by a dense community composed of trillions of microorganisms called the gut
                        [1,2]
                                                                                         [3]
               microbiota . Such a high number of microbes influences several aspects of host health . This community
               is dominated by up to 90% of two phyla: Bacteroidota and Bacillota  (formerly Bacteroidetes and
                                                                             [4,5]
                         [6]
               Firmicutes) . Other  phyla,  such  as  Verrucomicrobiota  (Akkermansia  spp.),  Actinomycetota
               (Bifidobacterium spp.), and Pseudomonadota (Escherichia spp.) make a smaller contribution, albeit play
                                             [7,8]
               significant roles in this community . Importantly, each phylum represents dozens of different species and
               strains [9,10] . Most of these microorganisms are commensals, but a small number of opportunistic bacteria can
               cause damage to the host via toxins or pro-inflammatory molecules in some specific situations and
               diseases [11,12] . In addition, other alterations in the microbiome can be associated with various types of
               disorders due to physiological interactions between the microbial community and human host [12-18] .


               Each subject harbors a unique gut microbiota profile that is usually more conserved at the functional than
               taxonomical level . The gut microbiota of any person may be composed of more than 500 different
                               [19]
               microorganisms , making it one of the most complex known microbial communities. The gut microbiota
                             [20]
               shows distinct colonization patterns in newborns , usually dominated by Bifidobacterium species in the
                                                          [21]
               first year of life, shaped by the birth and feeding type . Bifidobacterium is a genus of strict anaerobes,
                                                              [22]
               gram-positive, and fermentative microorganisms, which are usually regarded as safe and beneficial for
               health. Later in life, a plant-based diet switches the microbiota to a more complex community characterized
                                                         [23]
               by both higher species and functional diversity , where Bifidobacterium retains a significant relative
               abundance in the adult human gut as well as its role in health. However, its abundance decreases compared
               to the infant microbiota .
                                   [24]

               Major advances have been made to understand the importance of the gut microbiota in human health. Most
               studies rely on 16S rRNA sequencing to provide the relative abundance profiles of this community, which
               are helpful in estimating microbial diversity . However, these studies only provide a snapshot of the
                                                      [1]
                                                                                     [25]
               community and do not consider the interactions between its constituent members . Why some microbes
               are more abundant than others and coexist with or exclude others are questions without obvious answers.
               Approximately 30,000 interactions between microbes are estimated to occur at a given time . More
                                                                                                  [26]
               complexity is added if we consider that microbes display biogeographical preferences in the gut and are
               present at different abundances and activity levels in different locations [27,28] . Complex microbial interactions
               dictate the composition of the microbiota in great part, but this remains poorly understood .
                                                                                           [29]

               Bifidobacterium plays a pivotal role in the gut microbiota and contributes to health through multiple
               activities and interactions with other gut microbes. This review aims to provide a rationale for how
               microbial activities and microbial interactions, especially those of  Bifidobacterium, contribute to
               colonization resistance and a balanced gut microbiome composition.

               Metabolic activities of gut microbiota and Bifidobacterium
               The gut microbiome is known for its dependence on the diet, where dietary fibers are major drivers in the
               composition of this community . Some microbial groups in the gut are equipped with a wide enzymatic
                                          [30]
               repertoire targeting almost all complex dietary polysaccharides such as pectins, xylans, fructans, starch, and
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