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Page 4 of 13                 Martin et al. Microbiome Res Rep 2023;2:17  https://dx.doi.org/10.20517/mrr.2023.10

               dependant manner [62-64] . Therefore, further studies are required to determine the full scope of its effects.


               Barrier effect and gut dysbiosis
                                                                                         [65]
               Since birth, the gut microbiome influences host responses, shaping the immune system  and contributing
               to organ and tissue development, especially in the gastrointestinal tract (GI) . The gut microbiota is one of
                                                                               [66]
                                                      [67]
               the main contributors to the barrier effect  that prevents the translocation of microbial cells and
               toxins [55,56] . Under normal conditions, the intestinal mucosa creates a dense barrier between the luminal
               compartment and the intestinal epithelium. Other effectors contribute to the barrier effect, such as immune
               cells and cytokines, tight junctions, secretion of antimicrobial peptides (AMPs), and mucins .
                                                                                            [67]

               A healthy equilibrium between the gut microbiota species, its microbial diversity, and its metabolome is
               required for intestinal health, promoting regulatory or anti-inflammatory immune responses [52,65] . In
               contrast, the loss of this equilibrium due to antibiotics or a low-fiber diet results in alterations in the gut
                                                                             [68]
               microbiota composition, a term known as gut dysbiosis [Figure 1] . This microbial condition is
               characterized by different microbial changes , and several studies have highlighted the contribution of gut
                                                     [12]
               dysbiosis to many chronic diseases, including type 2 diabetes, inflammatory bowel diseases (IBD), and
               cardiovascular diseases, and other diseases like neurological conditions, cancer, among others [12-18] .
               Sometimes, gut dysbiosis is characterized by an overabundance of opportunistic pathogens, which in robust
               microbiota have no chance to colonize [61,69,70] . Some examples include toxin-producing gut microbes such as
               Clostridioides difficile, Escherichia coli, or Fusobacterium nucleatum [71,72] . These pathogens are generally
               present in very low numbers in the microbiota; however, certain external conditions favor their growth and
               damaging activities, contributing to colorectal cancer [12,73]  among other diseases. Dysbiosis also can be
               characterized by a depletion in health-associated microorganisms such as BPB, as is the case of IBD [12,61,70] .
               Finally, in some cases, dysbiosis is characterized by a significant rearrangement in the microbiota
               composition, as observed in diarrhea . In many diseases and dysbiotic conditions, there is reduced
                                                [12]
               microbial diversity, usually measured as alpha-diversity [74,75] ; however, a reduced alpha-diversity is not
               always a reliable indicator of disease-associated dysbiosis. In fact, some studies have shown an inconsistent
               relationship between alpha diversity and non-diarrheal diseases [12,76] .


               An imbalance in the gut microbiota, resulting in the loss of beneficial commensal microorganisms or the
               gain of opportunistic pathogens, is often associated with an alteration in the correct functioning of the
                             [77]
               immune system . Gut dysbiosis favors pro-inflammatory systemic immune responses, which may lead to
                                  [78]
               inflammatory diseases . These alterations result in increased permeability, which permits the translocation
               of microbial products and cells, resulting in an impaired gut barrier .
                                                                        [74]
               Bifidobacterium species play an important role in the gut microbiome by contributing to the barrier effect,
               maintaining the balance of the gut microbiome, and preventing pathogenic overgrowth [79-82] . Some species
               within this genus support mucosal integrity, preventing harmful substances from penetrating the body, as
               has been demonstrated for several bifidobacteria [83-87] . The barrier effect is also promoted by certain SCFAs,
               such as acetate and propionate, and by multiple effectors found in these species, such as pili and
               exopolysaccharide [86,88] . Finally, immune modulation by Bifidobacterium promotes balanced immune
               responses and maintains gut homeostasis .
                                                  [89]

               Representative microbial interactions in the gut microbiome
                                                                                             [90]
               Ecological rules dictate microbiome composition, activity, and interactions with the host . As part of a
               complex host-associated ecosystem, the gut microbiome displays emergent properties that differ from those
               of its single constituent species. Competition for nutrients and space, microbial inhibition, and resource
               sharing are common interactions in the gut . Oxygen availability, pH, peristaltic movements, and host
                                                     [25]
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