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Page 12 of 23              Gutierrez et al. Microbiome Res Rep 2023;2:36  https://dx.doi.org/10.20517/mrr.2023.37

               Table 4. Literature review of strain-specific effects of Bifidobacterium species on mucus modulation in the context of inflammation or
               infectious disease
                                                                     Intestinal
                Bifidobacterium species  Finding                               Experimental model     Ref.
                                                                     site
                B. bifidum FL-276.1    Increased MUC2, improved mucus, reduce   Colon  DSS-colitis    [166]
                                       colitis
                B. bifidum FL-228.1    Increased MUC2, improved mucus, reduce   Colon  DSS-colitis    [166]
                                       colitis
                B. bifidum BGN4        Improved mucus, reduce colitis  Colon   DSS-colitis            [168]
                B. longum subsp. longum YS108R  Increased MUC2, improved mucus, reduce   Colon  DSS-colitis  [169]
                                       colitis
                B. longum Bif10        Increased MUC2, improved mucus, reduce   Colon  DSS-colitis    [171]
                                       colitis
                B. breve Bif11         Increased MUC2, improved mucus, reduce   Colon  DSS-colitis    [171]
                                       colitis
                B. breve CBT BR3       Improved mucus, reduce colitis  Colon   DSS-colitis            [170]
                B. animalis subsp. lactis A6  Improved mucus, reduce colitis  Colon  DSS-colitis      [167]
                B. infantis GMCC0460.1  Improved mucus, reduce colitis  Colon  DSS-colitis            [172]
                B. infantis 2017012    Improved mucus, reduce colitis  Colon   DSS-colitis            [176]
                B. infantis unclassified strain  Improved mucus, reduce colitis  Colon  DSS-colitis   [176]
                B. breve H4-2          Improved mucus, reduce colitis  Colon   DSS-colitis            [174]
                B. breve H9-3          Improved mucus, reduce colitis  Colon   DSS-colitis            [174]
                B. lactis BL-99        Improved mucus, reduce colitis  Colon   Zebrafish colitis model  [177]
                B. dentium ATCC 27678  Increased MUC2, improved mucus, reduce   Colon  TNBS-colitis   [96]
                                       colitis
                B. infantis unclassified strain  Improved mucus, reduce colitis  Colon  TNBS-colitis  [178]
                B. longum Bar 33       Improved mucus, reduce colitis  Colon   TNBS-colitis           [176]
                B. animalis subsp. lactis CNCM-  Improved mucus, reduce colitis  Colon  DNBS-colitis  [179]
                I2494
                B. bifidum E3          Increased MUC2, improved mucus  Small intestine LPS-induced injury  [180]
                B. infantis E4         Increased MUC2, improved mucus  Small intestine LPS-induced injury  [180]
                B. lactis BB12         Increased MUC2, improved mucus  Small intestine LPS-induced injury  [180]
                B. bifidum OLB637      Increased mucin expression    Small intestine Rat model of NEC  [181]
                B. bifidum G9-1        Increased MUC2, improved mucus  Small intestine Rotavirus mouse model  [185]
                B. infantis PCM        Improved mucus                Small intestine Cronobacter sakazakii mouse   [186]
                                                                               model


               Colitis-inducing compounds are known to activate ER stress [131-134] , and ER stress has been linked to
               intestinal inflammation in multiple animal models [135-139] . Goblet cells are particularly sensitive to ER stress
               since producing and folding MUC2 is a complex process [140,141] . It has been speculated that modulation of
               goblet cell ER stress by Bifidobacterium species may represent a key pathway by which bifidobacteria
               promote intestinal health. In mucus-producing Caco-2 cells, the application of live B. breve YIT 12272 and
               B. adolescentis YIT 4011T alleviated tunicamycin-induced ER stress . In another study using mucus-
                                                                           [142]
               producing T84 cells, it was shown that B. dentium ATCC 27678-secreted metabolites could also suppress
                                                       [96]
               tunicamycin- or thapsigarin-induced ER stress . Analysis of the B. dentium metabolites revealed that this
               strain generated substantial levels of γ-glutamylcysteine, a compound that can be converted into the
               powerful antioxidant glutathione and suppress oxidative and ER stress [131,133,143-147] . B. dentium metabolites
               harboring γ-glutamylcysteine and application of commmerically available γ-glutamylcysteine both elevated
               glutathione, suppressed inflammatory NF-κB activation, reduced IL-8 secretion, and attenuated the
               induction of the unfolded protein response (UPR) genes GRP78, CHOP, and sXBP1 in T84 cells and TNBS-
               treated mice . These data suggest that Bifidobacterium species can reduce goblet cell ER stress.
                          [96]
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