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Page 4 of 8                  Kumar et al. Microbiome Res Rep 2024;3:37  https://dx.doi.org/10.20517/mrr.2024.28

               Table 1. Prevalence and abundance of Akkermansia muciniphila and Akkermansia massiliensis sp. nov. detected by 16S rRNA
               amplicon sequencing in study cohorts

                                                 Akkermansia muciniphila 1  Akkermansia massiliensis  Co-colonized 3
                                                                                 sp. nov.
                                                                                      2
                Study           Cohort    n    Prevalence   Average    Prevalence   Average     Prevalence
                                               (%)       abundance (%)  (%)       abundance (%)  (%)
                        [11]
                American gut    Crowd-    5,000 47.5     1.0           14.7       0.3           1.3
                                sourced adult
                IsoMic          Healthy adult  52  26.9  0.4           11.5       0.1           1.9
                (NCT05150184)
                NGPs for MH     Lean adult  57  87.7     1.5           26.3       0.3           17.5
                (NCT04229082)
                NGPs for MH     Obese adult  39  82.1    2.0           0.0        0.0           0.0
                (NCT04229082)
               1                                                           2
                Sequence matching V4 region of 16S rRNA of Akkermansia muciniphila strain BAA-835T.  Sequence matching V4 region of 16S rRNA of
                                                    3
               Akkermansia massiliensis sp. nov. strain Marseille-P6666T.  Presence of both Akkermansia muciniphila and Akkermansia massiliensis sp. nov. in the
               same individual. NGPs for MH: Next-generation probiotics for metabolic health.

               At present, there is little known about the possible health effects of Akkermansia species other than
               A. muciniphila. However, Kumar et al. have first described the identification and characterization of a novel
               species of the genus Akkermansia (Akkermansia strain DSM 33459) with beneficial effects in relation to
               metabolic health effects demonstrated in a diet-induced obesity (DIO) mouse model . The genome of this
                                                                                       [13]
               Akkermansia strain DSM 33459 showed 99.85% gANI similarity to the genome of the type strain
               A. massiliensis sp. nov. Marseille-P6666, indicating that strain DSM 33459 also belongs to the proposed
               species A. massiliensis sp. nov. and not to A. muciniphila species based on only 87.5% gANI identity. In the
               DIO model, Akkermansia DSM 33459 administration showed significant improvements in body weight,
               total fat weight, insulin and resistin levels after administration for 12 weeks . Mice consuming the high-fat
                                                                              [13]
               diet also harbored a significantly greater abundance of native A. muciniphila in their intestinal microbiota
               compared to mice on normal chow. Akkermansia DSM 33459 was able to efficiently engraft and replace the
               native A. muciniphila in this model. This further highlights the possible competition of the two
               Akkermansia species, which may limit their co-existence in the gut and questions what mechanisms may be
               at play, such as potential differences in their growth rates, their ability to adhere to intestinal epithelial cells,
               and metabolic pathways related to sulfur reduction . Interestingly, in this mouse DIO study, pasteurized
                                                           [14]
               A. massiliensis sp. nov. did not show the same efficacy as compared to the live bacterium. This observation
               is different compared to what is known for A. muciniphila. Further studies are needed to explore the impact
               of pasteurization methods on the bioactivity of pasteurized A. massiliensis sp. nov.


               In addition, van der Lelie et al. described a consortium of 11 strains (GUT-108), which was designed to
               address gut microbiome dysbiosis in inflammatory bowel disease, and showed that this consortium reversed
                                                [15]
               experimental colitis in a mouse model . One of the 11 strains was named Akkermansia sp. GGCC_0220
               and was suggested to belong to a new Akkermansia species based on gANI. Our analysis of the public whole
               genome deposit record (GenBank Accession: JABFCI000000000.1) for this bacterium indicates that
               Akkermansia GGCC_0220 is 98.7% similar to both A. massiliensis sp. nov. Marseille-P6666 and
               A. massiliensis sp. nov. DSM 33459, i.e., it belongs to the same species.


               AKKERMANSIA  MASSILIENSIS  SP. NOV. - CHARACTERISTICS WITH RELEVANCE FOR
               UNIQUE MECHANISM OF ACTION
               The human gut resident A. muciniphila has gained attention in recent years due to its potential role in
               promoting health. While research on Akkermansia is still progressing, several studies have suggested
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