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2 Materials and methods 2.1 Protocol and registration This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (Moher et al., 2009) and the guidelines from the Cochrane Handbook for Systematic Reviews of Interventions (Higgins and Green, 2008)

Nonetheless, this work has identified novel findings that support future studies to determine whether microbiome changes are contingent upon the combination of both NNMTi and LD switch and mediated through direct NNMTi-driven mechanisms or through indirect mechanisms such as weight or fat loss 8,13

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