How do you decide when a microbiome study is ready to publish?

I keep running into the same problem: 16S data look interesting, but I'm never sure whether I've sampled enough sites, timepoints, or controls to make a defensible claim.

Reviewers often ask for more samples or a different sequencing depth after the fact.

How do you decide that a microbiome dataset is complete enough to submit, and what do you do when reviewers want more?