As scientific thought develops then definitions can change. One example of this is the term ‘probiotic’. It was originally defined as a substance produced by one microorganism, that stimulate the growth of another. Later the term was used to describe the microorganism itself and so a strictly functional definition morphed into a function/identity definition. One of the most important attributes of probiotics is in the stimulation of production of short chain fatty acids (SCFAs) which bind to Free Fatty Acid Receptors (FFARs) and this has a number of physiological consequences including, potentially an effect on Alzheimer’s disease and other neurological disorders. The importance of physiological microbiomes in health has been noted. Secondary natural products may interact with microbiomes in different ways including influencing virulence, biofilm formation and the induction of host inflammation. In addition to the effects of exogenous natural products, the physiological microbiome is an important source of endogenous secondary natural products. There are instances of cross talk between quorum sensing systems from different species and kingdoms and this may enhance the establishment of equilibrium states in complex biological systems. One of the potentially most impactful aspects of microbiome manipulation is the induction by natural products of the expression of an enzyme (lactonase) that can break down the potent and widespread bacterial quorum sensing molecule, homoserine lactone. More generally quorum sensing inhibition (QSI) by natural products is an active area of investigation and may be important in finding solutions to anti-microbial resistance (AMR).