Secreted small molecules from bacteria, fungi and the human host that affect the microbiome are produced and localized throughout the human body. Cyclic di-GMP is a second messenger ubiquitously produced by bacteria used in signal transduction to regulate functions such as adhesion, biofilm formation, and virulence of pathogens [97]. In the oral microbiome, Porphyromonas gingivalis and Treponema denticola act synergistically to form biofilms in dental plaque [98]. T. denticola produces succinic acid (SA), which serves as a nutrient source for P. gingivalis [99], and isobutyric acid (IBA) from P. gingivalis stimulates the growth of T. denticola. Mutanobactin A, a PKS-NRPS metabolite from Streptococcus mutans that has recently been implicated in regulation of stress tolerance factors, is able to non-lethally affect the fungi Candida albicans [100]. In the gut, Proprionibacterium freudenreichii produces 2-amino-3-carboxy-1,4-naphthoquinone (ACNQ) that stimulates growth of Bifidobacterium longum by serving as an electron transport mediator in the regeneration of NAD+ in the human gastrointestinal tract [101]. Bacterial-produced p-cresol competes as a ligand for sulfating enzymes in the liver, resulting in decreased amounts of the sulfated form of drug metabolites, such as acetaminophen-sulfate, which can alter drug function and toxicity [102].