Biofloc can be a novel strategy for disease management in contrast to conventional approaches such as antibiotic, antifungal, probiotic and prebiotic application. The "natural probiotic" effect in BFT could act internally and/or externally against, i. e., to Vibrio sp. and ectoparasites, respectively. This effect is promoted by large groups of microorganisms, but mainly bacteria that is considered the first trophic level in the system.

Internally, bacteria and its synthesized compounds could act similar to organic acids and might be effective bio-control agents, also given beneficial host’s microbial balance in the gut [68]. The regular addition of carbon in the water is known to select for polyhydroxyalkanoates (PHA) accumulating bacteria and other groups of bacteria that synthesize PHA granules. The microbial storage product poly-fi-hydroxybutyrate (PHB), a biodegradable polymer belonging to the polyesters class, is only one compound of a whole family of polyhydroxyalkanoates. PHB is produced by a widely variety of microorganisms such as Bacillus sp., Alcaligenes sp., Pseudomonas sp. from soluble organic carbon and is also involved in bacterial carbon metabolism and energy storage [68]. This polymer could comprise ~80% of the bacteria’s cell dry matter and up to 16% on biofloc dry weight [69]. Different carbon sources or structures of carbon substrate will result in varying types of PHA [69].

Such granules are synthesized under conditions of physiological and nutrient stress, i. e., when an essential nutrient like nitrogen is limited in the presence of an excess carbon source [68]. When these polymers are degraded in the gut, they could have antibacterial activity similar to short chain fatty acids (SCFAs) or organic acids. The breakdown of PHA inside the gastrointestinal tract can be carried out via chemical and enzymatic hydrolysis [70].

Chemical hydrolysis can be carried out by treating the polymers with, i. e., NaOH, in which could significantly accelerate its digestibility [70]. On the other hand, enzyme hydrolysis is generally carried out by extracellular depolymerases activities which are widely distributed among bacteria and fungi, acting as a preventive or curative protector against Vibrio sp. infections and stimulate growth and survival of shrimp and fish larvae [69].

The working mechanism of PHAs with respect to their antibacterial activity is not well understood [68]. As they could act similarly to SCFA, some studies speculated the working mechanism by (i) reduction of pH, in which antibacterial activity increases with decreasing pH value [71]; (ii) inhibiting the growth of pathogenic bacteria by interference on cell membrane structure and membrane permeability, as well as instability of internal protons balance, lowering ATP and depletion of cellular energy [72]; and (iii) down-regulate virulence factor expression and positively influence the gut health of animals [73]. Further research is need to maximizing PHA content in bioflocs applied, i. e., for fish/shrimp feed, characterizing and analyzing their bio-control efficacy in different host-microbe systems [68].

Externally, the working mechanism of biofloc microorganisms against pathogens seems to be by competition of space, substrate and nutrients. Some essentials nutrients such as nitrogen are required by both groups (i. e. heterotrophic bacteria vs Vibrio sp.) limiting their growth. Inhibiting compounds excreted by BFT microorganisms, light intensity and type of carbon source also could reduce pathogens growth. Unfortunately, limited information is available on this field. In a study with fish fingerlings [74] was reported that tilapia (initial weight 0.98 ± 0.1g) reared under BFT limited water-exchange condition (FLOC) presented less ectoparasites in gills and ectoderm’s mucous as compared to conventional water — exchange system (CW) after 60 days (Fig 5).