Manipulation of microbiota composition and their metabolites via diet alteration or microbiota engraftment is under intense evaluation in cancer and autoimmune disorders and vaccinology. Learning from our gut endogenous original adjuvants and/or tolerogenic microbes and their metabolites will be critical in overcoming the HIV vaccine challenge [
24]. We recently showed the contribution of dietary tryptophan (Trp), one of the essential amino acids mainly obtained from protein-rich foods, contributed to immune suppression by the production of an immunosuppressive catabolite in the context of HIV/HCV infections [
25‐
27]. Other groups have identified a similar change in cancer, autism, and multiple sclerosis indicating the influence of kynurenine, a metabolite of Trp used in the production of niacin, as an immunosuppressor present in several chronic conditions [
28,
29]. Of note, several Trp metabolites produced by bacteria in the gut are endogenous ligands for the transcription factor aryl hydrocarbon receptor (AhR) which has been recently shown to control B-cell fate decisions including suppression of class switching in vivo after influenza immunization [
30]. AhR activation is linked to both diet and gut microbiota composition and leads to the local production of IL-22, a cytokine that plays an important role in maintaining mucosal immunity and integrity, mainly by innate lymphoid cells group 3 (ILC3) [
31,
32]. Only specific subsets of bacteria, particularly Lactobacilli, an important member of Firmicutes, can metabolize dietary Trp into idole-3-aldehyde to modulate AhR/IL-22 axis, thus contributing to gut mucosal homeostasis [
32,
33]. In addition, AhR activation occurring in macrophages and DCs further contributes to the local anti-inflammatory response.
Certain microbes like
Taenia crassiceps, a parasite that causes a gut helminthic infection, have been shown to impair antibody response to pneumococcal vaccine in mice [
34]. Similarly, Riner et al. showed that immunization against hepatitis B and tetanus toxoid in Kenyan adults having schistosomiasis, caused by members of the Schistosoma genus, resulted in a more rapid decline in antibody titres that can be prevented by a prior anti-helminthic treatment [
35]. All these observations highlight the importance of gut microbial dysbiosis on distal immune response in physiology and disease [
36].