Etary Zn in the Zn(? group; accordingly, this might lead to a depletion in bacterial pathways responsible for Zn uptake, and an enrichment in host mineral absorption pathways for the purpose of improving systemic Zn status. Additionally, lack of Zn available to the bacteria might also cause a decrease in bacterial Zn accumulation. Another aim of our study was to identify correlations between candidate microbes and commonly-used biological indicators of Zn deficiency (Figure 5C). Clostridium indolis, a microbe we found to be negatively correlated with bodyweight and Zn adequacy, has been isolated from clinical samples of both animal and human infections [88], and may have the potential to produce beneficial SCFAs such as acetate and butyrate [89]. Enterococcus sp. was positively correlated with final body weight, serum Zn, and Zn adequacy. Members of this genus, specifically Enterococcus faecium, have been shown previously to correlate with increased bodyweight [90] and elevated serum Fe levels [91]. The presence of Clostridium lactatifermentans, a SCFA producer, positively correlated with bodyweight, serum Zn, and Zn adequacy. It has been isolated previously from Gallus gallus, and associated with an improvement in growth and development (as defined by bodyweight) [92]. Aside from these studies, there are little data linking any of these microbes with a purported influence of host Zn status or overall physiology. Future RG7800 biological activity research using GF animals may elucidate new roles for these specific microbes in the etiology and/or progression of Zn deficiency. 5. Conclusions We have revealed a dramatic compositional and AG-490 biological activity functional remodeling that occurs in the Gallus gallus gut microbiota under chronic Zn deficient conditions. Compositional alterations in bacterial abundance, in part due to host icrobe and microbe icrobe interactions, lead to changes in the functional capacity of the microbiota, such as SCFA output, which can influence the absorption and availability of dietary Zn by the host. Our data suggest that as a consequence of this remodeling, a Zn (? microbiota has the potential to perpetuate, and perhaps even aggravate, the Zn deficient condition through the further sequestration of Zn from the host (Figure 8). Such a microbiota are not functionally compatible with the physiological needs of the Zn deficient host. In addition, others have observed decreased luminal Zn solubility in the intestines [87], increased GI inflammation and intestinal permeability, and an overall decline in GI health [93,94] under Zn deficiency. Our findings add to this knowledge by suggesting possible mechanisms by which the gut microbiota may contribute to host Zn deficiency. Further research should determine whether the gut microbiome could represent a modifiable risk factor for chronic Zn deficiency.Nutrients 2015, 7, 9768?784 Nutrients 2015, 7, page ageFigure 8. Schematic diagram depicting proposed mechanisms by which a Zn deficient gut microbiome Figure 8. Schematic diagram depicting proposed mechanisms by which a Zn deficient gut microbiome may worsen a Zn deficient phenotype. Zn deficiency (1), caused by insufficient dietary Zn (2), induces may worsen a Zn deficient phenotype. Zn deficiency (1), caused by insufficient dietary Zn (2), induces a decrease in gut microbial diversity (3), and an outgrowth of bacteria particularly suited to low Zn a decrease in gut microbial diversity (3), and an outgrowth of bacteria particularly suited to low Zn conditions,.Etary Zn in the Zn(? group; accordingly, this might lead to a depletion in bacterial pathways responsible for Zn uptake, and an enrichment in host mineral absorption pathways for the purpose of improving systemic Zn status. Additionally, lack of Zn available to the bacteria might also cause a decrease in bacterial Zn accumulation. Another aim of our study was to identify correlations between candidate microbes and commonly-used biological indicators of Zn deficiency (Figure 5C). Clostridium indolis, a microbe we found to be negatively correlated with bodyweight and Zn adequacy, has been isolated from clinical samples of both animal and human infections [88], and may have the potential to produce beneficial SCFAs such as acetate and butyrate [89]. Enterococcus sp. was positively correlated with final body weight, serum Zn, and Zn adequacy. Members of this genus, specifically Enterococcus faecium, have been shown previously to correlate with increased bodyweight [90] and elevated serum Fe levels [91]. The presence of Clostridium lactatifermentans, a SCFA producer, positively correlated with bodyweight, serum Zn, and Zn adequacy. It has been isolated previously from Gallus gallus, and associated with an improvement in growth and development (as defined by bodyweight) [92]. Aside from these studies, there are little data linking any of these microbes with a purported influence of host Zn status or overall physiology. Future research using GF animals may elucidate new roles for these specific microbes in the etiology and/or progression of Zn deficiency. 5. Conclusions We have revealed a dramatic compositional and functional remodeling that occurs in the Gallus gallus gut microbiota under chronic Zn deficient conditions. Compositional alterations in bacterial abundance, in part due to host icrobe and microbe icrobe interactions, lead to changes in the functional capacity of the microbiota, such as SCFA output, which can influence the absorption and availability of dietary Zn by the host. Our data suggest that as a consequence of this remodeling, a Zn (? microbiota has the potential to perpetuate, and perhaps even aggravate, the Zn deficient condition through the further sequestration of Zn from the host (Figure 8). Such a microbiota are not functionally compatible with the physiological needs of the Zn deficient host. In addition, others have observed decreased luminal Zn solubility in the intestines [87], increased GI inflammation and intestinal permeability, and an overall decline in GI health [93,94] under Zn deficiency. Our findings add to this knowledge by suggesting possible mechanisms by which the gut microbiota may contribute to host Zn deficiency. Further research should determine whether the gut microbiome could represent a modifiable risk factor for chronic Zn deficiency.Nutrients 2015, 7, 9768?784 Nutrients 2015, 7, page ageFigure 8. Schematic diagram depicting proposed mechanisms by which a Zn deficient gut microbiome Figure 8. Schematic diagram depicting proposed mechanisms by which a Zn deficient gut microbiome may worsen a Zn deficient phenotype. Zn deficiency (1), caused by insufficient dietary Zn (2), induces may worsen a Zn deficient phenotype. Zn deficiency (1), caused by insufficient dietary Zn (2), induces a decrease in gut microbial diversity (3), and an outgrowth of bacteria particularly suited to low Zn a decrease in gut microbial diversity (3), and an outgrowth of bacteria particularly suited to low Zn conditions,.