16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.

The prebiotic potential of nervine herbal medicines has been scarcely studied. We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota. Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing revealed profound changes in diverse taxa. Principal coordinate analysis highlights that each herb drives the formation of unique microbial communities predicted to display unique metabolic potential. The relative abundance of approximately one-third of the 243 enumerated species was altered by all herbs. Additional species were impacted in an herb-specific manner. In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring. Collectively, our results indicate that gut microbiota engage in both protein and glycan catabolism, providing amino acid and sugar substrates that are consumed by fermentative species. We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation. Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways. Co-occurrence network analyses identified a large number of taxa pairs in medicinal herb cultures. Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa

Genomics-Based Reconstruction and Predictive Profiling of Amino Acid Biosynthesis in the Human Gut Microbiome

The human gut microbiota (HGM) have an impact on host health and disease. Amino acids are building blocks of proteins and peptides, also serving as precursors of many essential metabolites including nucleotides, cofactors, etc. Many HGM community members are unable to synthesize some amino acids (auxotrophs), while other members possess complete biosynthetic pathways for these nutrients (prototrophs). Metabolite exchange between auxotrophs and prototrophs affects microbial community structure. Previous studies of amino acid biosynthetic phenotypes were limited to model species or narrow taxonomic groups of bacteria. We analyzed over 2800 genomes representing 823 cultured HGM species with the aim to reconstruct biosynthetic pathways for proteinogenic amino acids. The genome context analysis of incomplete pathway variants allowed us to identify new potential enzyme variants in amino acid biosynthetic pathways. We further classified the studied organisms with respect to their pathway variants and inferred their prototrophic vs. auxotrophic phenotypes. A cross-species comparison was applied to assess the extent of conservation of the assigned phenotypes at distinct taxonomic levels. The obtained reference collection of binary metabolic phenotypes was used for predictive metabolic profiling of HGM samples from several large metagenomic datasets. The established approach for metabolic phenotype profiling will be useful for prediction of overall metabolic properties, interactions, and responses of HGM microbiomes as a function of dietary variations, dysbiosis and other perturbations

Alteration of Community Metabolism by Prebiotics and Medicinal Herbs

Several studies have examined the impact of prebiotics on gut microbiota and associated changes in host physiology. Here, we used the in vitro cultivation of human fecal samples stimulated with a series of chemically related prebiotics and medicinal herbs commonly used in Ayurvedic medicine, followed by 16S rRNA sequencing. We applied a genome-wide metabolic reconstruction of enumerated communities to compare and contrast the structural and functional impact of prebiotics and medicinal herbs. In doings so, we examined the relationships between discrete variations in sugar composition and sugar linkages associated with each prebiotic to drive changes in microbiota composition. The restructuring of microbial communities with glycan substrates alters community metabolism and its potential impact on host physiology. We analyzed sugar fermentation pathways and products predicted to be formed and prebiotic-induced changes in vitamin and amino acid biosynthesis and degradation. These results highlight the utility of combining a genome-wide metabolic reconstruction methodology with 16S rRNA sequence-based community profiles to provide insights pertaining to community metabolism. This process also provides a rational means for prioritizing in vivo analysis of prebiotics and medicinal herbs in vivo to test hypotheses related to therapeutic potential in specific diseases of interest

16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.

The prebiotic potential of nervine herbal medicines has been scarcely studied. We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota. Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing revealed profound changes in diverse taxa. Principal coordinate analysis highlights that each herb drives the formation of unique microbial communities predicted to display unique metabolic potential. The relative abundance of approximately one-third of the 243 enumerated species was altered by all herbs. Additional species were impacted in an herb-specific manner. In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring. Collectively, our results indicate that gut microbiota engage in both protein and glycan catabolism, providing amino acid and sugar substrates that are consumed by fermentative species. We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation. Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways. Co-occurrence network analyses identified a large number of taxa pairs in medicinal herb cultures. Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa

16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.

The prebiotic potential of nervine herbal medicines has been scarcely studied. We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota. Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing revealed profound changes in diverse taxa. Principal coordinate analysis highlights that each herb drives the formation of unique microbial communities predicted to display unique metabolic potential. The relative abundance of approximately one-third of the 243 enumerated species was altered by all herbs. Additional species were impacted in an herb-specific manner. In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring. Collectively, our results indicate that gut microbiota engage in both protein and glycan catabolism, providing amino acid and sugar substrates that are consumed by fermentative species. We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation. Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways. Co-occurrence network analyses identified a large number of taxa pairs in medicinal herb cultures. Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa