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Dietary Emulsifier Sodium Stearoyl Lactylate Alters Gut Microbiota in vitro and Inhibits Bacterial Butyrate Producers.
Elmén, L, Zlamal, JE, Scott, DA, Lee, RB, Chen, DJ, Colas, AR, Rodionov, DA, Peterson, SN
Frontiers in microbiology. 2020;:892
Abstract
Dietary emulsifiers are widely used in industrially processed foods, although the effects of these food additives on human gut microbiota are not well studied. Here, we investigated the effects of five different emulsifiers [glycerol monoacetate, glycerol monostearate, glycerol monooleate, propylene glycol monostearate, and sodium stearoyl lactylate (SSL)] on fecal microbiota in vitro. We found that 0.025% (w/v) of SSL reduced the relative abundance of the bacterial class Clostridia and others. The relative abundance of the families Clostridiaceae, Lachnospiraceae, and Ruminococcaceae was substantially reduced whereas that of Bacteroidaceae and Enterobacteriaceae was increased. Given the marked impact of SSL on Clostridia, we used genome reconstruction to predict community-wide production of short-chain fatty acids, which were experimentally assessed by GC-MS analysis. SSL significantly reduced concentrations of butyrate, and increased concentrations of propionate compared to control cultures. The presence of SSL increased lipopolysaccharide, LPS and flagellin in cultured communities, thereby enhancing the proinflammatory potential of SSL-selected bacterial communities.
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Modulatory Effects of Triphala and Manjistha Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study.
Peterson, CT, Pourang, A, Dhaliwal, S, Kohn, JN, Uchitel, S, Singh, H, Mills, PJ, Peterson, SN, Sivamani, RK
Journal of alternative and complementary medicine (New York, N.Y.). 2020;(11):1015-1024
Abstract
Objectives: Triphala (which contains Emblica officinalis, Terminalia bellerica, and Terminalia chebula) and manjistha (Rubia cordifolia), have received increased clinical attention. The aim of the study was to evaluate the effects of triphala, manjistha, or placebo dietary supplementation on gut microbiota as such studies in humans are lacking. Design: This was a 4-week randomized, double-blind, placebo-controlled pilot trial. Setting: This trial was conducted at the University of California Davis, Department of Dermatology. Subjects: A total of 31 healthy human subjects were randomized to 3 groups. Interventions: The 3 groups were instructed to take 2,000 mg of either triphala, manjistha or placebo daily for 4 weeks. Outcome Measures: The impact of treatment on gut microbiota composition was evaluated following a 4-week dietary intervention by profiling fecal communities with 16S rRNA profiling in triphala (n = 9), manjistha (n = 9), or placebo (n = 11) treated subjects that completed the intervention. Results: An average of 336 phylotypes were detected in each sample (range: 161 to 648). The analysis of gut microbiota in placebo control and herb-supplemented participants indicated that responses were highly personalized, and no taxa were uniformly altered by the medicinal herb supplementation protocol. Subjects in both treatment groups displayed a trend toward decreased Firmicutes to Bacteroidetes ratio and increased relative abundance of Akkermansia muciniphila. Both medicinal herb treatments reduced the relative abundance of Rikenellaceae, primarily reflecting changes in Alistipes spp. Conclusions: Dietary supplementation with medicinal herbs altered fecal microbial communities. Despite the lack of a clear response signature, a group of bacterial taxa were identified that were more commonly altered in herb-supplemented participants compared to placebo controls. Clinicaltrials.gov identifier NCT03477825.
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Prebiotic Potential of Herbal Medicines Used in Digestive Health and Disease.
Peterson, CT, Sharma, V, Uchitel, S, Denniston, K, Chopra, D, Mills, PJ, Peterson, SN
Journal of alternative and complementary medicine (New York, N.Y.). 2018;24(7):656-665
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Triphala, licorice and slippery elm are key treatments for gastrointestinal health and disease in traditional systems of medicine. Prebiotics are defined as undigested dietary carbohydrates that alter the gut microbiota and promote human health. They reach the site of action in the colon mostly unmetabolized and are broken down by enzymes. The aim of the study was to find out whether the complex carbohydrates present in herbal medicine may be strong drivers to modulate gut microbiota composition. The study recruited 12 healthy men and women, aged between 30-60 years who had previously followed a vegan or vegetarian diet for more than 1 year, to donate a single stool sample. Results show that both the sugar and protein content of these herbal medicines drive alterations in gut microbiota profiles. Each of these herbal medicines studied, uniquely altered gut bacteria communities. Authors conclude that the health benefits of these herbs are mostly due to their ability to alter the gut microbiota in a manner that is predicted to improve colonic epithelium function, reduce inflammation, and promote protection from bacterial pathogenic infection.
Abstract
INTRODUCTION The prebiotic potential of herbal medicines has been scarcely studied. METHODS The authors therefore used anaerobic human fecal cultivation to investigate whether three herbal medicines commonly used in gastrointestinal health and disease in Ayurveda alter the growth and abundance of specific bacterial species. RESULTS Profiling of cultures supplemented with Glycyrrhiza glabra, Ulmus rubra, or triphala formulation by 16S rDNA sequencing revealed profound changes in diverse taxa in human gut microbiota. Principal coordinate analysis highlights that each herbal medicine drives the formation of unique microbial communities. The relative abundance of approximately one-third of the 299 species profiled was altered by all 3 medicines, whereas additional species displayed herb-specific alterations. Herb supplementation increased the abundance of many bacteria known to promote human health, including Bifidobacterium spp., Lactobacillus spp., and Bacteroides spp. Herb supplementation resulted in the reduced relative abundance of many species, including potential pathogens such as Citrobacter freundii and Klebsiella pneumoniae. Herbal medicines induced blooms of butyrate- and propionate-producing species. U. rubra and triphala significantly increased the relative abundance of butyrate-producing bacteria, whereas G. glabra induced the largest increase in propionate-producing species. To achieve greater insight into the mechanisms through which herbal medicines alter microbial communities, the authors assessed the shifts in abundance of glycosyl hydrolase families induced by each herbal medicine. Herb supplementation, particularly G. glabra, significantly increased the representation and potential expression of several glycosyl hydrolase families. DISCUSSION These studies are novel in highlighting the significant prebiotic potential of medicinal herbs and suggest that the health benefits of these herbs are due, at least in part, to their ability to modulate the gut microbiota in a manner predicted to improve colonic epithelium function, reduce inflammation, and protect from opportunistic infection. Forthcoming studies in human clinical trials will test the concordance of the results generated in vitro and the predictions made by genome analyses.
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Effects of Turmeric and Curcumin Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study.
Peterson, CT, Vaughn, AR, Sharma, V, Chopra, D, Mills, PJ, Peterson, SN, Sivamani, RK
Journal of evidence-based integrative medicine. 2018;:2515690X18790725
Abstract
BACKGROUND Curcuma longa (common name: turmeric) and one of its biologically active constituents, curcumin, have received increased clinical attention. Insufficient data exist on the effects of curcumin and turmeric on the gut microbiota and such studies in humans are lacking. METHODS Turmeric tablets with extract of piperine (Bioperine) (n = 6), curcumin with Bioperine tablets (n = 5), or placebo tablets (n = 3) were provided to healthy human subjects and subsequent changes in the gut microbiota were determined by 16S rDNA sequencing. RESULTS The number of taxa detected ranged from 172 to 325 bacterial species. The placebo group displayed an overall reduction in species by 15%, whereas turmeric-treated subjects displayed a modest 7% increase in observed species posttreatment. Subjects taking curcumin displayed an average increase of 69% in detected species. The gut microbiota response to treatment was highly personalized, thus leading to responders and nonresponders displaying response concordance. These "responsive" subjects defined a signature involving uniform increases in most Clostridium spp., Bacteroides spp., Citrobacter spp., Cronobacter spp., Enterobacter spp., Enterococcus spp., Klebsiella spp., Parabacteroides spp., and Pseudomonas spp. Common to these subjects was the reduced relative abundance of several Blautia spp. and most Ruminococcus spp. CONCLUSIONS All participants' microbiota displayed significant variation over time and individualized response to treatment. Among the responsive participants, both turmeric and curcumin altered the gut microbiota in a highly similar manner, suggesting that curcumin may drive the majority of observed changes observed in turmeric-treated subjects.
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Identification of Altered Metabolomic Profiles Following a Panchakarma-based Ayurvedic Intervention in Healthy Subjects: The Self-Directed Biological Transformation Initiative (SBTI).
Peterson, CT, Lucas, J, John-Williams, LS, Thompson, JW, Moseley, MA, Patel, S, Peterson, SN, Porter, V, Schadt, EE, Mills, PJ, et al
Scientific reports. 2016;:32609
Abstract
The effects of integrative medicine practices such as meditation and Ayurveda on human physiology are not fully understood. The aim of this study was to identify altered metabolomic profiles following an Ayurveda-based intervention. In the experimental group, 65 healthy male and female subjects participated in a 6-day Panchakarma-based Ayurvedic intervention which included herbs, vegetarian diet, meditation, yoga, and massage. A set of 12 plasma phosphatidylcholines decreased (adjusted p < 0.01) post-intervention in the experimental (n = 65) compared to control group (n = 54) after Bonferroni correction for multiple testing; within these compounds, the phosphatidylcholine with the greatest decrease in abundance was PC ae C36:4 (delta = -0.34). Application of a 10% FDR revealed an additional 57 metabolites that were differentially abundant between groups. Pathway analysis suggests that the intervention results in changes in metabolites across many pathways such as phospholipid biosynthesis, choline metabolism, and lipoprotein metabolism. The observed plasma metabolomic alterations may reflect a Panchakarma-induced modulation of metabotypes. Panchakarma promoted statistically significant changes in plasma levels of phosphatidylcholines, sphingomyelins and others in just 6 days. Forthcoming studies that integrate metabolomics with genomic, microbiome and physiological parameters may facilitate a broader systems-level understanding and mechanistic insights into these integrative practices that are employed to promote health and well-being.
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LUD, a new protein domain associated with lactate utilization.
Hwang, WC, Bakolitsa, C, Punta, M, Coggill, PC, Bateman, A, Axelrod, HL, Rawlings, ND, Sedova, M, Peterson, SN, Eberhardt, RY, et al
BMC bioinformatics. 2013;:341
Abstract
BACKGROUND A novel highly conserved protein domain, DUF162 [Pfam: PF02589], can be mapped to two proteins: LutB and LutC. Both proteins are encoded by a highly conserved LutABC operon, which has been implicated in lactate utilization in bacteria. Based on our analysis of its sequence, structure, and recent experimental evidence reported by other groups, we hereby redefine DUF162 as the LUD domain family. RESULTS JCSG solved the first crystal structure [PDB:2G40] from the LUD domain family: LutC protein, encoded by ORF DR_1909, of Deinococcus radiodurans. LutC shares features with domains in the functionally diverse ISOCOT superfamily. We have observed that the LUD domain has an increased abundance in the human gut microbiome. CONCLUSIONS We propose a model for the substrate and cofactor binding and regulation in LUD domain. The significance of LUD-containing proteins in the human gut microbiome, and the implication of lactate metabolism in the radiation-resistance of Deinococcus radiodurans are discussed.
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Comparative omics-driven genome annotation refinement: application across Yersiniae.
Schrimpe-Rutledge, AC, Jones, MB, Chauhan, S, Purvine, SO, Sanford, JA, Monroe, ME, Brewer, HM, Payne, SH, Ansong, C, Frank, BC, et al
PloS one. 2012;(3):e33903
Abstract
Genome sequencing continues to be a rapidly evolving technology, yet most downstream aspects of genome annotation pipelines remain relatively stable or are even being abandoned. The annotation process is now performed almost exclusively in an automated fashion to balance the large number of sequences generated. One possible way of reducing errors inherent to automated computational annotations is to apply data from omics measurements (i.e. transcriptional and proteomic) to the un-annotated genome with a proteogenomic-based approach. Here, the concept of annotation refinement has been extended to include a comparative assessment of genomes across closely related species. Transcriptomic and proteomic data derived from highly similar pathogenic Yersiniae (Y. pestis CO92, Y. pestis Pestoides F, and Y. pseudotuberculosis PB1/+) was used to demonstrate a comprehensive comparative omic-based annotation methodology. Peptide and oligo measurements experimentally validated the expression of nearly 40% of each strain's predicted proteome and revealed the identification of 28 novel and 68 incorrect (i.e., observed frameshifts, extended start sites, and translated pseudogenes) protein-coding sequences within the three current genome annotations. Gene loss is presumed to play a major role in Y. pestis acquiring its niche as a virulent pathogen, thus the discovery of many translated pseudogenes, including the insertion-ablated argD, underscores a need for functional analyses to investigate hypotheses related to divergence. Refinements included the discovery of a seemingly essential ribosomal protein, several virulence-associated factors, a transcriptional regulator, and many hypothetical proteins that were missed during annotation.
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Experimental annotation of post-translational features and translated coding regions in the pathogen Salmonella Typhimurium.
Ansong, C, Tolić, N, Purvine, SO, Porwollik, S, Jones, M, Yoon, H, Payne, SH, Martin, JL, Burnet, MC, Monroe, ME, et al
BMC genomics. 2011;:433
Abstract
BACKGROUND Complete and accurate genome annotation is crucial for comprehensive and systematic studies of biological systems. However, determining protein-coding genes for most new genomes is almost completely performed by inference using computational predictions with significant documented error rates (> 15%). Furthermore, gene prediction programs provide no information on biologically important post-translational processing events critical for protein function. RESULTS We experimentally annotated the bacterial pathogen Salmonella Typhimurium 14028, using "shotgun" proteomics to accurately uncover the translational landscape and post-translational features. The data provide protein-level experimental validation for approximately half of the predicted protein-coding genes in Salmonella and suggest revisions to several genes that appear to have incorrectly assigned translational start sites, including a potential novel alternate start codon. Additionally, we uncovered 12 non-annotated genes missed by gene prediction programs, as well as evidence suggesting a role for one of these novel ORFs in Salmonella pathogenesis. We also characterized post-translational features in the Salmonella genome, including chemical modifications and proteolytic cleavages. We find that bacteria have a much larger and more complex repertoire of chemical modifications than previously thought including several novel modifications. Our in vivo proteolysis data identified more than 130 signal peptide and N-terminal methionine cleavage events critical for protein function. CONCLUSION This work highlights several ways in which application of proteomics data can improve the quality of genome annotations to facilitate novel biological insights and provides a comprehensive proteome map of Salmonella as a resource for systems analysis.