Corrigendum: Yoga, Meditation and Mind-Body Health: Increased BDNF, Cortisol Awakening Response, and Altered Inflammatory Marker Expression After a 3-Month Yoga and Meditation Retreat.

[This corrects the article DOI: 10.3389/fnhum.2017.00315.].

Community Metabolic Interactions, Vitamin Production and Prebiotic Potential of Medicinal Herbs Used for Immunomodulation.

Historically, the health benefits and immunomodulatory potential of medicinal herbs have been considered an intrinsic quality of the herb itself. We have hypothesized that the health benefits of medicinal herbs may be partially due to their prebiotic potential that alter gut microbiota leading to changes in short chain fatty acids and vitamin production or biotransformation of herb encoded molecules and secondary metabolites. Accumulating studies emphasize the relationship between the gut microbiota and host immune function. While largely unknown, these interactions are mediated by secreted microbial products that activate or repress a variety of immune cell types. Here we evaluated the effect of immunomodulatory, medicinal Ayurvedic herbs on gut microbiota in vitro using 16S rRNA sequencing to assess changes in community composition and functional potential. All immunomodulatory herbs displayed substantial prebiotic potential, targeting unique taxonomic groups. Application of genome reconstruction and analysis of biosynthetic capacity of herb selected communities suggests that many of the 11 herbs tested altered the community metabolism as the result of differential glycan harvest and sugar utilization and secreted products including multiple vitamins, butyrate, and propionate that may impact host physiology and immune function. Taken together, these results provide a useful framework for the further evaluation of these immunomodulatory herbs in vivo to maintain immune homeostasis or achieve desired regulation of immune components in the context of disease.

Modulatory Effects of Triphala and Manjistha Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study.

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.

Prebiotic Potential of Culinary Spices Used to Support Digestion and Bioabsorption.

Although the impact of medicinal and culinary herbs on health and disease has been studied to varying extents, scarcely little is known about the impact of these herbs on gut microbiota and how such effects might contribute to their health benefits. We applied in vitro anaerobic cultivation of human fecal microbiota followed by 16S rRNA sequencing to study the modulatory effects of 4 culinary spices: Curcuma longa (turmeric), Zingiber officinale (ginger), Piper longum (pipli or long pepper), and Piper nigrum (black pepper). All herbs analyzed possessed substantial power to modulate fecal bacterial communities to include potential prebiotic and beneficial repressive effects. We additionally analyzed the sugar composition of each herb by mass spectrometry and conducted genome reconstruction of 11 relevant sugar utilization pathways, glycosyl hydrolase gene representation, and both butyrate and propionate biosynthesis potential to facilitate our ability to functionally interpret microbiota profiles. Results indicated that sugar composition is not predictive of the taxa responding to each herb; however, glycosyl hydrolase gene representation is strongly modulated by each herb, suggesting that polysaccharide substrates present in herbs provide selective potential on gut communities. Additionally, we conclude that catabolism of herbs by gut communities primarily involves sugar fermentation at the expense of amino acid metabolism. Among the herbs analyzed, only turmeric induced changes in community composition that are predicted to increase butyrate-producing taxa. Our data suggests that substrates present in culinary spices may drive beneficial alterations in gut communities thereby altering their collective metabolism to contribute to the salubrious effects on digestive efficiency and health. These results support the potential value of further investigations in human subjects to delineate whether the metabolism of these herbs contributes to documented and yet to be discovered health benefits.

Psychosocial Effects of a Holistic Ayurvedic Approach to Well-being in Health and Wellness Courses.

BACKGROUND: As individuals are increasingly attending health and wellness courses outside of the conventional medical system, there is a need to obtain objective data on the effects of those programs on well-being. METHODS: In total, 154 men and women (mean age 54.7 years; range 25-83) participated in 3 different holistic wellness programs based on Ayurvedic Medicine principles (Seduction of Spirit, Journey into Healing, and Perfect Health) or a vacation control group. Psychosocial outcomes included spirituality (Delaney Spirituality Scale), mindful awareness (Mindful Attention Awareness Scale), psychological flexibility (Acceptance and Action Questionnaire), mood (Center for Epidemiology Studies-Depression), and anxiety (Patient-Reported Outcomes Measurement System Anxiety Scale). RESULTS: Participants in the Seduction of Spirit (P < .004), Journey into Healing (P < .05), and Perfect Health (P < .004) courses showed significant increases in spirituality as compared to vacation controls. Participants in Seduction of Spirit (P < .007) also showed significant increases in mindfulness as compared to vacation controls. Participants in the Seduction of Spirit (P < .001) and Journey into Healing (P < .05) courses showed significant decreases in depressed mood as compared to those in the Perfect Health and vacation control groups. All study participants showed similar increases in psychological flexibility (P < .01) and decreases in anxiety (P < .01). CONCLUSION: Participation in wellness courses that incorporate a mind-body-spirit approach to health improves multiple domains of psychosocial well-being, which persists even after course participation.

Effects of Turmeric and Curcumin Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study.

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.

Yoga, Meditation and Mind-Body Health: Increased BDNF, Cortisol Awakening Response, and Altered Inflammatory Marker Expression after a 3-Month Yoga and Meditation Retreat.

Thirty-eight individuals (mean age: 34.8 years old) participating in a 3-month yoga and meditation retreat were assessed before and after the intervention for psychometric measures, brain derived neurotrophic factor (BDNF), circadian salivary cortisol levels, and pro- and anti-inflammatory cytokines. Participation in the retreat was found to be associated with decreases in self-reported anxiety and depression as well as increases in mindfulness. As hypothesized, increases in the plasma levels of BDNF and increases in the magnitude of the cortisol awakening response (CAR) were also observed. The normalized change in BDNF levels was inversely correlated with BSI-18 anxiety scores at both the pre-retreat (r = 0.40, p < 0.05) and post-retreat (r = 0.52, p < 0.005) such that those with greater anxiety scores tended to exhibit smaller pre- to post-retreat increases in plasma BDNF levels. In line with a hypothesized decrease in inflammatory processes resulting from the yoga and meditation practices, we found that the plasma level of the anti-inflammatory cytokine Interleukin-10 was increased and the pro-inflammatory cytokine Interleukin-12 was reduced after the retreat. Contrary to our initial hypotheses, plasma levels of other pro-inflammatory cytokines, including Interferon Gamma (IFN-γ), Tumor Necrosis Factor (TNF-α), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), and Interleukin-8 (IL-8) were increased after the retreat. Given evidence from previous studies of the positive effects of meditative practices on mental fitness, autonomic homeostasis and inflammatory status, we hypothesize that these findings are related to the meditative practices throughout the retreat; however, some of the observed changes may also be related to other aspects of the retreat such as physical exercise-related components of the yoga practice and diet. We hypothesize that the patterns of change observed here reflect mind-body integration and well-being. The increased BDNF levels observed is a potential mediator between meditative practices and brain health, the increased CAR is likely a reflection of increased dynamic physiological arousal, and the relationship of the dual enhancement of pro- and anti-inflammatory cytokine changes to healthy immunologic functioning is discussed.

Multiplexing and Beyond in Biobehavioral Research.

In contrast to traditional singleplex assays that provide values for only a single analyte in a single biological sample, multiplex assays are a time- and resource-efficient high-throughput approach that provides the opportunity to determine numerous analytes within a single- and small-sample volume. In this editorial on an article by Dorn et al. in this issue of Psychosomatic Medicine, we provide a brief description of the advantages and challenges related to multiplex assays. Although the use of multiplexing as a tool has been relatively limited in biobehavioral research, more recent studies are taking advantage of this technology to obtain deeper insight into regulatory patterns in health and disease states. Multiplex approaches range from several targets to global target profiling that importantly enable unbiased biomarker and pathway discovery.

A Multi-Omic View of Host-Pathogen-Commensal Interplay in Salmonella-Mediated Intestinal Infection.

The potential for commensal microorganisms indigenous to a host (the 'microbiome' or 'microbiota') to alter infection outcome by influencing host-pathogen interplay is largely unknown. We used a multi-omics "systems" approach, incorporating proteomics, metabolomics, glycomics, and metagenomics, to explore the molecular interplay between the murine host, the pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), and commensal gut microorganisms during intestinal infection with S. Typhimurium. We find proteomic evidence that S. Typhimurium thrives within the infected 129/SvJ mouse gut without antibiotic pre-treatment, inducing inflammation and disrupting the intestinal microbiome (e.g., suppressing Bacteroidetes and Firmicutes while promoting growth of Salmonella and Enterococcus). Alteration of the host microbiome population structure was highly correlated with gut environmental changes, including the accumulation of metabolites normally consumed by commensal microbiota. Finally, the less characterized phase of S. Typhimurium's lifecycle was investigated, and both proteomic and glycomic evidence suggests S. Typhimurium may take advantage of increased fucose moieties to metabolize fucose while growing in the gut. The application of multiple omics measurements to Salmonella-induced intestinal inflammation provides insights into complex molecular strategies employed during pathogenesis between host, pathogen, and the microbiome.

Mitochondrial DNA control region sequences from Nairobi (Kenya): inferring phylogenetic parameters for the establishment of a forensic database.

Large forensic mtDNA databases which adhere to strict guidelines for generation and maintenance, are not available for many populations outside of the United States and western Europe. We have established a high quality mtDNA control region sequence database for urban Nairobi as both a reference database for forensic investigations, and as a tool to examine the genetic variation of Kenyan sequences in the context of known African variation. The Nairobi sequences exhibited high variation and a low random match probability, indicating utility for forensic testing. Haplogroup identification and frequencies were compared with those reported from other published studies on African, or African-origin populations from Mozambique, Sierra Leone, and the United States, and suggest significant differences in the mtDNA compositions of the various populations. The quality of the sequence data in our study was investigated and supported using phylogenetic measures. Our data demonstrate the diversity and distinctiveness of African populations, and underline the importance of establishing additional forensic mtDNA databases of indigenous African populations.

Single nucleotide polymorphisms over the entire mtDNA genome that increase the power of forensic testing in Caucasians.

We have sequenced the entire mtDNA genome (mtGenome) of 241 individuals who match 1 of 18 common European Caucasian HV1/HV2 types, to identify sites that permit additional forensic discrimination. We found that over the entire mtGenome even individuals with the same HV1/HV2 type rarely match. Restricting attention to sites that are neutral with respect to phenotypic expression, we have selected eight panels of single nucleotide polymorphism (SNP) sites that are useful for additional discrimination. These panels were selected to be suitable for multiplex SNP typing assays, with 7-11 sites per panel. The panels are specific for one or more of the common HV1/HV2 types (or closely related types), permitting a directed approach that conserves limiting case specimen extracts while providing a maximal chance for additional discrimination. Discrimination provided by the panels reduces the frequency of the most common type in the European Caucasian population from approximately 7% to approximately 2%, and the 18 common types we analyzed are resolved to 105 different types, 55 of which are seen only once.