scholarly journals Role of gut microbiota in identification of novel TCM-derived active metabolites

2020 ◽  
Author(s):  
Tzu-Lung Lin ◽  
Chia-Chen Lu ◽  
Wei-Fan Lai ◽  
Ting-Shu Wu ◽  
Jang-Jih Lu ◽  
...  

Abstract Traditional Chinese Medicine (TCM) has been extensively used to ameliorate diseases in Asia for over thousands of years. However, owing to a lack of formal scientific validation, the absence of information regarding the mechanisms underlying TCMs restricts their application. After oral administration, TCM herbal ingredients frequently are not directly absorbed by the host, but rather enter the intestine to be transformed by gut microbiota. The gut microbiota is a microbial community living in animal intestines, and functions to maintain host homeostasis and health. Increasing evidences indicate that TCM herbs closely affect gut microbiota composition, which is associated with the conversion of herbal components into active metabolites. These may significantly affect the therapeutic activity of TCMs. Microbiota analyses, in conjunction with modern multiomics platforms, can together identify novel functional metabolites and form the basis of future TCM research.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Alexander Koliada ◽  
Vladislav Moseiko ◽  
Mariana Romanenko ◽  
Oleh Lushchak ◽  
Nadiia Kryzhanovska ◽  
...  

Abstract Background Evidence was previously provided for sex-related differences in the human gut microbiota composition, and sex-specific discrepancy in hormonal profiles was proposed as a main determinant of these differences. On the basis of these findings, the assumption was made on the role of microbiota in the sexual dimorphism of human diseases. To date, sex differences in fecal microbiota were demonstrated primarily at lower taxonomic levels, whereas phylum-level differences between sexes were reported in few studies only. In the present population-based cross-sectional research, sex differences in the phylum-level human gut microbiota composition were identified in a large (total n = 2301) sample of relatively healthy individuals from Ukraine. Results Relative abundances of Firmicutes and Actinobacteria, as determined by qRT-PCR, were found to be significantly increased, while that of Bacteroidetes was significantly decreased in females compared to males. The Firmicutes to Bacteroidetes (F/B) ratio was significantly increased in females compared to males. Females had 31 % higher odds of having F/B ratio more than 1 than males. This trend was evident in all age groups. The difference between sexes was even more pronounced in the elder individuals (50+): in this age group, female participants had 56 % higher odds of having F/B ratio > 1 than the male ones. Conclusions In conclusion, sex-specific differences in the phylum-level intestinal microbiota composition were observed in the Ukraine population. The F/B ratio was significantly increased in females compared to males. Further investigation is needed to draw strong conclusions regarding the mechanistic basis for sex-specific differences in the gut microbiota composition and regarding the role of these differences in the initiation and progression of human chronic diseases.


2020 ◽  
Vol 71 (1) ◽  
pp. 149-161 ◽  
Author(s):  
Ilias Attaye ◽  
Sara-Joan Pinto-Sietsma ◽  
Hilde Herrema ◽  
Max Nieuwdorp

Cardiometabolic disease (CMD), such as type 2 diabetes mellitus and cardiovascular disease, contributes significantly to morbidity and mortality on a global scale. The gut microbiota has emerged as a potential target to beneficially modulate CMD risk, possibly via dietary interventions. Dietary interventions have been shown to considerably alter gut microbiota composition and function. Moreover, several diet-derived microbial metabolites are able to modulate human metabolism and thereby alter CMD risk. Dietary interventions that affect gut microbiota composition and function are therefore a promising, novel, and cost-efficient method to reduce CMD risk. Studies suggest that fermentable carbohydrates can beneficially alter gut microbiota composition and function, whereas high animal protein and high fat intake negatively impact gut microbiota function and composition. This review focuses on the role of macronutrients (i.e., carbohydrate, protein, and fat) and dietary patterns (e.g., vegetarian/vegan and Mediterranean diet) in gut microbiota composition and function in the context of CMD.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Caroline Le Roy ◽  
Ruth Bowyer ◽  
Claire Steves ◽  
Tim Spector ◽  
Bell Jordana

Abstract Objectives Accumulation of visceral fat mass (VFM) is a major risk factor for cardiovascular and metabolic disease. Both gut microbiota and diet have been shown to impact host adiposity in an interdependent manner, but the exact nature of their joint contributions has not been characterised. Here, we aimed to estimate and separate the effect of gut microbiota composition from that of nutrient intake on host VFM in of 1760 older female twins. Methods The gut microbiome profile was assessed by 16S sequencing. VFM was measured by DEXA whole body scan and nutrient intake was assessed through food frequency questionnaires. We used a combination of pair-wise associations, random forest modelling and mediation analysis to separate the effect of the gut microbiota and nutrients on VFM. Results Pairwise analyses revealed that 93 OTUs and 10 nutrients were significantly linked to VFM. Five of the 10 nutrients (fibre, trans fatty acids, magnesium, vitamin E and biotin) were also associated with 23% of the 93 VFM-associated OTUs. To separate the effects of the gut microbiota from nutrients on VFM we carried out conditional analyses. We observed that the majority (87%) of the 93 OTUs remained significantly associated with VFM irrespective of nutrient intake correction. In contrast, we observed that fibre, magnesium, biotin and vitamin E were no longer significantly associated with VFM when adjusting models for OTUs (P > 0.05), implying a role of the gut microbiota in mediating these nutrient effects on VFM. Formal mediation analysis revealed that the individual effect of fibre, biotin, magnesium and vitamin E on VFM were mediated at 69, 43, 41 and 31% respectively by OTUs. Moreover, we estimated that accumulated effect of OTUs on VFM (R2 = 0.19) was twice the one of nutrients (R2 = 0.11) and so were their prediction potential determined using random forest classification. Conclusions Our results suggest that while the role of certain nutrients on VFM appears to depend on gut microbiota composition, specific gut microbes may affect host adiposity regardless of dietary intake. The findings imply that the gut microbiota may have a greater contribution towards shaping host adiposity and VFM, compared to diet alone. Funding Sources We gratefully acknowledge support provided by the JPI HDHL funded DINAMIC consortium (administered by the MRC UK, MR/N030125/1). Supporting Tables, Images and/or Graphs


2010 ◽  
Vol 104 (S2) ◽  
pp. S1-S63 ◽  
Author(s):  
Marcel Roberfroid ◽  
Glenn R. Gibson ◽  
Lesley Hoyles ◽  
Anne L. McCartney ◽  
Robert Rastall ◽  
...  

The different compartments of the gastrointestinal tract are inhabited by populations of micro-organisms. By far the most important predominant populations are in the colon where a true symbiosis with the host exists that is a key for well-being and health. For such a microbiota, ‘normobiosis’ characterises a composition of the gut ‘ecosystem’ in which micro-organisms with potential health benefits predominate in number over potentially harmful ones, in contrast to ‘dysbiosis’, in which one or a few potentially harmful micro-organisms are dominant, thus creating a disease-prone situation. The present document has been written by a group of both academic and industry experts (in the ILSI Europe Prebiotic Expert Group and Prebiotic Task Force, respectively). It does not aim to propose a new definition of a prebiotic nor to identify which food products are classified as prebiotic but rather to validate and expand the original idea of the prebiotic concept (that can be translated in ‘prebiotic effects’), defined as: ‘The selective stimulation of growth and/or activity(ies) of one or a limited number of microbial genus(era)/species in the gut microbiota that confer(s) health benefits to the host.’ Thanks to the methodological and fundamental research of microbiologists, immense progress has very recently been made in our understanding of the gut microbiota. A large number of human intervention studies have been performed that have demonstrated that dietary consumption of certain food products can result in statistically significant changes in the composition of the gut microbiota in line with the prebiotic concept. Thus the prebiotic effect is now a well-established scientific fact. The more data are accumulating, the more it will be recognised that such changes in the microbiota's composition, especially increase in bifidobacteria, can be regarded as a marker of intestinal health. The review is divided in chapters that cover the major areas of nutrition research where a prebiotic effect has tentatively been investigated for potential health benefits. The prebiotic effect has been shown to associate with modulation of biomarkers and activity(ies) of the immune system. Confirming the studies in adults, it has been demonstrated that, in infant nutrition, the prebiotic effect includes a significant change of gut microbiota composition, especially an increase of faecal concentrations of bifidobacteria. This concomitantly improves stool quality (pH, SCFA, frequency and consistency), reduces the risk of gastroenteritis and infections, improves general well-being and reduces the incidence of allergic symptoms such as atopic eczema. Changes in the gut microbiota composition are classically considered as one of the many factors involved in the pathogenesis of either inflammatory bowel disease or irritable bowel syndrome. The use of particular food products with a prebiotic effect has thus been tested in clinical trials with the objective to improve the clinical activity and well-being of patients with such disorders. Promising beneficial effects have been demonstrated in some preliminary studies, including changes in gut microbiota composition (especially increase in bifidobacteria concentration). Often associated with toxic load and/or miscellaneous risk factors, colon cancer is another pathology for which a possible role of gut microbiota composition has been hypothesised. Numerous experimental studies have reported reduction in incidence of tumours and cancers after feeding specific food products with a prebiotic effect. Some of these studies (including one human trial) have also reported that, in such conditions, gut microbiota composition was modified (especially due to increased concentration of bifidobacteria). Dietary intake of particular food products with a prebiotic effect has been shown, especially in adolescents, but also tentatively in postmenopausal women, to increase Ca absorption as well as bone Ca accretion and bone mineral density. Recent data, both from experimental models and from human studies, support the beneficial effects of particular food products with prebiotic properties on energy homaeostasis, satiety regulation and body weight gain. Together, with data in obese animals and patients, these studies support the hypothesis that gut microbiota composition (especially the number of bifidobacteria) may contribute to modulate metabolic processes associated with syndrome X, especially obesity and diabetes type 2. It is plausible, even though not exclusive, that these effects are linked to the microbiota-induced changes and it is feasible to conclude that their mechanisms fit into the prebiotic effect. However, the role of such changes in these health benefits remains to be definitively proven. As a result of the research activity that followed the publication of the prebiotic concept 15 years ago, it has become clear that products that cause a selective modification in the gut microbiota's composition and/or activity(ies) and thus strengthens normobiosis could either induce beneficial physiological effects in the colon and also in extra-intestinal compartments or contribute towards reducing the risk of dysbiosis and associated intestinal and systemic pathologies.


2019 ◽  
Author(s):  
Inês Coelho ◽  
Nádia Duarte ◽  
Maria Paula Macedo ◽  
Carlos Penha-Gonçalves

AbstractThe involvement of gut microbiota in liver disease has been addressed in the context of the “leaky gut hypothesis” postulating that dysbiosis allow microbial components to elicit liver inflammatory responses and hepatic tissue damage. Conversely, commensal gut microbiota acting on innate immune receptors protect against hepatotoxic insults. Given that mice deficient for the triggering receptor expressed on myeloid cells-2 (Trem-2) show increased vulnerability to experimental drug-induced hepatic damage we explored the possibility that Trem-2 is a modulator of gut microbiota composition.We found that microbiota composition in untreated Trem-2 KO mice differs from the wild-type showing overall decrease in microbiota diversity and increased representation of Verrucomicrobia. Interestingly, induction of liver damage with hepatotoxic drugs blunted this microbiota diversity difference and altered phyla composition with increased representation of Verrucomicrobia during acute hepatic injury and Proteobacteria during chronic challenge. Furthermore, co-housing experiments that homogenized microbiota diversity showed that the increased liver tissue vulnerability to hepatotoxic insults in Trem-2 KO mice was not dependent on microbiota composition. This work uncouples Trem-2 dependent alterations in gut commensal microbiota from Trem-2 pro-recovery effects in the damaged liver tissue. These findings support the possibility that unlinked actions of innate immune receptors contribute to disease association with microbiota alterations, particularly with the Verrucomicrobia phylum.ImportanceTrem-2 is a mammalian innate immunity receptor involved in development and resolution of tissue damage, namely in the brain and in the liver. Nevertheless, it is not known whether gut microbiota is contributing to these Trem-2 mediated phenotypes. We found that Trem-2 KO mice spontaneously display different gut microbiota composition as compared to wild-type mice, namely with increased abundance of the phylum Verrucomicrobia. Notably these differences do not impact the control of Trem-2 on liver tissue vulnerability to hepatotoxic insults. This work uncouples Trem-2 modulation of gut microbiota and the role of Trem-2 on responses to liver damage. This work brings new insights on role of innate immune receptors on the association of organic and systemic diseases with gut microbiota.


Genes ◽  
2019 ◽  
Vol 10 (4) ◽  
pp. 270 ◽  
Author(s):  
Ce Yuan ◽  
Clifford J. Steer ◽  
Subbaya Subramanian

Changes in gut microbiota composition have consistently been observed in patients with colorectal cancer (CRC). Yet, it is not entirely clear how the gut microbiota interacts with tumor cells. We know that tumor cells undergo a drastic change in energy metabolism, mediated by microRNAs (miRNAs), and that tumor-derived miRNAs affect the stromal and immune cell fractions of the tumor microenvironment. Recent studies suggest that host intestinal miRNAs can also affect the growth and composition of the gut microbiota. Our previous CRC studies showed a high-level of interconnectedness between host miRNAs and their microbiota. Considering all the evidence to date, we postulate that the altered nutrient composition and miRNA expression in the CRC microenvironment selectively exerts pressure on the surrounding microbiota, leading to alterations in its composition. In this review article, we present our current understanding of the role of miRNAs in mediating host–microbiota interactions in CRC.


Microbiome ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Jordi Mayneris-Perxachs ◽  
María Arnoriaga-Rodríguez ◽  
Diego Luque-Córdoba ◽  
Feliciano Priego-Capote ◽  
Vicente Pérez-Brocal ◽  
...  

Abstract Background Gonadal steroid hormones have been suggested as the underlying mechanism responsible for the sexual dimorphism observed in metabolic diseases. Animal studies have also evidenced a causal role of the gut microbiome and metabolic health. However, the role of sexual dimorphism in the gut microbiota and the potential role of the microbiome in influencing sex steroid hormones and shaping sexually dimorphic susceptibility to disease have been largely overlooked. Although there is some evidence of sex-specific differences in the gut microbiota diversity, composition, and functionality, the results are inconsistent. Importantly, most of these studies have not taken into account the gonadal steroid status. Therefore, we investigated the gut microbiome composition and functionality in relation to sex, menopausal status, and circulating sex steroids. Results No significant differences were found in alpha diversity indices among pre- and post-menopausal women and men, but beta diversity differed among groups. The gut microbiota from post-menopausal women was more similar to men than to pre-menopausal women. Metagenome functional analyses revealed no significant differences between post-menopausal women and men. Gonadal steroids were specifically associated with these differences. Hence, the gut microbiota of pre-menopausal women was more enriched in genes from the steroid biosynthesis and degradation pathways, with the former having the strongest fold change among all associated pathways. Microbial steroid pathways also had significant associations with the plasma levels of testosterone and progesterone. In addition, a specific microbiome signature was able to predict the circulating testosterone levels at baseline and after 1-year follow-up. In addition, this microbiome signature could be transmitted from humans to antibiotic-induced microbiome-depleted male mice, being able to predict donor’s testosterone levels 4 weeks later, implying that the microbiota profile of the recipient mouse was influenced by the donor’s gender. Finally, obesity eliminated most of the differences observed among non-obese pre-menopausal women, post-menopausal women, and men in the gut microbiota composition (Bray-Curtis and weighted unifrac beta diversity), functionality, and the gonadal steroid status. Conclusions The present findings evidence clear differences in the gut microbial composition and functionality between men and women, which is eliminated by both menopausal and obesity status. We also reveal a tight link between the gut microbiota composition and the circulating levels of gonadal steroids, particularly testosterone.


Gut ◽  
2021 ◽  
pp. gutjnl-2020-322599
Author(s):  
Hsin-Chih Lai ◽  
Tzu-Lung Lin ◽  
Ting-Wen Chen ◽  
Yu-Lun Kuo ◽  
Chih-Jung Chang ◽  
...  

ObjectiveChronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.DesignA murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.ResultsGut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.ConclusionThe gut microbiota–lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.


2017 ◽  
Vol 12 (1) ◽  
Author(s):  
Marianna Roselli ◽  
Chiara Devirgiliis ◽  
Paola Zinno ◽  
Barbara Guantario ◽  
Alberto Finamore ◽  
...  

mBio ◽  
2014 ◽  
Vol 5 (5) ◽  
Author(s):  
Johan Dicksved ◽  
Patrik Ellström ◽  
Lars Engstrand ◽  
Hilpi Rautelin

ABSTRACTThe gut microbiota is essential for human health, but very little is known about how the composition of this ecosystem can influence and respond to bacterial infections. Here we address this by prospectively studying the gut microbiota composition before, during, and after naturalCampylobacterinfection in exposed poultry abattoir workers. The gut microbiota composition was analyzed with 16S amplicon sequencing of fecal samples from poultry abattoir workers during the peak season ofCampylobacterinfection in Sweden. The gut microbiota compositions were compared between individuals who became culture positive forCampylobacterand those who remained negative. Individuals who becameCampylobacterpositive had a significantly higher abundance ofBacteroides(P= 0.007) andEscherichia(P= 0.002) species than those who remained culture negative. Furthermore, this group had a significantly higher abundance ofPhascolarctobacterium(P= 0.017) andStreptococcus(P= 0.034) sequences than theCampylobacter-negative group, which had an overrepresentation ofClostridiales(P= 0.017), unclassifiedLachnospiraceae(P= 0.008), andAnaerovorax(P= 0.015) sequences. Intraindividual comparisons of the fecal microbiota compositions yielded small differences over time inCampylobacter-negative participants, but significant long-term changes were found in theCampylobacter-positive group (P< 0.005). The results suggest that the abundance of specific genera in the microbiota reduces resistance toCampylobactercolonization in humans and thatCampylobacterinfection can have long-term effects on the composition of the human fecal microbiota.IMPORTANCEStudies using mouse models have made important contributions to our understanding of the role of the gut microbiota in resistance to bacterial enteropathogen colonization. The relative abundances ofEscherichia coliandBacteroidesspecies have been pointed out as important determinants of susceptibility to Gram-negative pathogens in general andCampylobacterinfection in particular. In this study, we assessed the role of the human gut microbiota in resistance toCampylobactercolonization by studying abattoir workers that are heavily exposed to these bacteria. Individuals with a certain composition of the gut microbiota became culture positive forCampylobacter. As their microbiotas were characterized by high abundances ofBacteroidesspp. andE. coli, well in line with the findings with mouse models, these bacterial species likely play an important role in colonization resistance also in humans.


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