The Impact of Anthelmintic Treatment on Human Gut Microbiota Based on Cross-Sectional and Pre- and Postdeworming Comparisons in Western Kenya

ABSTRACT Murine studies suggest that the presence of some species of intestinal helminths is associated with changes in host microbiota composition and diversity. However, studies in humans have produced varied conclusions, and the impact appears to vary widely depending on the helminth species present. To demonstrate how molecular approaches to the human gut microbiome can provide insights into the complex interplay among disparate organisms, DNA was extracted from cryopreserved stools collected from residents of 5 rural Kenyan villages prior to and 3 weeks and 3 months following albendazole (ALB) therapy. Samples were analyzed by quantitative PCR (qPCR) for the presence of 8 species of intestinal parasites and by MiSeq 16S rRNA gene sequencing. Based on pretreatment results, the presence of neither Ascaris lumbricoides nor Necator americanus infection significantly altered the overall diversity of the microbiota in comparison with age-matched controls. Following ALB therapy and clearance of soil-transmitted helminths (STH), there were significant increases in the proportion of the microbiota made up by Clostridiales (P = 0.0002; average fold change, 0.57) and reductions in the proportion made up by Enterobacteriales (P = 0.0004; average fold change, −0.58). There was a significant posttreatment decrease in Chao1 richness, even among individuals who were uninfected pretreatment, suggesting that antimicrobial effects must be considered in any posttreatment setting. Nevertheless, the helminth-associated changes in Clostridiales and Enterobacteriales suggest that clearance of STH, and of N. americanus in particular, alters the gut microbiota. IMPORTANCE The gut microbiome is an important factor in human health. It is affected by what we eat, what medicines we take, and what infections we acquire. In turn, it affects the way we absorb nutrients and whether we have excessive intestinal inflammation. Intestinal worms may have an important impact on the composition of the gut microbiome. Without a complete understanding of the impact of mass deworming programs on the microbiome, it is impossible to accurately calculate the cost-effectiveness of such public health interventions and to guard against any possible deleterious side effects. Our research examines this question in a “real-world” setting, using a longitudinal cohort, in which individuals with and without worm infections are treated with deworming medication and followed up at both three weeks and three months posttreatment. We quantify the impact of roundworms and hookworms on gut microbial composition, suggesting that the impact is small, but that treatment of hookworm infection results in significant changes. This work points to the need for follow-up studies to further examine the impact of hookworm on the gut microbiota and determine the health consequences of the observed changes.

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Geographical separation and ethnic origin influence the human gut microbial composition: a meta-analysis from a Malaysian perspective

Microbial Genomics ◽

10.1099/mgen.0.000619 ◽

2021 ◽

Vol 7 (8) ◽

Author(s):

Jacky Dwiyanto ◽

Qasim Ayub ◽

Sui Mae Lee ◽

Su Chern Foo ◽

Chun Wie Chong ◽

...

Keyword(s):

Gut Microbiota ◽

Ethnic Groups ◽

Meta Analysis ◽

Ethnic Origin ◽

Rrna Gene ◽

Analysis Model ◽

Human Gut ◽

Microbial Composition ◽

Content Type ◽

Geographical Separation

Ethnicity is consistently reported as a strong determinant of human gut microbiota. However, the bulk of these studies are from Western countries, where microbiota variations are mainly driven by relatively recent migration events. Malaysia is a multicultural society, but differences in gut microbiota persist across ethnicities. We hypothesized that migrant ethnic groups continue to share fundamental gut traits with the population in the country of origin due to shared cultural practices despite subsequent geographical separation. To test this hypothesis, the 16S rRNA gene amplicons from 16 studies comprising three major ethnic groups in Malaysia were analysed, covering 636 Chinese, 248 Indian and 123 Malay individuals from four countries (China, India, Indonesia and Malaysia). A confounder-adjusted permutational multivariate analysis of variance (PERMANOVA) detected a significant association between ethnicity and the gut microbiota (PERMANOVA R 2=0.005, pseudo-F=2.643, P=0.001). A sparse partial least squares – discriminant analysis model trained using the gut microbiota of individuals from China, India and Indonesia (representation of Chinese, Indian and Malay ethnic group, respectively) showed a better-than-random performance in classifying Malaysian of Chinese descent, although the performance for Indian and Malay were modest (true prediction rate, Chinese=0.60, Indian=0.49, Malay=0.44). Separately, differential abundance analysis singled out Ligilactobacillus as being elevated in Indians. We postulate that despite the strong influence of geographical factors on the gut microbiota, cultural similarity due to a shared ethnic origin drives the presence of a shared gut microbiota composition. The interplay of these factors will likely depend on the circumstances of particular groups of migrants.

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Distinct composition and metabolic functions of human gut microbiota are associated with cachexia in lung cancer patients

The ISME Journal ◽

10.1038/s41396-021-00998-8 ◽

2021 ◽

Author(s):

Yueqiong Ni ◽

Zoltan Lohinai ◽

Yoshitaro Heshiki ◽

Balazs Dome ◽

Judit Moldvay ◽

...

Keyword(s):

Lung Cancer ◽

Gut Microbiota ◽

Cancer Patients ◽

Gut Microbiome ◽

Human Gut ◽

Microbial Composition ◽

Shotgun Metagenomics ◽

Lung Cancer Patients ◽

Microbial Species ◽

Functional Pathways

AbstractCachexia is associated with decreased survival in cancer patients and has a prevalence of up to 80%. The etiology of cachexia is poorly understood, and limited treatment options exist. Here, we investigated the role of the human gut microbiome in cachexia by integrating shotgun metagenomics and plasma metabolomics of 31 lung cancer patients. The cachexia group showed significant differences in the gut microbial composition, functional pathways of the metagenome, and the related plasma metabolites compared to non-cachectic patients. Branched-chain amino acids (BCAAs), methylhistamine, and vitamins were significantly depleted in the plasma of cachexia patients, which was also reflected in the depletion of relevant gut microbiota functional pathways. The enrichment of BCAAs and 3-oxocholic acid in non-cachectic patients were positively correlated with gut microbial species Prevotella copri and Lactobacillus gasseri, respectively. Furthermore, the gut microbiota capacity for lipopolysaccharides biosynthesis was significantly enriched in cachectic patients. The involvement of the gut microbiome in cachexia was further observed in a high-performance machine learning model using solely gut microbial features. Our study demonstrates the links between cachectic host metabolism and specific gut microbial species and functions in a clinical setting, suggesting that the gut microbiota could have an influence on cachexia with possible therapeutic applications.

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An Attenuated Salmonella enterica Serovar Typhimurium Strain and Galacto-Oligosaccharides Accelerate Clearance of Salmonella Infections in Poultry through Modifications to the Gut Microbiome

Applied and Environmental Microbiology ◽

10.1128/aem.02526-17 ◽

2017 ◽

Vol 84 (5) ◽

Cited By ~ 17

Author(s):

M. Andrea Azcarate-Peril ◽

Natasha Butz ◽

Maria Belen Cadenas ◽

Matthew Koci ◽

Anne Ballou ◽

...

Keyword(s):

United States ◽

Gut Microbiota ◽

Gut Microbiome ◽

Salmonella Enterica ◽

The United States ◽

Wild Type ◽

Content Type ◽

Salmonella Infections ◽

Serovar Typhimurium ◽

The Impact

ABSTRACT Salmonella is estimated to cause one million foodborne illnesses in the United States every year. Salmonella -contaminated poultry products are one of the major sources of salmonellosis. Given the critical role of the gut microbiota in Salmonella transmission, a manipulation of the chicken intestinal microenvironment could prevent animal colonization by the pathogen. In Salmonella , the global regulator gene fnr ( f umarate n itrate r eduction) regulates anaerobic metabolism and is essential for adapting to the gut environment. This study tested the hypothesis that an attenuated Fnr mutant of Salmonella enterica serovar Typhimurium (attST) or prebiotic galacto-oligosaccharides (GOS) could improve resistance to wild-type Salmonella via modifications to the structure of the chicken gut microbiome. Intestinal samples from a total of 273 animals were collected weekly for 9 weeks to evaluate the impact of attST or prebiotic supplementation on microbial species of the cecum, duodenum, jejunum, and ileum. We next analyzed changes to the gut microbiome induced by challenging the animals with a wild-type Salmonella serovar 4,[5],12:r:− (Nal r ) strain and determined the clearance rate of the virulent strain in the treated and control groups. Both GOS and the attenuated Salmonella strain modified the gut microbiome but elicited alterations of different taxonomic groups. The attST produced significant increases of Alistipes and undefined Lactobacillus , while GOS increased Christensenellaceae and Lactobacillus reuteri . The microbiome structural changes induced by both treatments resulted in a faster clearance after a Salmonella challenge. IMPORTANCE With an average annual incidence of 13.1 cases/100,000 individuals, salmonellosis has been deemed a nationally notifiable condition in the United States by the Centers for Disease Control and Prevention (CDC). Earlier studies demonstrated that Salmonella is transmitted by a subset of animals (supershedders). The supershedder phenotype can be induced by antibiotics, ascertaining an essential role for the gut microbiota in Salmonella transmission. Consequently, modulation of the gut microbiota and modification of the intestinal microenvironment could assist in preventing animal colonization by the pathogen. Our study demonstrated that a manipulation of the chicken gut microbiota by the administration of an attenuated Salmonella strain or prebiotic galacto-oligosaccharides (GOS) can promote resistance to Salmonella colonization via increases of beneficial microorganisms that translate into a less hospitable gut microenvironment.

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Microsporidian Infection in Mosquitoes (Culicidae) Is Associated with Gut Microbiome Composition and Predicted Gut Microbiome Functional Content

Microbial Ecology ◽

10.1007/s00248-021-01944-z ◽

2021 ◽

Author(s):

Artur Trzebny ◽

Anna Slodkowicz-Kowalska ◽

Johanna Björkroth ◽

Miroslawa Dabert

Keyword(s):

16S Rrna ◽

Gut Microbiota ◽

Gut Microbiome ◽

Bacterial Communities ◽

Bacterial Species ◽

Rrna Gene ◽

Microbial Composition ◽

Microbiome Composition ◽

Microsporidian Infection ◽

Functional Content

AbstractThe animal gut microbiota consist of many different microorganisms, mainly bacteria, but archaea, fungi, protozoans, and viruses may also be present. This complex and dynamic community of microorganisms may change during parasitic infection. In the present study, we investigated the effect of the presence of microsporidians on the composition of the mosquito gut microbiota and linked some microbiome taxa and functionalities to infections caused by these parasites. We characterised bacterial communities of 188 mosquito females, of which 108 were positive for microsporidian DNA. To assess how bacterial communities change during microsporidian infection, microbiome structures were identified using 16S rRNA microbial profiling. In total, we identified 46 families and four higher taxa, of which Comamonadaceae, Enterobacteriaceae, Flavobacteriaceae and Pseudomonadaceae were the most abundant mosquito-associated bacterial families. Our data suggest that the mosquito gut microbial composition varies among host species. In addition, we found a correlation between the microbiome composition and the presence of microsporidians. The prediction of metagenome functional content from the 16S rRNA gene sequencing suggests that microsporidian infection is characterised by some bacterial species capable of specific metabolic functions, especially the biosynthesis of ansamycins and vancomycin antibiotics and the pentose phosphate pathway. Moreover, we detected a positive correlation between the presence of microsporidian DNA and bacteria belonging to Spiroplasmataceae and Leuconostocaceae, each represented by a single species, Spiroplasma sp. PL03 and Weissella cf. viridescens, respectively. Additionally, W. cf. viridescens was observed only in microsporidian-infected mosquitoes. More extensive research, including intensive and varied host sampling, as well as determination of metabolic activities based on quantitative methods, should be carried out to confirm our results.

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Probiotics maintain the gut microbiome homeostasis during Indian Antarctic expedition by ship

Scientific Reports ◽

10.1038/s41598-021-97890-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ashish Kumar Srivastava ◽

Vishwajeet Rohil ◽

Brij Bhushan ◽

Malleswara Rao Eslavath ◽

Harshita Gupta ◽

...

Keyword(s):

Placebo Group ◽

Gut Microbiota ◽

Gut Microbiome ◽

Glycoside Hydrolases ◽

Gut Health ◽

Microbial Composition ◽

Carbohydrate Binding Modules ◽

Antarctic Expedition ◽

Probiotic Intervention ◽

The Impact

AbstractShip voyage to Antarctica is a stressful journey for expedition members. The response of human gut microbiota to ship voyage and a feasible approach to maintain gut health, is still unexplored. The present findings describe a 24-day long longitudinal study involving 19 members from 38th Indian Antarctic Expedition, to investigate the impact of ship voyage and effect of probiotic intervention on gut microbiota. Fecal samples collected on day 0 as baseline and at the end of ship voyage (day 24), were analyzed using whole genome shotgun sequencing. Probiotic intervention reduced the sea sickness by 10% compared to 44% in placebo group. The gut microbiome in placebo group members on day 0 and day 24, indicated significant alteration compared to a marginal change in the microbial composition in probiotic group. Functional analysis revealed significant alterations in carbohydrate and amino acid metabolism. Carbohydrate-active enzymes analysis represented functional genes involved in glycoside hydrolases, glycosyltransferases and carbohydrate binding modules, for maintaining gut microbiome homeostasis. Suggesting thereby the possible mechanism of probiotic in stabilizing and restoring gut microflora during stressful ship journey. The present study is first of its kind, providing a feasible approach for protecting gut health during Antarctic expedition involving ship voyage.

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Gut Microbiota Composition Changes in Constipated Women of Reproductive Age

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.557515 ◽

2021 ◽

Vol 10 ◽

Author(s):

Hongxia Li ◽

Jianwei Chen ◽

Xiaojing Ren ◽

Chuanli Yang ◽

Shuai Liu ◽

...

Keyword(s):

Gut Microbiota ◽

Chronic Constipation ◽

Reproductive Age ◽

Rrna Gene ◽

Pathophysiological Mechanism ◽

Healthy Controls ◽

Women Of Reproductive Age ◽

Microbial Composition ◽

Hormone Levels ◽

The Impact

BackgroundChronic constipation is one of the most prevalent functional gastrointestinal disorders, yet its etiology is multifactorial, and the pathophysiological mechanism is still unclear. Previous studies have shown that the gut microbiota of constipated patients differs from healthy controls; however, many discrepancies exist in the findings, and no clear link has been confirmed between chronic constipation and changes in the gut microbiota. Growing evidence indicates that age, gender, and hormone levels can affect the composition of gut microbiota. The aim of this study is to examine the overall changes in gut microbiota within a specific sub-population of patients, namely, constipated women of reproductive age.MethodsWe carried out a cross-sectional study comparing the fecal microbial composition of 30 healthy women and 29 constipated women using 16S rRNA gene sequencing. Only women of reproductive age were recruited to reduce the effects of age, gender, and hormone levels on the microbiome, and to prevent conflating the impact of these factors with the effects of constipation.ResultsThere were obvious differences in the gut microbiota in constipated women of reproductive age compared with the healthy controls, manifesting mainly as a significant increase in the abundance of Bacteroides (p < 0.05) and a significant decrease in the abundance of Proteobacteria (p < 0.01). The overall composition of the gut microbiota in each group was different, which was reflected in the ratios of Firmicutes to Bacteroidetes (F/B), which was 1.52 in the constipated group vs. 2.21 in the healthy group. Additionally, there was a significant decrease in butyrate-producing bacteria, like Roseburia and Fusicatenibacter (p < 0.01).ConclusionThe overall composition of the gut microbiota changed in constipated women of reproductive age, characterized by a loss in Proteobacteria and an increase in Bacteroidetes. Furthermore, the abundance of some butyrate-producing bacteria also reduced. These changes may reflect the unique interactions between host and some bacteria, or some bacterial metabolic products, which may be important targets for future studies to explore the pathogenesis of constipation.

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Natural and after colon washing fecal samples: the two sides of the coin for investigating the human gut microbiome

10.1101/2021.06.29.450302 ◽

2021 ◽

Author(s):

Elisabetta Piancone ◽

Bruno Fosso ◽

Mariangela De Robertis ◽

Elisabetta Notario ◽

Annarita Oranger ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Digital Pcr ◽

Shannon Index ◽

Individual Variability ◽

Rrna Gene ◽

Human Gut ◽

Human Gut Microbiome ◽

Taxonomic Analysis ◽

Paired Samples

To date there are several studies focusing on the importance of gut microbiome for human health, however the selection of a universal sampling matrix representative of the microbial biodiversity associated to the gastrointestinal (GI) tract, still represents a challenge. Here we present a study in which, through a deep metabarcoding analysis of the 16S rRNA gene, we compared two sampling matrices, feces (F) and colonic lavage liquid (LL), in order to evaluate their accuracy to represent the complexity of the human gut microbiome. A training set of 37 volunteers was attained and paired F and LL samples were collected from each subject. A preliminary absolute quantification of total 16S rDNA, performed by droplet digital PCR (ddPCR), confirmed that sequencing and taxonomic analysis were performed on same total bacterial abundance obtained from the two sampling methods. The taxonomic analysis of paired samples revealed that, although specific taxa were predominantly or exclusively observed in LL samples, as well as other taxa were detectable only or were predominant in stool, the microbiomes of the paired samples F and LL in the same subject hold overlapping taxonomic composition. Moreover, LL samples revealed a higher biodiversity than stool at all taxonomic ranks, as demonstrated by the Shannon Index and the Inverse Simpson's Index. We also found greater inter-individual variability than intra-individual variability in both sample matrices. Finally, functional differences were unveiled in the gut microbiome detected in the F and LL samples. A significant overrepresentation of 22 and 13 metabolic pathways, mainly occurring in Firmicutes and Proteobacteria, was observed in gut microbiota detected in feces and LL samples, respectively. This suggests that LL samples may allow for the detection of microbes adhering to the intestinal mucosal surface as members of the resident flora that are not easily detectable in stool, most likely representative of a diet-influenced transient microbiota. This first comparative study on feces and LL samples for the study of the human gut microbiome demonstrates that the use of both types of sample matrices may represent a possible choice to obtain a more complete view of the human gut microbiota in response to different biological and clinical questions.

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Changes in the Gut Microbiome and Predicted Functional Metabolic Effects in an Australian Parkinson’s Disease Cohort

Frontiers in Neuroscience ◽

10.3389/fnins.2021.756951 ◽

2021 ◽

Vol 15 ◽

Author(s):

Jade E. Kenna ◽

Eng Guan Chua ◽

Megan Bakeberg ◽

Alfred Tay ◽

Sarah McGregor ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Gut Microbiota ◽

Gut Microbiome ◽

Metabolic Pathways ◽

Metabolic Effects ◽

Rrna Gene ◽

Microbial Composition ◽

Kegg Analysis ◽

Cohort Differences

Background: There has been increasing recognition of the importance of the gut microbiome in Parkinson’s disease (PD), but the influence of geographic location has received little attention. The present study characterized the gut microbiota and associated changes in host metabolic pathways in an Australian cohort of people with PD (PwP).Methods: The study involved recruitment and assessment of 87 PwP from multiple Movement Disorders Clinics in Australia and 47 healthy controls. Illumina sequencing of the V3 and V4 regions of the 16S rRNA gene was used to distinguish inter-cohort differences in gut microbiota; KEGG analysis was subsequently performed to predict functional changes in host metabolic pathways.Results: The current findings identified significant differences in relative abundance and diversity of microbial operational taxonomic units (OTUs), and specific bacterial taxa between PwP and control groups. Alpha diversity was significantly reduced in PwP when compared to controls. Differences were found in two phyla (Synergistetes and Proteobacteria; both increased in PwP), and five genera (Colidextribacter, Intestinibacter, Kineothrix, Agathobaculum, and Roseburia; all decreased in PwP). Within the PD cohort, there was no association identified between microbial composition and gender, constipation or use of gastrointestinal medication. Furthermore, KEGG analysis identified 15 upregulated and 11 downregulated metabolic pathways which were predicted to be significantly altered in PwP.Conclusion: This study provides the first comprehensive characterization of the gut microbiome and predicted functional metabolic effects in a southern hemisphere PD population, further exploring the possible mechanisms whereby the gut microbiota may exert their influence on this disease, and providing evidence for the incorporation of such data in future individualized therapeutic strategies.

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Inclusion of Konjac Flour in the Gestation Diet Changes the Gut Microbiota, Alleviates Oxidative Stress, and Improves Insulin Sensitivity in Sows

Applied and Environmental Microbiology ◽

10.1128/aem.01374-16 ◽

2016 ◽

Vol 82 (19) ◽

pp. 5899-5909 ◽

Cited By ~ 23

Author(s):

Chengquan Tan ◽

Hongkui Wei ◽

Jiangtao Ao ◽

Guang Long ◽

Jian Peng

Keyword(s):

Oxidative Stress ◽

Insulin Sensitivity ◽

Gut Microbiota ◽

Control Diet ◽

Rrna Gene ◽

Model Assessment ◽

Microbial Composition ◽

Content Type ◽

Konjac Flour ◽

Host Metabolism

ABSTRACTAlthough dietary fibers contribute to health and physiology primarily via the fermentative actions of the gut microbiota of the hosts, few studies have focused on how these interactions influence the metabolic status of sows. Here, the effects of inclusion of konjac flour (KF) in a gestation diet on oxidative stress status, insulin sensitivity, and gut microbiota were investigated to elucidate the correlation between the microbiota and metabolic changes in sows. Sows were assigned to either control or 2.2% KF dietary treatment during gestation. The gut microbiota population in sows during gestation and lactation was assessed by 16S rRNA gene sequencing. The oxidative stress parameters, homeostasis model assessment (HOMA) values, and fatty acids in the blood of sows were also assessed. Compared to the control diet group, KF significantly reduced the serum levels of reactive oxygen species (ROS) and 8-hydroxy-deoxyguanosine (8-OHdG) but increased the serum concentrations of glutathione peroxidase (GSH-Px) in sows on day 1 in lactation. Additionally, sows in the KF group had a lower HOMA insulin resistance value but a higher HOMA insulin sensitivity (HOMA-IS) value. KF induced changes in the gut microbial composition at the phylum and genus levels. The increased relative abundances ofAkkermansiaandRoseburiain the KF group were positively correlated with the HOMA-IS. Overall, dietary KF alleviated oxidative stress and improved insulin sensitivity of sows, and the changes in the gut microbiota in response to KF may have been correlated with the host metabolism response.IMPORTANCETo date, the effect of dietary fiber on metabolism responses and gut microbiota in sows has not been investigated. Here, KF supplementation of a gestation diet in sows was found to alleviate oxidative stress and to improve insulin sensitivity. Pyrosequencing analysis revealed that KF treatment induces changes in the gut microbiota composition at the phylum and genus levels. Moreover, the changes of gut microbiota in response to KF may be correlated with the host metabolism response.

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Abstract MP28: A New Gut Microbial Metabolite Derived From Low Fibre Intake

Hypertension ◽

10.1161/hyp.76.suppl_1.mp28 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Chudan Xu ◽

Michael Nakai ◽

Rikeish Muralitharan ◽

Evany Dinakis ◽

Hamdi Jama ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Mononuclear Cells ◽

Inflammatory Responses ◽

Fold Change ◽

Rrna Gene ◽

Microbial Metabolite ◽

Fibre Intake ◽

High Fibre

Low fermentable fibre intake has emerged as an important risk factor for hypertension through changes in the gut microbiota, but the biological pathways and specific metabolites involved are unknown. We performed untargeted liquid-chromatography mass spectrometry metabolomic profiling on plasma samples from 16 mice fed low or high fibre diets and 70 participants with ambulatory blood pressure recordings. Mouse gut microbiome was analysed using 16S rRNA gene sequencing . In vitro experiments were performed in human peripheral blood mononuclear cells (PBMCs) to assess the role of a new metabolite in inflammatory responses. The phenylalanine, tyrosine and tryptophan biosynthesis pathway was upregulated in hypertensive compared to normotensive participants, as well as in low compared to high fibre fed mice (both q <0.05, pathway impact factor=1.0). In particular, p-cresol glucuronide (pCG), an end-product of tyrosine metabolism, was higher in mice fed with low compared to high fibre in both angiotensin II-treated ( q =4.83 x10 -4 , fold change= 88) and sham groups ( q =1.56 x10 -4 , fold change= 297). pCG is derived from p-Cresol, which is produced by the gut microbiota. β-diversity analyses showed that distinct gut microbiome compositions were associated with levels of pCG in plasma (q<0.05). While diet had a major effect on the gut microbiome (~30%), we found that pCG levels were associated with 5.7-6.3% of the total gut microbiome variation. This is relevant as pCG’s precursor, p-cresol, may inhibit the growth of certain types of bacteria. To understand the possible role of pCG in hypertension, human PBMCs obtained commercially were treated with physiological levels of pCG for 24 hours. This resulted in an increase in proinflammatory IL-17A mRNA ( P =0.01, fold change= 1.79) and a decrease in anti-inflammatory IL-10 mRNA ( P =0.014, fold change= -2.32) when compared to untreated and mock-treated cells. In conclusion, tyrosine biotransformation was associated with both human hypertension and low fibre intake. pCG, a key microbial metabolite derived from the metabolism of tyrosine, was associated with distinct gut microbiome compositions and modulated inflammatory response, suggesting it may be involved in the genesis of hypertension.

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