Exploratory analysis of covariation of microbiota-derived vitamin K and cognition in older adults

ABSTRACT Background Vitamin K has multiple important physiological roles, including blood coagulation and beneficial effects on myelin integrity in the brain. Some intestinal microbes possess the genes to produce vitamin K in the form of menaquinone (MK). MK appears in higher concentration in tissues, such as the brain, particularly MK4, than the dietary form of phylloquinone (PK). Lower PK concentrations have been reported in patients with Alzheimer disease while higher serum PK concentrations have been positively associated with verbal episodic memory. Despite knowledge of the importance of vitamin K for various health parameters, few studies have measured MK concentration and biosynthesis by gut commensals. Objective The aim of the current study was to investigate the relation between genes involved in gut-microbiota derived MK, concentrations of MK isoforms, and cognitive function. Methods Shotgun metagenomic sequencing of the gut microbiome of 74 elderly individuals with different cognitive ability levels was performed. From this, gene counts for microbial MK biosynthesis were determined. Associations between clusters of individuals, grouped based on a similar presence and prevalence of MK biosynthesis genes, and cognitive ability were investigated. Fecal MK concentrations were quantified by HPLC to investigate correlations with subject clusters. Results Separation of subject groups defined by banded quantification of the genetic potential of their microbiome to biosynthesize MK was associated with significant differences in cognitive ability [assessed using the Mini-Mental State Examination (MMSE)]. Three MK isoforms were found to be positively associated with MMSE, along with the identification of key components of the MK pathway that drive this association. Although the causality and direction of these associations remain unknown, these findings justify further studies. Conclusions This study provides evidence that although total concentrations of MK did not covary with cognition, certain MK isoforms synthesized by the gut microbiome, particularly the longer chains, are positively associated with cognition.

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Administration of Bifidobacterium breve Improves the Brain Function of Aβ1-42-Treated Mice via the Modulation of the Gut Microbiome

Nutrients ◽

10.3390/nu13051602 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1602

Author(s):

Guangsu Zhu ◽

Jianxin Zhao ◽

Hao Zhang ◽

Wei Chen ◽

Gang Wang

Keyword(s):

Gut Microbiome ◽

Dietary Intervention ◽

Neuroprotective Effects ◽

Bifidobacterium Breve ◽

Beneficial Effects ◽

Behavioral Abnormalities ◽

Fibronectin Type Iii ◽

Fibronectin Type Iii Domain ◽

The Brain ◽

Fibronectin Type

Psychobiotics are used to treat neurological disorders, including mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, the mechanisms underlying their neuroprotective effects remain unclear. Herein, we report that the administration of bifidobacteria in an AD mouse model improved behavioral abnormalities and modulated gut dysbiosis. Bifidobacterium breve CCFM1025 and WX treatment significantly improved synaptic plasticity and increased the concentrations of brain-derived neurotrophic factor (BDNF), fibronectin type III domain-containing protein 5 (FNDC5), and postsynaptic density protein 95 (PSD-95). Furthermore, the microbiome and metabolomic profiles of mice indicate that specific bacterial taxa and their metabolites correlate with AD-associated behaviors, suggesting that the gut–brain axis contributes to the pathophysiology of AD. Overall, these findings reveal that B. breve CCFM1025 and WX have beneficial effects on cognition via the modulation of the gut microbiome, and thus represent a novel probiotic dietary intervention for delaying the progression of AD.

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Yoghurt Consumption is Associated With Transient Changes in the Composition of the Human Gut Microbiome

10.21203/rs.3.rs-99718/v1 ◽

2020 ◽

Author(s):

Caroline Ivanne Le Roy ◽

Alexander Kurilshikov ◽

Emily Leeming ◽

Alessia Visconti ◽

Ruth Bowyer ◽

...

Keyword(s):

16S Rrna ◽

Gut Microbiota ◽

Visceral Fat ◽

Gut Microbiome ◽

Body Weight Gain ◽

Healthy Eating Index ◽

Rrna Gene ◽

Metagenomic Sequencing ◽

Sequencing Data ◽

Shotgun Metagenomic Sequencing

Abstract Background: Yoghurt contains live bacteria that could contribute via modulation of the gut microbiota to its reported beneficial effects such as reduced body weight gain and lower incidence of type 2 diabetes. To date, the association between yoghurt consumption and the composition of the gut microbiota is underexplored. Here we used clinical variables, metabolomics, 16S rRNA and shotgun metagenomic sequencing data collected on over 1000 predominantly female UK twins to define the link between the gut microbiota and yoghurt-associated health benefits. Results: According to food frequency questionnaires (FFQ), 73% of subjects consumed yoghurt. Consumers presented a healthier diet pattern (healthy eating index: beta = 2.17±0.34; P = 2.72x10-10) and improved metabolic health characterised by reduced visceral fat (beta = -28.18±11.71 g; P = 0.01). According to 16S rRNA gene analyses and whole shotgun metagenomic sequencing approach consistent taxonomic variations were observed with yoghurt consumption. More specifically, we identified higher abundance of species used as yoghurt starters Streptococcus thermophilus (beta = 0.41±0.051; P = 6.14x10-12) and sometimes added Bifidobacterium animalis subsp. lactis (beta = 0.30±0.052; P = 1.49x10-8) in the gut of yoghurt consumers. Replication in 1103 volunteers from the LifeLines-DEEP cohort confirmed the increase of S. thermophilus among yoghurt consumers. Using food records collected the day prior to faecal sampling we showed that increase in these two yoghurt bacteria could be transient. Metabolomics analysis revealed that B. animalis subsp. lactis was associated with 13 faecal metabolites including a 3-hydroxyoctanoic acid, known to be involved in the regulation of gut inflammation.Conclusions: Yoghurt consumption is associated with reduced visceral fat mass and changes in gut microbiome including transient increase of yoghurt-contained species (i.e. S. thermophilus and B. lactis).

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The gut microbiome in konzo

Nature Communications ◽

10.1038/s41467-021-25694-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Matthew S. Bramble ◽

Neerja Vashist ◽

Arthur Ko ◽

Sambhawa Priya ◽

Céleste Musasa ◽

...

Keyword(s):

Gut Microbiome ◽

Bacterial Species ◽

Sub Saharan Africa ◽

Metagenomic Sequencing ◽

Childbearing Age ◽

Shotgun Metagenomic Sequencing ◽

Republic Of The Congo ◽

Study Population ◽

Sub Saharan ◽

Insight Into

AbstractKonzo, a distinct upper motor neuron disease associated with a cyanogenic diet and chronic malnutrition, predominately affects children and women of childbearing age in sub-Saharan Africa. While the exact biological mechanisms that cause this disease have largely remained elusive, host-genetics and environmental components such as the gut microbiome have been implicated. Using a large study population of 180 individuals from the Democratic Republic of the Congo, where konzo is most frequent, we investigate how the structure of the gut microbiome varied across geographical contexts, as well as provide the first insight into the gut flora of children affected with this debilitating disease using shotgun metagenomic sequencing. Our findings indicate that the gut microbiome structure is highly variable depending on region of sampling, but most interestingly, we identify unique enrichments of bacterial species and functional pathways that potentially modulate the susceptibility of konzo in prone regions of the Congo.

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Interplay between the human gut microbiome and host metabolism

10.1101/561787 ◽

2019 ◽

Cited By ~ 1

Author(s):

Alessia Visconti ◽

Caroline I. Le Roy ◽

Fabio Rosa ◽

Niccolo Rossi ◽

Tiphaine C. Martin ◽

...

Keyword(s):

Gut Microbiome ◽

Metabolic Pathways ◽

Taxonomic Composition ◽

Metagenomic Sequencing ◽

Human Gut ◽

Metabolic Potential ◽

Microbial Ecosystem ◽

Microbiome Composition ◽

Shotgun Metagenomic Sequencing ◽

Key Species

AbstractThe human gut is inhabited by a complex and metabolically active microbial ecosystem regulating host health. While many studies have focused on the effect of individual microbial taxa, the metabolic potential of the entire gut microbial ecosystem has been largely under-explored. We characterised the gut microbiome of 1,004 twins via whole shotgun metagenomic sequencing (average 39M reads per sample). We observed greater similarity, across unrelated individuals, for functional metabolic pathways (82%) than for taxonomic composition (43%). We conducted a microbiota-wide association study linking both taxonomic information and microbial metabolic pathways with 673 blood and 713 faecal metabolites (Metabolon, Inc.). Metabolic pathways associated with 34% of blood and 95% of faecal metabolites, with over 18,000 significant associations, while species-level results identified less than 3,000 associations, suggesting that coordinated action of multiple taxa is required to affect the metabolome. Finally, we estimated that the microbiome mediated a crosstalk between 71% of faecal and 15% of blood metabolites, highlighting six key species (unclassified Subdoligranulum spp., Faecalibacterium prausnitzii, Roseburia inulinivorans, Methanobrevibacter smithii, Eubacterium rectale, and Akkermansia muciniphila). Because of the large inter-person variability in microbiome composition, our results underline the importance of studying gut microbial metabolic pathways rather than focusing purely on taxonomy to find therapeutic and diagnostic targets.

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Weaning age and its effect on the development of the swine gut microbiome and resistome

10.1101/2021.05.20.444551 ◽

2021 ◽

Author(s):

Devin B Holman ◽

Katherine E Gzyl ◽

Kathy T Mou ◽

Heather K Allen

Keyword(s):

Relative Abundance ◽

Gut Microbiome ◽

Rrna Gene ◽

Metagenomic Sequencing ◽

Carbohydrate Active Enzymes ◽

Fecal Microbiome ◽

Shotgun Metagenomic Sequencing ◽

Swine Operations ◽

Weaning Age

Piglets are often weaned between 19 and 22 d of age in North America although in some swine operations this may occur at 14 d or less. Piglets are abruptly separated from their sow at weaning and are quickly transitioned from sow's milk to a plant-based diet. The effect of weaning age on the long-term development of the pig gut microbiome is largely unknown. In this study, pigs were weaned at either 14, 21, or 28 d of age and fecal samples collected 21 times from d 4 (neonatal) through to marketing at d 140. The fecal microbiome was characterized using 16S rRNA gene and shotgun metagenomic sequencing. The fecal microbiome of all piglets shifted significantly three to seven days post-weaning with an increase in microbial diversity. Several Prevotella spp. increased in relative abundance immediately after weaning as did butyrate-producing species such as Butyricicoccus porcorum, Faecalibacterium prausnitzii, and Megasphaera elsdenii. Within 7 days of weaning, the gut microbiome of pigs weaned at 21 and 28 days of age resembled that of pigs weaned at 14 d. Resistance genes to most antimicrobial classes decreased in relative abundance post-weaning with the exception of those conferring resistance to tetracyclines and macrolides-lincosamides-streptogramin B. The relative abundance of microbial carbohydrate-active enzymes (CAZymes) changed significantly in the post-weaning period with an enrichment of CAZymes involved in degradation of plant-derived polysaccharides. These results demonstrate that pigs tend to have a more similar microbiome as they age and that weaning age has only a temporary effect on the gut microbiome.

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Comparative analysis of 16S rRNA gene and metagenome sequencing in pediatric gut microbiomes

10.1101/2021.02.20.432118 ◽

2021 ◽

Author(s):

Danielle Peterson ◽

Kevin S. Bonham ◽

Sophie Rowland ◽

Cassandra W. Pattanayak ◽

Vanja Klepac-Ceraj ◽

...

Keyword(s):

16S Rrna ◽

Microbial Communities ◽

Gut Microbiome ◽

Age Groups ◽

Alpha Diversity ◽

Sequencing Depth ◽

Human Infant ◽

Rrna Gene ◽

Metagenomic Sequencing ◽

Shotgun Metagenomic Sequencing

AbstractThe colonization of the human gut microbiome begins at birth, and, over time, these microbial communities become increasingly complex. Most of what we currently know about the human microbiome, especially in early stages of development, was described using culture-independent sequencing methods that allow us to identify the taxonomic composition of microbial communities using genomic techniques, such as amplicon or shotgun metagenomic sequencing. Each method has distinct tradeoffs, but there has not been a direct comparison of the utility of these methods in stool samples from very young children, which have different features than those of adults. We compared the effects of profiling the human infant gut microbiome with 16S rRNA amplicon versus shotgun metagenomic sequencing techniques in 130 fecal samples; younger than 15, 15-30, and older than 30 months of age. We demonstrate that observed changes in alpha-diversity and beta-diversity with age occur to similar extents using both profiling methods. We also show that 16S rRNA profiling identified a larger number of genera and we find several genera that are missed or underrepresented by each profiling method. We present the link between alpha diversity and shotgun metagenomic sequencing depth for children of different ages. These findings provide a guide for selecting an appropriate method and sequencing depth for the three studied age groups.

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Yoghurt consumption is associated with transient changes in the composition of the human gut microbiome

10.21203/rs.3.rs-38248/v1 ◽

2020 ◽

Author(s):

Caroline Ivanne Le Roy ◽

Alexander Kurilshikov ◽

Emily Leeming ◽

Alessia Visconti ◽

Ruth Bowyer ◽

...

Keyword(s):

16S Rrna ◽

Gut Microbiota ◽

Visceral Fat ◽

Gut Microbiome ◽

Body Weight Gain ◽

Healthy Eating Index ◽

Rrna Gene ◽

Metagenomic Sequencing ◽

Sequencing Data ◽

Shotgun Metagenomic Sequencing

Abstract Background: Yoghurt contains live bacteria that could contribute via modulation of the gut microbiota to its reported beneficial effects such as reduced body weight gain and lower incidence of type 2 diabetes. To date, the association between yoghurt consumption and the composition of the gut microbiota is underexplored. Here we used clinical variables, metabolomics, 16S rRNA and shotgun metagenomic sequencing data collected on over 1000 predominantly female UK twins to define the link between the gut microbiota and yoghurt-associated health benefits. Results: According to food frequency questionnaires (FFQ), 73% of subjects consumed yoghurt. Consumers presented a healthier diet pattern (healthy eating index: beta = 2.17±0.34; P = 2.72x10 -10 ) and improved metabolic health characterised by reduced visceral fat (beta = -28.18±11.71 g; P = 0.01). According to 16S rRNA gene analyses and whole shotgun metagenomic sequencing approach consistent taxonomic variations were observed with yoghurt consumption. More specifically, we identified higher abundance of species used as yoghurt starters Streptococcus thermophilus (beta = 0.41±0.051; P = 6.14x10 -12 ) and sometimes added Bifidobacterium animalis subsp. lactis (beta = 0.30±0.052; P = 1.49x10 -8 ) in the gut of yoghurt consumers. Replication in 1103 volunteers from the LL-DEEP cohort confirmed the increase of S. thermophilus among yoghurt consumers. Using food records collected the day prior to faecal sampling we showed that increase in these two yoghurt bacteria could be transient. Metabolomics analysis revealed that B. animalis subsp. lactis was associated with 13 faecal metabolites including a 3-hydroxyoctanoic acid, known to be involved in the regulation of gut inflammation. Conclusions: Yoghurt consumption is associated with reduced visceral fat mass and changes in gut microbiome including transient increase of yoghurt-contained species ( i.e. S. thermophilus and B. lactis ).

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Bioavailability of a Novel Form of Microencapsulated Bovine Lactoferrin and Its Effect on Inflammatory Markers and the Gut Microbiome: A Pilot Study

Nutrients ◽

10.3390/nu10081115 ◽

2018 ◽

Vol 10 (8) ◽

pp. 1115 ◽

Cited By ~ 6

Author(s):

Clare Dix ◽

Olivia Wright

Keyword(s):

Gut Microbiome ◽

Bovine Lactoferrin ◽

Metagenomic Sequencing ◽

Serum Samples ◽

Double Blind ◽

16S Sequencing ◽

Cd8 Cells ◽

Beneficial Effects ◽

Positive Effects ◽

Before And After

Bovine lactoferrin, extracted from milk or whey, is used in a range of products to enhance immunity and support digestive health, iron absorption, and homeostasis. This study examined the absorption and effect of Progel (Brisbane, Queensland, Australia) microencapsulated bovine lactoferrin (InferrinTM, Bega Bionutrients, Victoria, Australia) on immune markers and the microbiome. A double-blind randomised, cross-over trial was conducted with 12 healthy males randomised to one of two doses, equivalent to 200 mg or 600 mg lactoferrin, for two four-week supplementation arms, with a two-week washout period. Subjects received either standard bovine lactoferrin or InferrinTM for each arm. Baseline and post each trial arm, CD69+ activation on CD4+ and CD8+ cells was analysed, bovine and human lactoferrin contents of faecal and serum samples were reported, and the gut microbiome was analysed using 16S sequencing and metagenomic sequencing. The mean level of CD69+ activation on the CD4+ cells was lower after supplementation regardless of the form or dose of lactoferrin. This was statistically significant for the 200 mg dose. A higher level of bovine lactoferrin was found post-supplementation in those taking InferrinTM, although this was not statistically significant. Changes in phylum-level microbial community profiling were detected post-supplementation in the second trial arm, particularly in those receiving InferrinTM. Metagenomic sequencing showed changes in the volumes of the top 100 species of bacteria present before and after all treatment arms. Results suggest that lactoferrin supplementation may have beneficial effects on the microbiome and immune system, and that the use of InferrinTM improves absorption. Larger detailed studies are needed to ascertain the potential positive effects of bovine lactoferrin supplementation.

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Vitamin K Antagonist Warfarin for Palliative Treatment of Metachromatic Leukodystrophy, A Compassionate Study of Four Subjects

Journal of Central Nervous System Disease ◽

10.4137/jcnsd.s9355 ◽

2012 ◽

Vol 4 ◽

pp. JCNSD.S9355 ◽

Cited By ~ 3

Author(s):

Mitra Assadi ◽

Dah-Jyuu Wang ◽

Kelly Anderson ◽

Melissa Carran ◽

Larissa Bilaniuk ◽

...

Keyword(s):

Vitamin K ◽

Metachromatic Leukodystrophy ◽

Vitamin K Antagonist ◽

Bleeding Complications ◽

Drug Trials ◽

Beneficial Effects ◽

Rats And Mice ◽

Sphingolipid Biosynthesis ◽

The Brain

MLD is characterized by accumulation of sulfatides in the brain. Vitamin K regulates two enzymes in sphingolipid biosynthesis and warfarin is known to lower brain sulfatides in rats and mice. We hypothesized that warfarin may mitigate the MLD phenotype by reducing the formation of sulfatides. This compassionate study recruited four advanced patients with clinical, biochemical and genetic confirmation of MLD. The patients were treated with warfarin according to the approved protocol for a total of 45 days. The battery of tests included proton MR spectroscopy (H-MRS) of brain and urinary sulfatide levels recorded at defined intervals. The patients tolerated the medication and there were no bleeding complications. The urinary sulfatide levels did not decline during the study period. The H-MRS showed decreased N-acetyl aspartate and elevated myoinositol levels in the basal ganglia which remained unchanged after treatment. Our study did not demonstrate any beneficial effects of warfarin in four advanced cases of MLD. The drug intervention however, was safe and deserves further evaluation through a larger study of longer duration. The metabolite abnormalities reported on H-MRS may be useful in longitudinal follow up of patients with MLD during drug trials.

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Separation of Cohorts on the Basis of Bacterial Type IV Conjugation Systems Identified From Metagenomic Assemblies

10.21203/rs.3.rs-660934/v1 ◽

2021 ◽

Author(s):

Benjamin R Joris ◽

Tyler S Browne ◽

Thomas A Hamilton ◽

David R Edgell ◽

Gregory B Gloor

Keyword(s):

North American ◽

Gut Microbiome ◽

Metagenomic Sequencing ◽

Human Gut ◽

Term Infants ◽

Human Gut Microbiome ◽

Type Iv ◽

Shotgun Metagenomic Sequencing ◽

Age Related ◽

Inflammatory Bowel

Abstract BackgroundConjugation enables the exchange of genetic elements throughout environments, including the human gut microbiome. Conjugative elements can carry and transfer clinically relevant metabolic pathways which makes precise identification of these systems in metagenomic samples clinically important. ResultsHere, we outline two distinct methods to identify conjugative elements in the human gut microbiome. We first show that conjugative elements exhibit strong population and age-level stratification. Furthermore, the taxonomic compositions of the conjugative elements differ from the composition of the metagenome assembled genomes, both in terms of the number of assembled elements and the relative abundances of the assembled systems. Finally, we demonstrate that the majority of assembled conjugative elements are not included within metagenomic bins, and that only a small proportion of the binned conjugative systems are included in "high-quality" metagenomic bins. Our findings highlight that conjugative systems differ between a North American inflammatory bowel disease cohort and a cohort of North American pre-term infants, but in a manner different than metagenome assembled genomes, revealing a potential use as an age-related biomarker. Additionally, conjugative systems can distinguish between other geographical-based cohorts. ConclusionsAnalysis of the human gut microbiome by shotgun metagenomic sequencing has revealed numerous connections to human health outcomes. Our findings emphasize the need to identify and analyze conjugative systems outside of standard metagenomic binning pipelines. We suggest that analysis of type IV conjugative systems should be added to the current metagenomic analysis approaches as they contain much information that could explain differences between cohorts beyond those we investigated.

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