Associations between untargeted plasma metabolomic signatures and gut microbiota composition in the Milieu Intérieur population of healthy adults

Abstract Host–microbial co-metabolism products are being increasingly recognised to play important roles in physiological processes. However, studies undertaking a comprehensive approach to consider host–microbial metabolic relationships remain scarce. Metabolomic analysis yielding detailed information regarding metabolites found in a given biological compartment holds promise for such an approach. This work aimed to explore the associations between host plasma metabolomic signatures and gut microbiota composition in healthy adults of the Milieu Intérieur study. For 846 subjects, gut microbiota composition was profiled through sequencing of the 16S rRNA gene in stools. Metabolomic signatures were generated through proton NMR analysis of plasma. The associations between metabolomic variables and α- and β-diversity indexes and relative taxa abundances were tested using multi-adjusted partial Spearman correlations, permutational ANOVA and multivariate associations with linear models, respectively. A multiple testing correction was applied (Benjamini–Hochberg, 10 % false discovery rate). Microbial richness was negatively associated with lipid-related signals and positively associated with amino acids, choline, creatinine, glucose and citrate (−0·133 ≤ Spearman’s ρ ≤ 0·126). Specific associations between metabolomic signals and abundances of taxa were detected (twenty-five at the genus level and nineteen at the species level): notably, numerous associations were observed for creatinine (positively associated with eleven species and negatively associated with Faecalibacterium prausnitzii). This large-scale population-based study highlights metabolites associated with gut microbial features and provides new insights into the understanding of complex host–gut microbiota metabolic relationships. In particular, our results support the implication of a ‘gut–kidney axis’. More studies providing a detailed exploration of these complex interactions and their implications for host health are needed.

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Effects of Probiotic NVP-1704 on Mental Health and Sleep in Healthy Adults: An 8-Week Randomized, Double-Blind, Placebo-Controlled Trial

Nutrients ◽

10.3390/nu13082660 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2660

Author(s):

Hyuk Joo Lee ◽

Jung Kyung Hong ◽

Jeon-Kyung Kim ◽

Dong-Hyun Kim ◽

Seok Won Jang ◽

...

Keyword(s):

Mental Health ◽

Gut Microbiota ◽

Sleep Quality ◽

Sleep Disturbances ◽

Lactobacillus Reuteri ◽

Healthy Adults ◽

Rrna Gene ◽

Microbiota Composition ◽

Bifidobacterium Adolescentis ◽

Gut Microbiota Composition

The human gut microbiome is closely linked to mental health and sleep. We aimed to verify the efficacy and safety of probiotic NVP-1704, a mixture of Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98, in improving stress, depression, anxiety, and sleep disturbances, along with the measurement of some blood biomarkers. A total of 156 healthy adults with subclinical symptoms of depression, anxiety, and insomnia were retrospectively registered and randomly assigned to receive either NVP-1704 (n = 78) or a placebo (n = 78) for eight weeks. Participants completed the Stress Response Inventory, Beck’s Depression and Anxiety Inventory, Pittsburg Sleep Quality Index, and Insomnia Severity Index at baseline, at four and eight weeks of treatment. Pre- and post-treatment blood tests for biomarkers were conducted. After intervention, gut microbiota composition was quantified by pyrosequencing the bacterial 16S rRNA gene. The NVP-1704 group had a more significant reduction in depressive symptoms at four and eight weeks of treatment, and anxiety symptoms at four weeks compared to the placebo group. Those receiving NVP-1704 also experienced an improvement in sleep quality. NVP-1704 treatment led to a decrease in serum interleukin-6 levels. Furthermore, NVP-1704 increased Bifidobacteriaceae and Lactobacillacea, whereas it decreased Enterobacteriaceae in the gut microbiota composition. Our findings suggest that probiotic NVP-1704 could be beneficial for mental health and sleep.

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Investigating the Gut Microbiota Composition of Individuals with Attention-Deficit/Hyperactivity Disorder and Association with Symptoms

10.20944/preprints202002.0082.v1 ◽

2020 ◽

Author(s):

Joanna Szopinska-Tokov ◽

Sarita Dam ◽

Jilly Naaijen ◽

Prokopis Konstanti ◽

Nanda Rommelse ◽

...

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Gut Microbiota ◽

Attention Deficit ◽

Multiple Testing ◽

Neurodevelopmental Disorder ◽

Microbiota Composition ◽

Multiple Testing Correction ◽

Hyperactivity Disorder ◽

Gut Microbiota Composition

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Given the growing evidence of gut microbiota being involved in psychiatric (including neurodevelopmental) disorders, we aimed to identify differences in gut microbiota composition between participants with ADHD and controls and to investigate the role of the microbiota in inattention and hyperactivity/impulsivity. Fecal samples were collected from 107 participants (NADHD=42; Ncontrols=50; NsubthreholdADHD=15; range age: 13-29 years). The relative quantification of bacterial taxa was done using 16S ribosomal RNA gene amplicon sequencing. Beta-diversity revealed significant differences in bacterial composition between participants with ADHD and healthy controls, which was also significant for inattention, but showing a trend in case of hyperactivity/impulsivity only. Ten genera showed nominal differences (P < 0.05) between both groups, of which seven genera were tested for their association with ADHD symptom scores (adjusting for age, sex, body mass index, time delay between feces collection and symptoms assessment, medication use and family relatedness). Our results show that variation of a genus from the Ruminococcaceae family (Ruminococcaceae_UCG_004) is associated (after multiple testing correction) with inattention symptoms, and suggest a role of gut microbiota in ADHD pathophysiology.

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Investigating the Gut Microbiota Composition of Individuals with Attention-Deficit/Hyperactivity Disorder and Association with Symptoms

Microorganisms ◽

10.3390/microorganisms8030406 ◽

2020 ◽

Vol 8 (3) ◽

pp. 406 ◽

Cited By ~ 6

Author(s):

Joanna Szopinska-Tokov ◽

Sarita Dam ◽

Jilly Naaijen ◽

Prokopis Konstanti ◽

Nanda Rommelse ◽

...

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Gut Microbiota ◽

Attention Deficit ◽

Multiple Testing ◽

Neurodevelopmental Disorder ◽

Microbiota Composition ◽

Multiple Testing Correction ◽

Hyperactivity Disorder ◽

Gut Microbiota Composition

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Given the growing evidence of gut microbiota being involved in psychiatric (including neurodevelopmental) disorders, we aimed to identify differences in gut microbiota composition between participants with ADHD and controls and to investigate the role of the microbiota in inattention and hyperactivity/impulsivity. Fecal samples were collected from 107 participants (NADHD = 42; Ncontrols = 50; NsubthreholdADHD = 15; range age: 13–29 years). The relative quantification of bacterial taxa was done using 16S ribosomal RNA gene amplicon sequencing. Beta-diversity revealed significant differences in bacterial composition between participants with ADHD and healthy controls, which was also significant for inattention, but showing a trend in case of hyperactivity/impulsivity only. Ten genera showed nominal differences (p < 0.05) between both groups, of which seven genera were tested for their association with ADHD symptom scores (adjusting for age, sex, body mass index, time delay between feces collection and symptoms assessment, medication use, and family relatedness). Our results show that variation of a genus from the Ruminococcaceae family (Ruminococcaceae_UCG_004) is associated (after multiple testing correction) with inattention symptoms and support the potential role of gut microbiota in ADHD pathophysiology.

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Colonisation potential of plantaricin-producing Lactobacillus plantarum SF9C andS-layer-carrying Lactobacillus brevis SF9B among gut microbiota

10.21203/rs.2.23400/v2 ◽

2020 ◽

Author(s):

Katarina Butorac ◽

Martina Banic ◽

Jasna Novak ◽

Andreja Leboš Pavunc ◽

Ksenija Uroic ◽

...

Keyword(s):

Gut Microbiota ◽

Lactobacillus Plantarum ◽

Lactobacillus Brevis ◽

Illumina Miseq ◽

Rrna Gene ◽

Microbiota Composition ◽

Combined Application ◽

Probiotic Potential ◽

Gut Microbiota Composition

Abstract Background: The influence of an S-layer-carrying strain Lactobacillus brevis SF9B and a plantaricin-producing strain Lactobacillus plantarum SF9C on the gut microbiota composition was evaluated in the rats. Considering the probiotic potential of Lb. brevis SF9B, this study aimed to examine the antibacterial activity of Lb. plantarum SF9C and potential for their in vivo colonisation, which could be the basis for the investigation of their synergistic functionality. Results: A plantaricin-encoding cluster was identified in Lb. plantarum SF9C, a strain which efficiently inhibited the growth of Listeria monocytogenes ATCC®19111™ and Staphylococcus aureus 3048. Contrary to the plantaricin-producing SF9C strain, the S-layer-carrying SF9B strain excluded Escherichia coli 3014 and Salmonella enterica serovar Typhimurium FP1 from adhesion to Caco-2 cells. Finally, DGGE analysis of the V2-V3 region of the 16S rRNA gene confirmed the transit of two selected lactobacilli through the gastrointestinal tract (GIT). Microbiome profiling via the Illumina MiSeq platform revealed the prevalence of Lactobacillus spp. in the gut microbiota of rats suggesting their colonisation potential in GIT.Conclusion: The combined application of Lb. plantarum SF9C and Lb. brevis SF9B could influence the intestinal microbiota composition, which is reflected through the increased abundance of Lactobacillus genus, but also through altered abundances of other bacterial genera, either in the model of healthy or aberrant microbiota of rats. The obtained results contributed to the functional aspects of SF9C and SF9B strains which could be incorporated in the probiotic-containing functional foods and therefore have a beneficial influence on the gut microbiota composition.

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Ontogenetic Differences in Dietary Fat Influence Microbiota Assembly in the Zebrafish Gut

mBio ◽

10.1128/mbio.00687-15 ◽

2015 ◽

Vol 6 (5) ◽

Cited By ~ 50

Author(s):

Sandi Wong ◽

W. Zac Stephens ◽

Adam R. Burns ◽

Keaton Stagaman ◽

Lawrence A. David ◽

...

Keyword(s):

Gut Microbiota ◽

Microbial Communities ◽

Dietary Fat ◽

Rrna Gene ◽

Microbiota Composition ◽

Ideal Model ◽

Surrounding Environment ◽

Animal Hosts ◽

The Relationship ◽

Gut Microbiota Composition

ABSTRACT Gut microbiota influence the development and physiology of their animal hosts, and these effects are determined in part by the composition of these microbial communities. Gut microbiota composition can be affected by introduction of microbes from the environment, changes in the gut habitat during development, and acute dietary alterations. However, little is known about the relationship between gut and environmental microbiotas or about how host development and dietary differences during development impact the assembly of gut microbiota. We sought to explore these relationships using zebrafish, an ideal model because they are constantly immersed in a defined environment and can be fed the same diet for their entire lives. We conducted a cross-sectional study in zebrafish raised on a high-fat, control, or low-fat diet and used bacterial 16S rRNA gene sequencing to survey microbial communities in the gut and external environment at different developmental ages. Gut and environmental microbiota compositions rapidly diverged following the initiation of feeding and became increasingly different as zebrafish grew under conditions of a constant diet. Different dietary fat levels were associated with distinct gut microbiota compositions at different ages. In addition to alterations in individual bacterial taxa, we identified putative assemblages of bacterial lineages that covaried in abundance as a function of age, diet, and location. These results reveal dynamic relationships between dietary fat levels and the microbial communities residing in the intestine and the surrounding environment during ontogenesis. IMPORTANCE The ability of gut microbiota to influence host health is determined in part by their composition. However, little is known about the relationship between gut and environmental microbiotas or about how ontogenetic differences in dietary fat impact gut microbiota composition. We addressed these gaps in knowledge using zebrafish, an ideal model organism because their environment can be thoroughly sampled and they can be fed the same diet for their entire lives. We found that microbial communities in the gut changed as zebrafish aged under conditions of a constant diet and became increasingly different from microbial communities in their surrounding environment. Further, we observed that the amount of fat in the diet had distinct age-specific effects on gut community assembly. These results reveal the complex relationships between microbial communities residing in the intestine and those in the surrounding environment and show that these relationships are shaped by dietary fat throughout the life of animal hosts.

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IgA-deficient humans exhibit gut microbiota dysbiosis despite secretion of compensatory IgM

Scientific Reports ◽

10.1038/s41598-019-49923-2 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 24

Author(s):

Jason R. Catanzaro ◽

Juliet D. Strauss ◽

Agata Bielecka ◽

Anthony F. Porto ◽

Francis M. Lobo ◽

...

Keyword(s):

Gut Microbiota ◽

16S Rrna Gene Sequencing ◽

Iga Deficiency ◽

Secretory Iga ◽

Rrna Gene ◽

Healthy Controls ◽

Microbiota Composition ◽

Antibody Isotype ◽

Selective Iga Deficiency ◽

Gut Microbiota Composition

Abstract Immunoglobulin A is the dominant antibody isotype found in mucosal secretions and enforces host-microbiota symbiosis in mice, yet selective IgA-deficiency (sIgAd) in humans is often described as asymptomatic. Here, we determined the effects of IgA deficiency on human gut microbiota composition and evaluated the possibility that mucosal secretion of IgM can compensate for a lack of secretory IgA. We used 16S rRNA gene sequencing and bacterial cell sorting to evaluate gut microbiota composition and taxa-specific antibody coating of the gut microbiota in 15 sIgAd subjects and matched controls. Despite the secretion of compensatory IgM into the gut lumen, sIgAd subjects displayed an altered gut microbiota composition as compared to healthy controls. These alterations were characterized by a trend towards decreased overall microbial diversity as well as significant shifts in the relative abundances of specific microbial taxa. While secretory IgA in healthy controls targeted a defined subset of the microbiota via high-level coating, compensatory IgM in sIgAd subjects showed less specificity than IgA and bound a broader subset of the microbiota. We conclude that IgA plays a critical and non-redundant role in controlling gut microbiota composition in humans and that secretory IgA has evolved to maintain a diverse and stable gut microbial community.

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The microbiota of farmed mink (Neovison vison) follows a successional development and is affected by early life antibiotic exposure

Scientific Reports ◽

10.1038/s41598-020-77417-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Martin Iain Bahl ◽

Anabelle Legarth Honoré ◽

Sanne Tygesen Skønager ◽

Oliver Legarth Honoré ◽

Tove Clausen ◽

...

Keyword(s):

Gut Microbiota ◽

Early Life ◽

Intramuscular Administration ◽

Control Group ◽

Rrna Gene ◽

Antibiotic Administration ◽

Lactation Period ◽

Microbiota Composition ◽

Gut Microbiota Composition ◽

Successional Development

AbstractOn many mink farms, antibiotics are used extensively during the lactation period to reduce the prevalence and severity of pre-weaning diarrhoea (PWD) in mink kits (also referred to as greasy kit syndrome). Concerns have been raised, that routine treatment of PWD with antibiotics could affect the natural successional development of the gut microbiota, which may have long lasting consequences. Here we investigated the effects of early life antibiotic treatment administered for 1 week (postnatal days 13–20). Two routes of antibiotic administration were compared to a non-treated control group (CTR, n = 24). Routes of administration included indirect treatment, through the milk from dams receiving antibiotics by intramuscular administration (ABX_D, n = 24) and direct treatment by intramuscular administration to the kits (ABX_K, n = 24). A tendency for slightly increased weight at termination (Day 205) was observed in the ABX_K group. The gut microbiota composition was profiled by 16S rRNA gene sequencing at eight time points between Day 7 and Day 205. A clear successional development of the gut microbiota composition was observed and both treatment regimens caused detectable changes in the gut microbiota until at least eight days after treatment ceased. At termination, a significant positive correlation was identified between microbial diversity and animal weight.

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Osteopontin-Enriched Algae Modulates the Gut Microbiota Composition in Weaning Piglets Infected with Enterotoxigenic Escherichia Coli (P06-069-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz031.p06-069-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Cited By ~ 1

Author(s):

Mei Wang ◽

Brooke Smith ◽

Brock Adams ◽

Miller Tran ◽

Ryan Dilger ◽

...

Keyword(s):

Escherichia Coli ◽

Gut Microbiota ◽

Alpha Diversity ◽

Enterotoxigenic Escherichia Coli ◽

Farm Animals ◽

Future Research ◽

Rrna Gene ◽

Microbiota Composition ◽

Wild Type ◽

Gut Microbiota Composition

Abstract Objectives Enterotoxigenic Escherichia coli (ETEC) are an important cause of diarrhea in human infants and young farm animals. Osteopontin (OPN), a glycoprotein present in high concentration in human milk, has immunomodulatory functions, which could indirectly impact the microbiota. Furthermore, a previous study has shown fecal microbiota composition differs between wild-type and OPN knockout mice. Herein, the effects of OPN-enriched algae on the gut microbiota composition and volatile fatty acid (VFA) concentrations of ETEC-infected piglets were assessed. Methods Naturally-farrowed piglets were sow-reared for 21 days and then randomized to two weaning diets: WT (formula + 1% wild-type algae) or OPN (formula + 1% OPN-enriched algae). On postnatal day (PND) 31, all piglets were infected orally with a live culture of ETEC (1010 colony-forming unit/3 mL dose) daily for three consecutive days. On PND 41, ascending colon (AC) contents were collected. Gut microbiota was assessed by sequencing V3-V4 regions of 16S rRNA gene and VFAs were determined by gas chromatography. Alpha-diversity and VFAs were analyzed using PROC MIXED procedure of SAS. Beta-diversity was evaluated by permutational multivariate analysis of variance (PERMANOVA) and differential abundance analysis on the bacterial genera was performed using DESeq2 package of R. Results Shannon indices were lower in the AC contents of OPN piglets compared to WT piglets. The overall colonic microbiota of OPN piglets differed from that of WT piglets (PERMANOVA P = 0.015). At genus level, OPN-enriched algae increased the abundance of Streptococcus, decreased the abundances of Sutterella, Candidatus Soleaferrea, dga-11 gut group, Rikenellaceae RC9 gut group, Ruminococcaceae UCG-010, unculturedRuminococcaceae, Prevotella 2 and 7 compared to piglets consuming wild-type algae (P < 0. 05). OPN piglets also had higher (P < 0.05) concentrations of acetate, propionate, butyrate and valerate compared to WT. Conclusions In ETEC infected piglets, 1% OPN-enriched algae decreased alpha-diversity and modulated the microbiota composition and VFA profiles compared to 1% WT algae. Other studies have shown that OPN inhibits biofilm formation in vitro, but future research is needed to assess in vivo microbiome-modulation mechanisms. Funding Sources Triton Algae Innovations.

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Gut microbiota composition in relation to intake of added sugar, sugar-sweetened beverages and artificially sweetened beverages in the Malmö Offspring Study

European Journal of Nutrition ◽

10.1007/s00394-020-02392-0 ◽

2020 ◽

Author(s):

Stina Ramne ◽

Louise Brunkwall ◽

Ulrika Ericson ◽

Nicola Gray ◽

Gunter G. C. Kuhnle ◽

...

Keyword(s):

Gut Microbiota ◽

Negative Binomial ◽

Metagenomic Sequencing ◽

Microbiota Composition ◽

Multiple Testing Correction ◽

Sugar Sweetened Beverages ◽

Added Sugar ◽

Sweetened Beverages ◽

Gut Microbiota Composition ◽

Artificially Sweetened Beverages

Abstract Purpose It has been suggested that a high intake of sugar or sweeteners may result in an unfavorable microbiota composition; however, evidence is lacking. Hence, in this exploratory epidemiological study, we aim to examine if intake of added sugar, sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) associate with the gut microbiota composition. Methods Participants (18–70 years) in the Malmö Offspring Study have provided blood, urine, and fecal samples and completed both web-based 4 day food records and short food frequency questionnaires. The gut microbiota was assessed by 16S rRNA sequencing, processed in QIIME and matched to Greengenes (v.13.8), giving 64 included genera after filtering. Intake of added sugar (n = 1371) (also supported by the overnight urinary sugar biomarker in a subgroup n = 577), SSBs (n = 1086) and ASBs (n = 1085) were examined as exposures in negative binomial regressions. Results Various genera nominally associated with intake of added sugar, SSBs, and ASBs. Only the negative association between SSB intake and Lachnobacterium remained significant after multiple testing correction. A positive association between SSB intake and the Firmicutes:Bacteroidetes ratio was also observed. Conclusion In this wide population, the cross-sectional associations between added sugar and sweet beverage intake and the gut microbiota are modest, but the results suggest that SSB intake is associated negatively with the genus Lachnobacterium and positively with the Firmicutes:Bacteroidetes ratio. Larger studies, preferably using metagenomic sequencing, are needed to further evaluate if a link exists between intake of sugars and sweeteners and the human gut microbiota.

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