A gut commensal niche regulates stable association of a multispecies microbiota

AbstractThe intestines of animals are typically colonized by a complex, relatively stable microbiota that influences health and fitness, but the underlying mechanisms of colonization remain poorly understood. As a typical animal, the fruit fly, Drosophila melanogaster, is associated with a consistent set of commensal bacterial species, yet the reason for this consistency is unknown. Here, we use gnotobiotic flies, microscopy, and microbial pulse-chase protocols to show that a commensal niche exists within the proventriculus region of the Drosophila foregut that selectively binds bacteria with exquisite strain-level specificity. Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus physically remodels the niche to favor secondary colonization by Acetobacter. Our results provide a mechanistic framework for understanding the establishment and stability of an intestinal microbiome.One-Sentence SummaryA strain-specific set of bacteria inhabits a defined spatial region of the Drosophila gut that forms a commensal niche.

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Discovery of novel community-relevant small proteins in a simplified human intestinal microbiome

Microbiome ◽

10.1186/s40168-020-00981-z ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Hannes Petruschke ◽

Christian Schori ◽

Sebastian Canzler ◽

Sarah Riesbeck ◽

Anja Poehlein ◽

...

Keyword(s):

Microbial Communities ◽

Intestinal Microbiota ◽

De Novo ◽

Bacterial Species ◽

Intestinal Microbiome ◽

Single Strain ◽

Small Proteins ◽

Human Intestinal Microbiota ◽

Wide Range

Abstract Background The intestinal microbiota plays a crucial role in protecting the host from pathogenic microbes, modulating immunity and regulating metabolic processes. We studied the simplified human intestinal microbiota (SIHUMIx) consisting of eight bacterial species with a particular focus on the discovery of novel small proteins with less than 100 amino acids (= sProteins), some of which may contribute to shape the simplified human intestinal microbiota. Although sProteins carry out a wide range of important functions, they are still often missed in genome annotations, and little is known about their structure and function in individual microbes and especially in microbial communities. Results We created a multi-species integrated proteogenomics search database (iPtgxDB) to enable a comprehensive identification of novel sProteins. Six of the eight SIHUMIx species, for which no complete genomes were available, were sequenced and de novo assembled. Several proteomics approaches including two earlier optimized sProtein enrichment strategies were applied to specifically increase the chances for novel sProtein discovery. The search of tandem mass spectrometry (MS/MS) data against the multi-species iPtgxDB enabled the identification of 31 novel sProteins, of which the expression of 30 was supported by metatranscriptomics data. Using synthetic peptides, we were able to validate the expression of 25 novel sProteins. The comparison of sProtein expression in each single strain versus a multi-species community cultivation showed that six of these sProteins were only identified in the SIHUMIx community indicating a potentially important role of sProteins in the organization of microbial communities. Two of these novel sProteins have a potential antimicrobial function. Metabolic modelling revealed that a third sProtein is located in a genomic region encoding several enzymes relevant for the community metabolism within SIHUMIx. Conclusions We outline an integrated experimental and bioinformatics workflow for the discovery of novel sProteins in a simplified intestinal model system that can be generically applied to other microbial communities. The further analysis of novel sProteins uniquely expressed in the SIHUMIx multi-species community is expected to enable new insights into the role of sProteins on the functionality of bacterial communities such as those of the human intestinal tract.

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Social modulation of oogenesis and egg-laying in Drosophila melanogaster

10.1101/2021.09.13.460109 ◽

2021 ◽

Author(s):

Bailly Tiphaine ◽

Philip Kohlmeier ◽

Rampal Etienne ◽

Bregje Wertheim ◽

Jean-Christophe Billeter

Keyword(s):

Drosophila Melanogaster ◽

Social Context ◽

Social Systems ◽

Fruit Fly ◽

Egg Laying ◽

Physiological Adaptation ◽

Group Members ◽

Selection For ◽

Underlying Mechanisms ◽

Gravid Females

Being part of a group facilitates cooperation between group members, but also creates competition for limited resources. This conundrum is problematic for gravid females who benefit from being in a group, but whose future offspring may struggle for access to nutrition in larger groups. Females should thus modulate their reproductive output depending on their social context. Although social-context dependent modulation of reproduction is documented in a broad range of species, its underlying mechanisms and functions are poorly understood. In the fruit fly Drosophila melanogaster, females actively attract conspecifics to lay eggs on the same resources, generating groups in which individuals may cooperate or compete. The tractability of the genetics of this species allows dissecting the mechanisms underlying physiological adaptation to their social context. Here, we show that females produce eggs increasingly faster as group size increases. By laying eggs faster in group than alone, females appear to reduce competition between offspring and increase their likelihood of survival. In addition, females in a group lay their eggs during the light phase of the day, while isolated females lay them during the night. We show that responses to the presence of others are determined by vision through the motion detection pathway and that flies from any sex, mating status or species can trigger these responses. The mechanisms of this modulation of egg-laying by group is connected to a lifting of the inhibition of light on oogenesis and egg-laying by stimulating hormonal pathways involving juvenile hormone. Because modulation of reproduction by social context is a hallmark of animals with higher levels of sociality, our findings represent a protosocial mechanism in a species considered solitary that may have been the target of selection for the evolution of more complex social systems.

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Effects of Lactobacillus plantarum Q180 on Postprandial Lipid Levels and Intestinal Environment: A Double-Blind, Randomized, Placebo-Controlled, Parallel Trial

Nutrients ◽

10.3390/nu12010255 ◽

2020 ◽

Vol 12 (1) ◽

pp. 255 ◽

Cited By ~ 1

Author(s):

Ye Eun Park ◽

Min Seo Kim ◽

Kyung Won Shim ◽

You-Il Kim ◽

Jaeryang Chu ◽

...

Keyword(s):

Lactobacillus Plantarum ◽

Intestinal Microbiome ◽

Controlled Study ◽

Lipid Levels ◽

Double Blind ◽

Apo B ◽

Intestinal Environment ◽

Postprandial Lipid Metabolism ◽

Postprandial Lipid ◽

Underlying Mechanisms

Probiotics can improve the intestinal environment by enhancing beneficial bacteria to potentially regulate lipid levels; however, the underlying mechanisms remain unclear. The aim of this study was to investigate the effect of Lactobacillus plantarum Q180 (LPQ180) on postprandial lipid metabolism and the intestinal microbiome environment from a clinical perspective. A double-blind, randomized, placebo-controlled study was conducted including 70 participants of both sexes, 20 years of age and older, with healthy blood triacylglyceride (TG) levels below 200 mg/dL. Treatment with LPQ180 for 12 weeks significantly decreased LDL-cholesterol (p = 0.042) and apolipoprotein (Apo)B-100 (p = 0.003) levels, and decreased postprandial maximum concentrations (Cmax) and areas under the curve (AUC) of TG, chylomicron TG, ApoB-48, and ApoB-100. LPQ180 treatment significantly decreased total indole and phenol levels (p = 0.019). In addition, there was a negative correlation between baseline microbiota abundance and lipid marker change, which was negatively correlated with metabolites. This study suggests that LPQ180 might be developed as a functional ingredient to help maintain healthy postprandial lipid levels through modulating gut environment.

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A high-resolution pipeline for 16S-sequencing identifies bacterial strains in human microbiome

10.1101/565572 ◽

2019 ◽

Cited By ~ 1

Author(s):

Igor Segota ◽

Tao Long

Keyword(s):

Bacterial Species ◽

Human Microbiome ◽

Amplicon Sequencing ◽

R Package ◽

Strain Level ◽

Sequencing Data ◽

Bacterial Strains ◽

16S Sequencing ◽

16S Amplicon Sequencing ◽

Sequencing Data Analysis

We developed a High-resolution Microbial Analysis Pipeline (HiMAP) for 16S amplicon sequencing data analysis, aiming at bacterial species or strain-level identification from human microbiome to enable experimental validation for causal effects of the associated bacterial strains on health and diseases. HiMAP achieved higher accuracy in identifying species in human microbiome mock community than other pipelines. HiMAP identified majority of the species, with strain-level resolution wherever possible, as detected by whole genome shotgun sequencing using MetaPhlAn2 and reported comparable relative abundances. HiMAP is an open-source R package available at https://github.com/taolonglab/himap.

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Finally, Bulk Typing of Bacterial Species down to Strain Level using ON-rep-seq

10.1101/402156 ◽

2018 ◽

Author(s):

Łukasz Krych ◽

Josué L. Castro-Mejía ◽

Daniel N. Moesby ◽

Morten B. Mikkelsen ◽

Morten A. Rasmussen ◽

...

Keyword(s):

High Speed ◽

Bacterial Species ◽

Cost Effective ◽

Species Level ◽

Strain Level ◽

Read Length ◽

High Quality ◽

Sequencing Platform ◽

Culture Independent ◽

Single Flow

AbstractDespite the massive developments within culture-independent methods for detection and quantification of microorganisms during the last decade, culture-based methods remain a cornerstone in microbiology. We have developed a new method for bacterial DNA enrichment and tagmentation allowing fast (< 24h) and cost-effective species level identification and strain level differentiation using the MinION portable sequencing platform (ON-rep-seq). DNA library preparation takes less than 5h and ensures highly reproducible distribution of reads that can be used to generate strain level specific read length counts profiles (LCp). We have developed a pipeline that by correcting the random error of reads within peaks of LCp generates a set (∼10 contigs per sample; 300bp - 3Kb) of high quality (>99%) consensus reads. Whereas, the information from high quality reads is used to retrieve species level taxonomy, comparison of LCp allows for strain level differentiation. With benchmarked 288 isolates identified on a single flow cell and a theoretical throughput to evaluate over 1000 isolates, our method allows for detailed bacterial identification for less than 2$ per sample at very high speed.

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Switching on the light: using metagenomic shotgun sequencing to characterize the intestinal microbiome of Atlantic cod

10.1101/545889 ◽

2019 ◽

Author(s):

Even Sannes Riiser ◽

Thomas H.A. Haverkamp ◽

Srinidhi Varadharajan ◽

Ørnulf Borgan ◽

Kjetill S. Jakobsen ◽

...

Keyword(s):

Gadus Morhua ◽

Atlantic Cod ◽

North Atlantic Ocean ◽

Bacterial Species ◽

Abundant Species ◽

Shotgun Sequencing ◽

Intestinal Microbiome ◽

Geographical Differences ◽

Important Species ◽

The North

AbstractThe biological roles of the intestinal microbiome and how it is impacted by environmental factors are yet to be determined in wild marine fish species. Atlantic cod (Gadus morhua) is an ecologically important species with a wide-spread distribution in the North Atlantic Ocean. 16S rRNA-based amplicon analyses found no geographical differentiation between the intestinal microbiome of Atlantic cod from different locations. Nevertheless, it is unclear if this lack of differentiation results from an insufficient resolution of this method to resolve fine-scaled biological complexity. Here, we take advantage of the increased resolution provided by metagenomic shotgun sequencing to investigate the intestinal microbiome of 19 adult Atlantic cod individuals from two coastal populations in Norway – located 470 km apart. Our results show that the intestinal microbiome is dominated by theVibrionalesorder, consisting of varying abundances ofPhotobacterium, AliivibrioandVibriospecies. Moreover, resolving the species community to unprecedented resolution, we identify two abundant species,P. iliopiscariumandP. kishitanii,which comprise over 50% of the classified reads. Interestingly, genomic data shows that the intestinalP. kishitaniistrains have functionally intactluxgenes, and its high abundance suggests that fish intestines form an important part of its ecological niche. These observations support a hypothesis that bioluminescence plays an ecological role in the marine food web. Despite our improved taxonomical resolution, we identify no geographical differences in bacterial community structure, indicating that the intestinal microbiome of these coastal cod is colonized by a limited number of closely related bacterial species with a broad geographical distribution that are well suited to thrive in this host-associated environment.

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Feeding a Low-protein Maternal Diet Affects Qinghai Bamei Piglet Jejunal Microbiome-metabolome Response

10.21203/rs.3.rs-591216/v1 ◽

2021 ◽

Author(s):

Jipeng Jin ◽

Liping Zhang ◽

Qian Chen ◽

Cunming Ma ◽

Jianlei Jia ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Bacterial Species ◽

Relative Weight ◽

Integrated Approach ◽

Intestinal Microbiome ◽

Rrna Gene ◽

Metabolic Profiles ◽

Microbial Composition ◽

Suckling Piglets

Abstract This experiment investigated the impacts of feeding a maternal low-CP concentration diet having iso-essential amino acids on new born suckling piglets intestinal microbial composition and metabolic profiles. The Bamei swine breed was selected due to high meat quality and flavor, but demonstrates slower growth rates which may be related to jejunal nutrient supply. Forty randomly selected purebred Bamei sows were divided into two groups and fed a low dietary CP (12%, LP) or a normal CP (14%, CON) diet, respectively, but formulated to contain similar (iso-) essential amino acid concentrations per current recommendations. At 21 days, 12 piglets were randomly selected from each treatment and euthanized with jejunum content samples collected. The 16S rRNA gene sequencing and mass spectrometry-based metabolomics profiling were combined as an integrated approach for evaluating the functional impact of maternal CP concentrations on piglet intestinal microbiome. Even though piglets demonstrated similar 0 to 21 d ADG among treatments, the jejunum relative weight, villus width, crypt depth and muscular thickness were increased (P < 0.05), while villus height, and villus height:crypt depth were reduced (P < 0.05) for the material LP compared to the maternal fed CON diet. Maternal CP concentrations can modify the intestinal microbial composition of Bamei suckling piglets. The relative abundances of the bacterial species Escherichia-Shigella, Actinobacillus, Clostridium_sensu_stricto_1, Veillonella, and Turicibacter were increased (P < 0.05) in the maternal LP fed diet compared with the maternal fed CON diet. Jejunal digesta metabolomics analysis indicated that several amino acids were metabolized (i.e. cys, met, tyr phe and trp), biosynthesized (arg phe, tyr, and trp), or degraded (lys) were enriched (P < 0.05) for the maternal fed LP compared with the maternal fed CON. Correlation analysis demonstrated that certain intestinal bacterial genera were highly related to the histomorphology and altered intestinal microbiota metabolites. In conclusion, maternal dietary CP concentrations in excess of protein and amino acid requirements not only altered suckling Bamei piglets histomorphology, microbial composition and function, but also modulated jejunum microbial metabolic profiles, which aids in understanding the beneficial effects when feeding a maternal LP diet on piglet intestinal health.

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Stable association of a Drosophila-derived microbiota with its animal partner and the nutritional environment upon transfer between populations and generations

10.1101/111492 ◽

2017 ◽

Cited By ~ 1

Author(s):

Mélisandre A. Téfit ◽

Benjamin Gillet ◽

Pauline Joncour ◽

Sandrine Hughes ◽

François Leulier

Keyword(s):

Bacterial Communities ◽

Fruit Fly ◽

The Past ◽

Nutritional Environment ◽

Stable Association ◽

Feeding Substrate ◽

The One ◽

Reciprocal Transfer ◽

The Relationship

AbstractIn the past years, the fruit fly Drosophila melanogaster has been extensively used to study the relationship between animals and their associated microbes. Compared to the one of wild populations, the microbiota of laboratory-reared flies is less diverse, and comprises fewer bacterial taxa; nevertheless, the main commensal bacteria found in fly microbiota always belong to the Acetobacteraceae and Lactobacillaceae families. The bacterial communities associated with the fly are environmentally acquired, and the partners engage in a perpetual re-association process. Adult flies constantly ingest and excrete microbes from and onto their feeding substrate, which are then transmitted to the next generation developing within this shared habitat. We wanted to analyze the potential changes in the bacterial community during its reciprocal transfer between the two compartments of the niche (i.e. the fly and the diet). To address this question, we used a diverse, wild-derived microbial community and analyzed its relationship with the fly population and the nutritive substrate in a given habitat. Here we show that the community was overall well maintained upon transmission to a new niche, to a new fly population and to their progeny, illustrating the stable association of a Drosophila-derived microbiota with its fly partner and the nutritional environment. These results highlight the preponderant role of the nutritional substrate in the dynamics of Drosophila/microbiota interactions, and the need to fully integrate this variable when performing such studies.

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Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy

Science ◽

10.1126/science.abc3421 ◽

2020 ◽

Vol 369 (6510) ◽

pp. 1481-1489 ◽

Cited By ~ 24

Author(s):

Lukas F. Mager ◽

Regula Burkhard ◽

Nicola Pett ◽

Noah C. A. Cooke ◽

Kirsty Brown ◽

...

Keyword(s):

Antitumor Immunity ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Bacterial Species ◽

Intestinal Bacteria ◽

Gut Barrier Function ◽

Mouse Models Of Cancer ◽

Underlying Mechanisms ◽

Immune Pathway ◽

Cell Expression

Several species of intestinal bacteria have been associated with enhanced efficacy of checkpoint blockade immunotherapy, but the underlying mechanisms by which the microbiome enhances antitumor immunity are unclear. In this study, we isolated three bacterial species—Bifidobacterium pseudolongum, Lactobacillus johnsonii, and Olsenella species—that significantly enhanced efficacy of immune checkpoint inhibitors in four mouse models of cancer. We found that intestinal B. pseudolongum modulated enhanced immunotherapy response through production of the metabolite inosine. Decreased gut barrier function induced by immunotherapy increased systemic translocation of inosine and activated antitumor T cells. The effect of inosine was dependent on T cell expression of the adenosine A2A receptor and required costimulation. Collectively, our study identifies a previously unknown microbial metabolite immune pathway activated by immunotherapy that may be exploited to develop microbial-based adjuvant therapies.

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The Gut Barrier, Intestinal Microbiota, and Liver Disease: Molecular Mechanisms and Strategies to Manage

International Journal of Molecular Sciences ◽

10.3390/ijms21218351 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8351

Author(s):

Julio Plaza-Díaz ◽

Patricio Solís-Urra ◽

Fernando Rodríguez-Rodríguez ◽

Jorge Olivares-Arancibia ◽

Miguel Navarro-Oliveros ◽

...

Keyword(s):

Liver Disease ◽

Intestinal Microbiota ◽

Animal Studies ◽

Molecular Mechanisms ◽

Bacterial Species ◽

Intestinal Barrier ◽

Lifestyle Changes ◽

Alcoholic Fatty Liver ◽

Underlying Mechanisms

Liver disease encompasses pathologies as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, alcohol liver disease, hepatocellular carcinoma, viral hepatitis, and autoimmune hepatitis. Nowadays, underlying mechanisms associating gut permeability and liver disease development are not well understood, although evidence points to the involvement of intestinal microbiota and their metabolites. Animal studies have shown alterations in Toll-like receptor signaling related to the leaky gut syndrome by the action of bacterial lipopolysaccharide. In humans, modifications of the intestinal microbiota in intestinal permeability have also been related to liver disease. Some of these changes were observed in bacterial species belonging Roseburia, Streptococcus, and Rothia. Currently, numerous strategies to treat liver disease are being assessed. This review summarizes and discusses studies addressed to determine mechanisms associated with the microbiota able to alter the intestinal barrier complementing the progress and advancement of liver disease, as well as the main strategies under development to manage these pathologies. We highlight those approaches that have shown improvement in intestinal microbiota and barrier function, namely lifestyle changes (diet and physical activity) and probiotics intervention. Nevertheless, knowledge about how such modifications are beneficial is still limited and specific mechanisms involved are not clear. Thus, further in-vitro, animal, and human studies are needed.

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