Johan van Hylckama Vlieg

Chr. Hansen A/S · Human Health and Microbiome Innovation

Synthetic glycans (SGs) containing glycosidic linkages and structures not identified in nature offer a means for deliberately altering microbial community properties. Here pools of SG oligosaccharides were generated via polymerization of monosaccharides and screened for their ability to increase saccharolytic Bacteroides in ex vivo cultures of huma...

Study question Investigate the safety of VMT and explore its effects on the vaginal microbiomes and local inflammation in healthy, asymptomatic volunteer women screened for vaginal dysbiosis Summary answer We demonstrate safety and engraftment of donor bacteria in 50% of recipients, and a distinct shift in local inflammatory markers following reso...

Here we describe the first double-blinded, randomized, placebo-controlled trial (RCT) on vaginal microbiota transplantation (VMT) without antibiotics in women with both symptomatic and asymptomatic vaginal dysbiosis. Forty-nine women were randomly assigned to VMT or placebo. The trial did not show a significant conversion to our predefined Lactobac...

Here, we describe the first placebo-controlled trial of vaginal microbiota transplantation (VMT) in women with asymptomatic dysbiosis without the use of antibiotic pretreatment. Importantly, we also describe the implementation of a donor program and banking of donor cervicovaginal secretions (CVS) while retaining sample viability, which is crucial...

Background: Vaginal dysbiosis covers imbalances in the vaginal microbiota, defined by altered composition of bacteria, viruses, and fungi and is associated with euploid pregnancy losses, premature birth, infertility, or bacterial vaginosis. A large proportion of women who have vaginal dysbiosis do not experience any symptoms. Antibiotics are the t...

Relative abundances of bacterial species in the gut microbiome have been linked to many diseases. Species of gut bacteria are ecologically differentiated by their abilities to metabolize different glycans, making glycan delivery a powerful way to alter the microbiome to promote health. Here, we study the properties and therapeutic potential of chem...

Background Increasing evidence indicates that an altered gut microbiome participates in the development of cardiometabolic syndrome and associated risk factors, such as insulin resistance, dyslipidemia, and obesity, and that targeting the gut microbiome is a promising strategy to lower the risk for cardiometabolic diseases. Part of this reduction i...

Relative abundances of bacterial species in the gut microbiome have been linked to many diseases. Species of gut bacteria are ecologically differentiated by their abilities to metabolize different glycans, making glycan delivery a powerful way to alter the microbiome to promote health. We describe the properties and therapeutic potential of chemica...

The pathogenesis of ulcerative colitis (UC) involves genetic susceptibility, immune-mediated tissue injury and environmental factors including disturbances of the gut microbiota. Nearly all current approved therapies modify host immunity, rather than directly targeting the microbiota. Fecal microbiota transplantation provides encouraging evidence f...

Background Ulcerative colitis (UC) pathogenesis involves genetic susceptibility, immune-mediated tissue injury, and gut microbiota disturbances. Most approved therapies modify host immunity, rather than directly targeting the microbiota. Faecal microbiota transplantation provides encouraging evidence for the therapeutic potential of gut microbiome...

Background The prevention and treatment of bacterial infections is a human health challenge. A disadvantage of antibiotics is that they often kill beneficial commensal, bacteria in addition to, pathogenic bacteria. Indiscriminate killing disrupts the homeostasis between commensal bacteria and the host gut epithelium allowing colonization of the gut...

Background & aims: Enteropathy and small-intestinal ulcers are common adverse effects of nonsteroidal anti-inflammatory drugs such as acetylsalicylic acid (ASA). Safe, cytoprotective strategies are needed to reduce this risk. Specific bifidobacteria might have cytoprotective activities, but little is known about these effects in humans. We used se...

p>The different levels of knowledge described in a translational pipeline (the connection of molecular mechanisms with pre-clinical physiological and human health effects) are not complete for many probiotics. At present, we are not in a position to fully understand the mechanistic basis of many well established probiotic health benefits which, in...

A group of microbiome researchers discuss some of the challenges in developing a new generation of microbiome therapies.

Dietary lipids favor the growth of the pathobiont Bilophila wadsworthia, but the relevance of this expansion in metabolic syndrome pathogenesis is poorly understood. Here, we showed that B. wadsworthia synergizes with high fat diet (HFD) to promote higher inflammation, intestinal barrier dysfunction and bile acid dysmetabolism, leading to higher gl...

The rapid rise in microbiome and probiotic science has led to estimates of product creation and sales exceeding $50 billion within five years. However, many people do not have access to affordable products, and regulatory agencies have stifled progress. The objective of a discussion group at the 2017 meeting of the International Scientific Associat...

Enterococci, in particular vancomycin-resistant enterococci (VRE), are a leading cause of hospital-acquired infections. Promoting intestinal resistance against enterococci could reduce the risk of VRE infections. We investigated the effects of two Lactobacillus strains to prevent intestinal VRE. We used an intestinal colonisation mouse model based...

Technical variation in metagenomic analysis must be minimized to confidently assess the contributions of microbiota to human health. Here we tested 21 representative DNA extraction protocols on the same fecal samples and quantified differences in observed microbial community composition. We compared them with differences due to library preparation...

Objective: Brain-gut-microbiota interactions may play an important role in human health and behavior. However, while rodent models have demonstrated effects of the gut microbiota on emotional, nociceptive and social behaviors, there is little translational human evidence to date. In this study we identify brain and behavioral characteristics of he...

Growing evidence supports the efficacy of many probiotic strains in the management of gastrointestinal disorders associated with deregulated intestinal barrier function and/or structure. In particular, bifidobacteria have been studied for their efficacy to both prevent and treat a broad spectrum of animal and/or human gut disorders. The aim of the...

Resident gut microbes co-exist with transient bacteria to form the gut microbiota. Despite increasing evidence suggesting a role for transient microbes on gut microbiota function, the interplay between resident and transient members of this microbial community is poorly defined. We aimed to determine the extent to which a host's autochthonous gut m...

Background and objectives: Identification of new targets for metabolic diseases treatment or prevention is required. In this context, FIAF/ANGPTL4 appears as a crucial regulator of energy homeostasis. Lactobacilli are often considered to display beneficial effect for their hosts, acting on different regulatory pathways. The aim of the present work...

Significance Microbes hold promise as an inflammatory bowel disease (IBD) therapy. Lactococcus lactis , which has not been appreciated as a beneficial microbe, attenuated colitis in three preclinical mouse IBD models. Neither colonization nor an intact bacterium throughout the colon per se was required. Rather, host lysozyme-mediated lysis in an in...

The human gut contains a highly diverse microbial community that is essentially an open ecosystem, despite being deeply embedded within the human body. Food-associated fermentative bacteria, including probiotics, are major sources of ingested bacteria that may temporarily complement resident microbial communities, thus forming part of our transient...

The gut microbiota (GM) consists of resident commensals and transient microbes conveyed by the diet but little is known about the role of the latter on GM homeostasis. Here we show, by a conjunction of quantitative metagenomics, in silico genome reconstruction and metabolic modeling, that consumption of a fermented milk product containing dairy sta...

Many analyses of the human gut microbiome depend on a catalog of reference genes. Existing catalogs for the human gut microbiome are based on samples from single cohorts or on reference genomes or protein sequences, which limits coverage of global microbiome diversity. Here we combined 249 newly sequenced samples of the Metagenomics of the Human In...

Structural disruption of gut microbiota and associated inflammation are considered important etiological factors in high fat diet (HFD)-induced metabolic syndrome (MS). Three candidate probiotic strains, Lactobacillus paracasei CNCM I-4270 (LC), L. rhamnosus I-3690 (LR) and Bifidobacterium animalis subsp. lactis I-2494 (BA), were individually admin...

Bifidobacterium animalis subsp. lactis CNCM I-2494 is a component of a commercialized fermented dairy product for which beneficial effects on health has been studied by clinical and preclinical trials. To date little is known about the molecular mechanisms that could explain the beneficial effects that bifidobacteria impart to the host. Restriction...

Bifidobacterium animalis subsp. lactis CNCM I-2494 is a component of a commercialized fermented dairy product for which beneficial effects on health has been studied by clinical and preclinical trials. To date little is known about the molecular mechanisms that could explain the beneficial effects that bifidobacteria impart to the host. Restriction...

Bifidobacterium animalis subsp. lactis CNCM I-2494 is a component of a commercialized fermented dairy product for which beneficial effects on health has been studied by clinical and preclinical trials. To date little is known about the molecular mechanisms that could explain the beneficial effects that bifidobacteria impart to the host. Restriction...

Dysregulated immune responses to gut microbes are central to inflammatory bowel disease (IBD), and gut microbial activity can fuel chronic inflammation. Examining how IBD-directed therapies influence gut microbiomes may identify microbial community features integral to mitigating disease and maintaining health. However, IBD patients often receive m...

A Lactobacillus paracasei subs, paracasei strain, for use for accelerating the decrease of Enterococcus faecalis in the intestinal microbiota of a subject haying an intestinal dysbiosis caused by antibiotics.

We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previo...

Lactobacillus paracasei is a member of the normal human and animal gut microbiota and is used extensively in the food industry in starter cultures for dairy products or as probiotics. With the development of low-cost, high-throughput sequencing techniques it has become feasible to sequence many different strains of one species and to determine its...

Reference L. (para)casei strains and genomes. (DOCX)

Encoded functions on (putative) plasmids and on the putative inserted plasmid/transposon region. (DOCX)

CRISPR analysis. (DOCX)

Comparison of MLST and CRISPR typing of strains. Neighbor-joining tree based on seven MLST gene sequences (fusA, ileS, leuS, lepA, pyrG, recA, recG) used previously [13]. Sequence type (ST) and CRISPR type (CT) are given for each strain. CT numbers −1 and 0 designate strains with no PCR amplification and strains with no CRISPR locus, respectively....

Examples of putative Lactobacillus paracasei plasmids (or their fragments). (DOCX)

Overview of significant gene-trait matching results corresponding to growth of strains in the presence of different sugars. (XLSX)

Statistics of L. paracasei genome sequencing. (XLSX)

CRISPR loci variants. A/ Lcas1 sequences of the direct repeats and spacers, B/ Lcas2 sequences of the direct repeats and spacers. (XLSX)

We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previo...

Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal inf...

Experimental evolution is a powerful approach to unravel how selective forces shape microbial genotypes and phenotypes. To this date, the available examples focus on the adaptation to conditions specific to the laboratory. The lactic acid bacterium Lactococcus lactis naturally occurs on plants and in dairy environments, and it is proposed that dair...

Bifidobacterium animalis subsp. lactis CNCM I-2494 is part of a commercialized fermented dairy product with documented health benefits revealed by multiple randomized placebo-controlled clinical trials. Here we report the complete genome sequence of this strain, which has a circular genome of 1,943,113 bp with 1,660 open reading frames and 4 riboso...

In the past decade it has become clear that the lactic acid bacterium Lactobacillus plantarum occupies a diverse range of environmental niches and has an enormous diversity in phenotypic properties, metabolic capacity and industrial applications. In this review, we describe how genome sequencing, comparative genome hybridization and comparative gen...

Diversity in presence/absence of gene clusters in 42 L. plantarum strains in part of the sugar life-style island region, according to CGH analysis.

The medicinal properties of various nutritional components have been appreciated since ancient times. Hippocrates (460–377 B.C.), for example, stated: “Let medicine be thy food and food be thy medicine”. Tea brewed from various fruits, shrubs and trees containing NATURAL salicylates, has been consumed for pain relief since the Stone Age. Also the o...

With the advent of the -omics era, classical technology platforms, such as hyphenated mass spectrometry, are currently undergoing a transformation toward high-throughput application. These novel platforms yield highly detailed metabolite profiles in large numbers of samples. Such profiles can be used as fingerprints for the accurate identification...

A high-resolution amplified fragment length polymorphism (AFLP) methodology was developed to achieve the delineation of closely related Lactococcus lactis strains. The differentiation depth of 24 enzyme-primer-nucleotide combinations was experimentally evaluated to maximize the number of polymorphisms. The resolution depth was confirmed by performi...

Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robus...

Annotation of variable gene clusters and genes.

List of core chromosomal OGs (chrOGs) of the L. lactis genome. The list includes the genes in these chrOGs in the four reference genomes. The three different worksheets are sorted according to (i) our OG number, (ii) LaCOG number and (iii) functional annotation of the KF147 gene products.

List of subspecies‐specific and niche‐specific chromosomal OGs.

Known L. lactis plasmids represented on the CGH microarray.

List of L. lactis‐specific core chrOGs and genes.

Predicted presence/absence of important known plasmid‐located genes in 39 L. lactis strains.