Dispersal strategies shape persistence and evolution of human gut bacteria

Human gut bacterial strains can co-exist with their hosts for decades, but little is known about how these microbes persist and disperse, and evolve thereby. Here, we examined these processes in 5,278 adult and infant fecal metagenomes, longitudinally sampled in individuals and families. Our analyses revealed that a subset of gut species is extremely persistent in individuals, families, and geographic regions, represented often by locally successful strains of the phylum Bacteroidota. These ''tenacious'' bacteria show high levels of genetic adaptation to the human host but a high probability of loss upon antibiotic interventions. By contrast, heredipersistent bacteria, notably Firmicutes, often rely on dispersal strategies with weak phylogeographic patterns but strong family transmissions, likely related to sporulation. These analyses describe how different dispersal strategies can lead to the long-term persistence of human gut microbes with implications for gut flora modulations

Conjugated C-6 hydroxylated bile acids in serum relate to human metabolic health and gut Clostridia species

Knowledge about in vivo effects of human circulating C-6 hydroxylated bile acids (BAs), also called muricholic acids, is sparse. It is unsettled if the gut microbiome might contribute to their biosynthesis. Here, we measured a range of serum BAs and related them to markers of human metabolic health and the gut microbiome. We examined 283 non-obese and obese Danish adults from the MetaHit study. Fasting concentrations of serum BAs were quantified using ultra-performance liquid chromatography-tandem mass-spectrometry. The gut microbiome was characterized with shotgun metagenomic sequencing and genome-scale metabolic modeling. We find that tauro- and glycohyocholic acid correlated inversely with body mass index (P = 4.1e-03, P = 1.9e-05, respectively), waist circumference (P = 0.017, P = 1.1e-04, respectively), body fat percentage (P = 2.5e-03, P = 2.3e-06, respectively), insulin resistance (P = 0.051, P = 4.6e-4, respectively), fasting concentrations of triglycerides (P = 0.06, P = 9.2e-4, respectively) and leptin (P = 0.067, P = 9.2e-4). Tauro- and glycohyocholic acids, and tauro-a-muricholic acid were directly linked with a distinct gut microbial community primarily composed of Clostridia species (P = 0.037, P = 0.013, P = 0.027, respectively). We conclude that serum conjugated C-6-hydroxylated BAs associate with measures of human metabolic health and gut communities of Clostridia species. The findings merit preclinical interventions and human feasibility studies to explore the therapeutic potential of these BAs in obesity and type 2 diabetes.Peer reviewe

IgG and IgM cooperate in coating of intestinal bacteria in IgA deficiency

Immunoglobulin A (IgA) is acknowledged to play a role in the defence of the mucosal barrier by coating microorganisms. Surprisingly, IgA-deficient humans exhibit few infection-related complications, raising the question if the more specific IgG may help IgM in compensating for the lack of IgA. Here we employ a cohort of IgA-deficient humans, each paired with IgA-sufficient household members, to investigate multi-Ig bacterial coating. In IgA-deficient humans, IgM alone, and together with IgG, recapitulate coating of most bacterial families, despite an overall 3.6-fold lower Ig-coating. Bacterial IgG coating is dominated by IgG1 and IgG4. Single-IgG2 bacterial coating is sparse and linked to enhanced Escherichia coli load and TNF-α. Although single-IgG2 coating is 1.6-fold more prevalent in IgA deficiency than in healthy controls, it is 2-fold less prevalent than in inflammatory bowel disease. Altogether we demonstrate that IgG assists IgM in coating of most bacterial families in the absence of IgA and identify single-IgG2 bacterial coating as an inflammatory marker.</p

Metabolomics in early life and the association with body composition at age 2 years

Funder: Danone Nutricia Research; Id: http://dx.doi.org/10.13039/100015766Summary: Background and Objectives: Early life is a critical window for adiposity programming. Metabolic‐profile in early life may reflect this programming and correlate with later life adiposity. We investigated if metabolic‐profile at 3 months of age is predictive for body composition at 2 years and if there are differences between boys and girls and between infant feeding types. Methods: In 318 healthy term‐born infants, we determined body composition with skinfold measurements and abdominal ultrasound at 3 months and 2 years of age. High‐throughput‐metabolic‐profiling was performed on 3‐month‐blood‐samples. Using random‐forest‐machine‐learning‐models, we studied if the metabolic‐profile at 3 months can predict body composition outcomes at 2 years of age. Results: Plasma metabolite‐profile at 3 months was found to predict body composition at 2 years, based on truncal: peripheral‐fat‐skinfold‐ratio (T:P‐ratio), with a predictive value of 75.8%, sensitivity of 100% and specificity of 50%. Predictive value was higher in boys (Q2 = 0.322) than girls (Q2 = 0.117). Of the 15 metabolite variables most strongly associated with T:P‐ratio, 11 were also associated with visceral fat at 2 years of age. Conclusion: Several plasma metabolites (LysoPC(22:2), dimethylarginine and others) at 3 months associate with body composition outcome at 2 years. These results highlight the importance of the first months of life for adiposity programming

Conjugated C-6 hydroxylated bile acids in serum relate to human metabolic health and gut Clostridia species

Knowledge about in vivo effects of human circulating C-6 hydroxylated bile acids (BAs), also called muricholic acids, is sparse. It is unsettled if the gut microbiome might contribute to their biosynthesis. Here, we measured a range of serum BAs and related them to markers of human metabolic health and the gut microbiome. We examined 283 non-obese and obese Danish adults from the MetaHit study. Fasting concentrations of serum BAs were quantified using ultra-performance liquid chromatography-tandem mass-spectrometry. The gut microbiome was characterized with shotgun metagenomic sequencing and genome-scale metabolic modeling. We find that tauro- and glycohyocholic acid correlated inversely with body mass index (P = 4.1e-03, P = 1.9e-05, respectively), waist circumference (P = 0.017, P = 1.1e-04, respectively), body fat percentage (P = 2.5e-03, P = 2.3e-06, respectively), insulin resistance (P = 0.051, P = 4.6e-4, respectively), fasting concentrations of triglycerides (P = 0.06, P = 9.2e-4, respectively) and leptin (P = 0.067, P = 9.2e-4). Tauro- and glycohyocholic acids, and tauro-a-muricholic acid were directly linked with a distinct gut microbial community primarily composed of Clostridia species (P = 0.037, P = 0.013, P = 0.027, respectively). We conclude that serum conjugated C-6-hydroxylated BAs associate with measures of human metabolic health and gut communities of Clostridia species. The findings merit preclinical interventions and human feasibility studies to explore the therapeutic potential of these BAs in obesity and type 2 diabetes.</p

Towards the biogeography of prokaryotic genes

Funding was provided by the European Union’s Horizon 2020 Research and Innovation Programme (grant 686070: DD-DeCaF to P.B.) and Marie Skłodowska-Curie Actions (grant 713673 to A.R.d.R.), the European Research Council (ERC) MicrobioS (ERC-AdG-669830 to P.B.), JTC project jumpAR (01KI1706 to P.B.), a BMBF Grant (grant 031L0181A: LAMarCK to P.B.), the European Molecular Biology Laboratory (P.B.), the ETH and Helmut Horten Foundation (S.S.), the National Key R&D Program of China (grant 2020YFA0712403 to X.-M.Z.), (grant 61932008 to X.-M.Z.; grant 61772368 to X.-M.Z.; grant 31950410544 to L.P.C.), the Shanghai Municipal Science and Technology Major Project (grant 2018SHZDZX01 to X.-M.Z. and L.P.C.) and Zhangjiang Lab (X.-M.Z. and L.P.C.), the International Development Research Centre (grant 109304, EMBARK under the JPI AMR framework; to L.P.C.), la Caixa Foundation (grant 100010434, fellowship code LCF/BQ/DI18/11660009 to A.R.d.R.), the Severo Ochoa Program for Centres of Excellence in R&D from the Agencia Estatal de Investigación of Spain (grant SEV-2016-0672 (2017–2021) to C.P.C.), the Ministerio de Ciencia, Innovación y Universidades (grant PGC2018-098073-A-I00 MCIU/AEI/FEDER to J.H.-C. and J.G.-L.), the Innovation Fund Denmark (grant 4203-00005B, PNM), the Biotechnology and Biological Sciences research Council (BBSrC) Gut MicroInstitute Strategic Programmebes and Health BB/r012490/1 and its constituent project BBS/e/F/000Pr10355 (F.H.). R.A. is a member of the Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences.Peer reviewe

Data_Sheet_1_Effects of addition of 2-fucosyllactose to infant formula on growth and specific pathways of utilization by Bifidobacterium in healthy term infants.xlsx

Oligosaccharides in human milk support health via intestinal microbiome. We studied effects of addition of 2-fucosyllactose (2′FL) to the infant formula on infant growth, occurrence of adverse events (AE), and infant microbiome, including expression of microbial genes that metabolize 2′FL. Our hypothesis was that while 2′FL would not affect growth, it would cause changes in microbiome metabolism. In a double-blinded randomized controlled study fashion, the infant formula ± 2′FL or human milk was fed to healthy term infants for 16 weeks. Fecal samples obtained at baseline and week 16 were analyzed for microbial populations, metagenomic species concept (MGS), and genetics of gut metabolic modules (GMMs). There were no effects of addition of 2′FL on growth or AEs. There were no significant differences by feeding group in MGS richness or Shannon diversity at baseline, but formula groups each had significantly greater richness (p < 0.05) and diversity (p < 0.05) after 16 weeks of feeding than the breastfed group. While two glycosyl hydrolase (GH) families (GH42 and GH112) were significantly increased, two other GH families (GH20 and GH2) were significantly decreased in the test formula group compared to the control formula group; although modest, addition of 2′FL resulted in changes in microbiome in the direction of breastfed infants, consistent with internal metabolism of HMOs by Bifidobacterium.</p