Bridging Bacteria and the Gut: Functional Aspects of Type IV Pili

Cell-surface-located proteinaceous appendages, such as flagella and fimbriae or pili, are ubiquitous in bacterial communities. Here, we focus on conserved type IV pili (T4P) produced by bacteria in the intestinal tract, one of the most densely populated human ecosystems. Computational analysis revealed that approximately 30% of known intestinal bacteria are predicted to produce T4P. To rationalize how T4P allow intestinal bacteria to interact with their environment, other microbiota members, and host cells, we review their established role in gut commensals and pathogens with respect to adherence, motility, and biofilm formation, as well as protein secretion and DNA uptake. This work indicates that T4P are widely spread among the known members of the intestinal microbiota and that their contribution to human health might be underestimated.Peer reviewe

Akkermansia muciniphila in the Human Gastrointestinal Tract: When, Where, and How?

Akkermansia muciniphila is a mucin-degrading bacterium of the phylum Verrucomicrobia. Its abundance in the human intestinal tract is inversely correlated to several disease states. A. muciniphila resides in the mucus layer of the large intestine, where it is involved in maintaining intestinal integrity. We explore the presence of Akkermansia-like spp. based on its 16S rRNA sequence and metagenomic signatures in the human body so as to understand its colonization pattern in time and space. A. muciniphila signatures were detected in colonic samples as early as a few weeks after birth and likely could be maintained throughout life. The sites where Akkermansia-like sequences (including Verrucomicrobia phylum and/or Akkermansia spp. sequences found in the literature) were detected apart from the colon included human milk, the oral cavity, the pancreas, the biliary system, the small intestine, and the appendix. The function of Akkermansia-like spp. in these sites may differ from that in the mucosal layer of the colon. A. muciniphila present in the appendix or in human milk could play a role in the re-colonization of the colon or breast-fed infants, respectively. In conclusion, even though A. muciniphila is most abundantly present in the colon, the presence of Akkermansia-like spp. along the digestive tract indicates that this bacterium might have more functions than those currently known.Peer reviewe

Arteriography during ex vivo renal perfusion A complication

A case of bilateral renal-cell carcinoma unsuccessfully treated with bench surgery is reported. The reason for failure was apparently the toxicity of the contrast media used during the ex vivo arteriographic studies. © 1973

Action and function of Akkermansia muciniphila in microbiome ecology, health and disease

The discovery of Akkermansia muciniphila has opened new avenues for the use of this abundant intestinal symbiont in next generation therapeutic products, as well as targeting microbiota dynamics. A. muciniphila is known to colonize the mucosal layer of the human intestine where it triggers both host metabolic and immune responses. A. muciniphila is particularly effective in increasing mucus thickness and increasing gut barrier function. As a result host metabolic markers ameliorate. The mechanism of host regulation is thought to involve the outer membrane composition, including the type IV pili of A. muciniphila, that directly signal to host immune receptors. At the same time the metabolic activity of A. muciniphila leads to the production of short chain fatty acids that are beneficial to the host and microbiota members. This contributes to host-microbiota and microbe-microbe syntrophy The mucolytic activity and metabolite production make A. muciniphila a key species in the mucus layer, stimulating beneficial mucosal microbial networks. This well studied member of the microbiota has been studied in three aspects that will be further described in this review: i) A. muciniphila characteristics and mucin adaptation, ii) its role as key species in the mucosal microbiome, and iii) its role in host health. (C) 2017 Published by Elsevier Ltd.Peer reviewe

Oral treatment with Eubacterium hallii improves insulin sensitivity in db/db mice

F.B. is supported by Swedish Research Council, Swedish Diabetes Foundation, Swedish Heart Lung Foundation, Swedish Foundation for Strategic Research, Knut and Alice Wallenberg foundation, Göran Gustafsson Foundation, Ingbritt and Arne Lundberg’s foundation, Swedish Heart Lung Foundation, Torsten Söderberg’s Foundation, Ragnar Söderberg’s Foundation, NovoNordisk Foundation, AFA insurances, and LUA-ALF grants from Västra Götalandsregionen and Stockholm County Council. F.B. is a recipient of ERC Consolidator Grant (European Research Council, Consolidator grant 615362—METABASE). W.M.d.V. is supported by the Finland Academy of Sciences (grants 137389, 141140 and 1272870 ), the Netherlands Organization for Scientific Research (Spinoza Award and SIAM Gravity Grant 024.002.002) and the European Research Council (ERC Advanced Grant 250172 MicrobesInside). M.N. is supported by a ZONMW-VIDI grant 2013 (016.146.327).Peer reviewedPublisher PD

Dynamic metabolic interactions and trophic roles of human gut microbes identified using a minimal microbiome exhibiting ecological properties

Microbe-microbe interactions in the human gut are influenced by host-derived glycans and diet. The high complexity of the gut microbiome poses a major challenge for unraveling the metabolic interactions and trophic roles of key microbes. Synthetic minimal microbiomes provide a pragmatic approach to investigate their ecology including metabolic interactions. Here, we rationally designed a synthetic microbiome termed Mucin and Diet based Minimal Microbiome (MDb-MM) by taking into account known physiological features of 16 key bacteria. We combined 16S rRNA gene-based composition analysis, metabolite measurements and metatranscriptomics to investigate community dynamics, stability, inter-species metabolic interactions and their trophic roles. The 16 species co-existed in the in vitro gut ecosystems containing a mixture of complex substrates representing dietary fibers and mucin. The triplicate MDb-MM's followed the Taylor's power law and exhibited strikingly similar ecological and metabolic patterns. The MDb-MM exhibited resistance and resilience to temporal perturbations as evidenced by the abundance and metabolic end products. Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem.Peer reviewe

Risk factors for renal allograft loss in patients with systemic lupus erythematosus

Risk factors for renal allograft loss in patients with systemic lupus erythematosus. Controversy exists regarding the risk factors for renal allograft loss in patients with systemic lupus erythematosus (SLE). This study is a retrospective evaluation of each of these independent risk factors in 80 renal transplants for ESRD secondary to SLE done at our institution between 1971 and 1994. Our entire non-diabetic cohort of 1,966 renal transplants is used as a comparison group. Our results showed equivalent graft survival rates between lupus patients and the cohort at 1, 5 and 10 years (P = 0.56). However, an analysis of cyclosporine-era cadaver grafts revealed that the lupus group had poorer 5-year graft survival than the cohort (41% vs. 71%, P = 0.02). Evaluation of cyclosporine-era lupus graft survival showed significantly improved out-come in living-related lupus recipients over cadaver grafts at five years (89% vs. 41%, P = 0.003). The majority of grafts lost in the lupus cadaver recipients were due to chronic rejection. Rejection was increased in lupus recipients: 69% of lupus patients experienced rejection in the first year compared to 58% of controls (P = 0.01). Stratified for age, sex, race and cyclosporine use, this difference remained significant (P = 0.003, relative risk 1.7). Nephrectomy, splenectomy and 3 to 6 months of pretransplant dialysis did not improve graft survival. A dialysis duration of greater than 25 months predicted worse graft survival (P = 0.01). Among lupus patients, PRA did not correlate with graft outcome (P = 0.5), and HLA-identical cadaver grafts had improved outcomes compared to cadaver grafts. We conclude that acute and chronic rejection are the major risk factors for graft loss in lupus patients. The superior outcome of living-related over cadaver grafts in lupus patients suggests an increased role for living-related grafts. Pretransplant dialysis, nephrectomy and splenectomy are not indicated

Antiretroviral Therapy outcomes among adolescents and youth in rural Zimbabwe

Around 2 million adolescents and 3 million youth are estimated to be living with HIV worldwide. Antiretroviral outcomes for this group appear to be worse compared to adults. We report antiretroviral therapy outcomes from a rural setting in Zimbabwe among patients aged 10-30 years who were initiated on ART between 2005 and 2008. The cohort was stratified into four age groups: 10-15 (young adolescents) 15.1-19 years (adolescents), 19.1-24 years (young adults) and 24.1-29.9 years (older adults). Survival analysis was used to estimate rates of deaths and loss to follow-up stratified by age group. Endpoints were time from ART initiation to death or loss to follow-up. Follow-up of patients on continuous therapy was censored at date of transfer, or study end (31 December 2008). Sex-adjusted Cox proportional hazards models were used to estimate hazard ratios for different age groups. 898 patients were included in the analysis; median duration on ART was 468 days. The risk of death were highest in adults compared to young adolescents (aHR 2.25, 95%CI 1.17-4.35). Young adults and adolescents had a 2-3 times higher risk of loss to follow-up compared to young adolescents. When estimating the risk of attrition combining loss to follow-up and death, young adults had the highest risk (aHR 2.70, 95%CI 1.62-4.52). This study highlights the need for adapted adherence support and service delivery models for both adolescents and young adults

Akkermansia muciniphila and its role in regulating host functions

Akkermansia muciniphila is an intestinal bacterium that was isolated a decade ago from a human fecal sample. Its specialization in mucin degradation makes it a key organism at the mucosal interface between the lumen and host cells. Although it was isolated quite recently, it has rapidly raised significant interest as A. muciniphila is the only cultivated intestinal representative of the Verrucomicrobia, one of the few phyla in the human gut that can be easily detected in phylogenetic and metagenome analyses. There has also been a growing interest in A. muciniphila, due to its association with health in animals and humans. Notably, reduced levels of A. muciniphila have been observed in patients with inflammatory bowel diseases (mainly ulcerative colitis) and metabolic disorders, which suggests it may have potential anti-inflammatory properties. The aims of this review are to summarize the existing data on the intestinal distribution of A. muciniphila in health and disease, to provide insight into its ecology and its role in founding microbial networks at the mucosal interface, as well as to discuss recent research on its role in regulating host functions that are disturbed in various diseases, with a specific focus on metabolic disorders in both animals and humans. (C) 2016 Elsevier Ltd. All rights reserved.Peer reviewe