Homeostasis of the gut barrier and potential biomarkers Wells, Jerry M; Brummer, Robert J; Derrien, Muriel ...
American journal of physiology: Gastrointestinal and liver physiology,
03/2017, Letnik:
312, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of secretory IgA (sIgA) and ...antimicrobial peptides and proteins. With the exception of sIgA, expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine. A healthy microbiota plays a key role influencing epithelial barrier functions through the production of short-chain fatty acids (SCFAs) and interactions with innate pattern recognition receptors in the mucosa, driving the steady-state expression of mucus and antimicrobial factors. However, perturbation of gut barrier homeostasis can lead to increased inflammatory signaling, increased epithelial permeability, and dysbiosis of the microbiota, which are recognized to play a role in the pathophysiology of a variety of gastrointestinal disorders. Additionally, gut-brain signaling may be affected by prolonged mucosal immune activation, leading to increased afferent sensory signaling and abdominal symptoms. In turn, neuronal mechanisms can affect the intestinal barrier partly by activation of the hypothalamus-pituitary-adrenal axis and both mast cell-dependent and mast cell-independent mechanisms. The modulation of gut barrier function through nutritional interventions, including strategies to manipulate the microbiota, is considered a relevant target for novel therapeutic and preventive treatments against a range of diseases. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in intestinal diseases, but there remains a need to explore their use in assessing the effect of nutritional factors on gut barrier function. Future studies should aim to establish normal ranges of available biomarkers and their predictive value for gut health in human cohorts.
Akkermansia muciniphila
has evolved to specialize in the degradation and utilization of host mucus, which it may use as the sole source of carbon and nitrogen. Mucus degradation and fermentation by
...A. muciniphila
are known to result in the liberation of oligosaccharides and subsequent production of acetate, which becomes directly available to microorganisms in the vicinity of the intestinal mucosa. Coculturing experiments of
A
.
muciniphila
with non-mucus-degrading butyrate-producing bacteria
Anaerostipes caccae
,
Eubacterium hallii
, and
Faecalibacterium prausnitzii
resulted in syntrophic growth and production of butyrate. In addition, we demonstrate that the production of pseudovitamin B
12
by
E. hallii
results in production of propionate by
A. muciniphila
, which suggests that this syntrophy is indeed bidirectional. These data are proof of concept for syntrophic and other symbiotic microbe-microbe interactions at the intestinal mucosal interface. The observed metabolic interactions between
A
.
muciniphila
and butyrogenic bacterial taxa support the existence of colonic vitamin and butyrate production pathways that are dependent on host glycan production and independent of dietary carbohydrates. We infer that the intestinal symbiont
A. muciniphila
can indirectly stimulate intestinal butyrate levels in the vicinity of the intestinal epithelial cells with potential health benefits to the host.
The intestinal microbiota is said to be a stable ecosystem where many networks between microorganisms are formed. Here we present a proof of principle study of microbial interaction at the intestinal mucus layer. We show that indigestible oligosaccharide chains within mucus become available for a broad range of intestinal microbes after degradation and liberation of sugars by the species
Akkermansia muciniphila
. This leads to the microbial synthesis of vitamin B
12
, 1,2-propanediol, propionate, and butyrate, which are beneficial to the microbial ecosystem and host epithelial cells.
Background. Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and 95% of RV-associated deaths occur in Africa and Asia where RV vaccines (RVVs) have lower efficacy. ...We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor settings. Methods. We conducted a nested, case-control study comparing prevaccination, fecal microbiome compositions between 6-week old, matched RVV responders and nonresponders in rural Ghana. These infants' microbiomes were then compared with 154 age-matched, healthy Dutch infants' microbiomes, assumed to be RVV responders. Fecal microbiome analysis was performed in all groups using the Human Intestinal Tract Chip. Results. We analyzed findings in 78 Ghanaian infants, including 39 RVV responder and nonresponder pairs. The overall microbiome composition was significantly different between RVV responders and nonresponders (FDR, 0.12), and Ghanaian responders were more similar to Dutch infants than nonresponders (P = .002). RVV response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between both Ghanaian RVV responders and nonresponders (FDR, 0.008 vs 0.003) and Dutch infants and Ghanaian nonresponders (FDR, 0.002 vs 0.009). Conclusions. The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries.
The increasing demand for environmentally friendly production processes of green chemicals and fuels has stimulated research in microbial metabolic engineering. CRISPR-Cas-based tools for genome ...editing and expression control have enabled fast, easy, and accurate strain development for established production platform organisms, such as Escherichia coli and Saccharomyces cerevisiae . However, the growing interest in alternative production hosts, for which genome editing options are generally limited, requires further developing such engineering tools. In this review, we discuss established and emerging CRISPR-Cas-based tools for genome editing and transcription control of model and non-model prokaryotes, and we analyse the possibilities for further improvement and expansion of these tools for next generation prokaryotic engineering.
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.
Summary
The microbiota that colonizes the human intestinal tract is complex and its structure is specific for each of us. In this study we expand the knowledge about the stability of the ...subject‐specific microbiota and show that this ecosystem is stable in short‐term intervals (< 1 year) but also during long periods of time (> 10 years). The faecal microbiota composition of five unrelated and healthy subjects was analysed using a comprehensive and highly reproducible phylogenetic microarray, the HITChip. The results show that the use of antibiotics, application of specific dietary regimes and distant travelling have limited impact on the microbiota composition. Several anaerobic genera, including Bifidobacterium and a number of genera within the Bacteroidetes and the Firmicutes phylum, exhibit significantly higher similarity than the total microbiota. Although the gut microbiota contains subject‐specific species, the presence of which is preserved throughout the years, their relative abundance changes considerably. Consequently, the recently proposed enterotype status appears to be a varying characteristic of the microbiota. Our data show that the intestinal microbiota contains a core community of permanent colonizers, and that environmentally introduced changes of the microbiota throughout adulthood are primarily affecting the abundance but not the presence of specific microbial species.
Variations in the composition of the human intestinal microbiota are linked to diverse health conditions. High-throughput molecular technologies have recently elucidated microbial community structure ...at much higher resolution than was previously possible. Here we compare two such methods, pyrosequencing and a phylogenetic array, and evaluate classifications based on two variable 16S rRNA gene regions.
Over 1.75 million amplicon sequences were generated from the V4 and V6 regions of 16S rRNA genes in bacterial DNA extracted from four fecal samples of elderly individuals. The phylotype richness, for individual samples, was 1,400-1,800 for V4 reads and 12,500 for V6 reads, and 5,200 unique phylotypes when combining V4 reads from all samples. The RDP-classifier was more efficient for the V4 than for the far less conserved and shorter V6 region, but differences in community structure also affected efficiency. Even when analyzing only 20% of the reads, the majority of the microbial diversity was captured in two samples tested. DNA from the four samples was hybridized against the Human Intestinal Tract (HIT) Chip, a phylogenetic microarray for community profiling. Comparison of clustering of genus counts from pyrosequencing and HITChip data revealed highly similar profiles. Furthermore, correlations of sequence abundance and hybridization signal intensities were very high for lower-order ranks, but lower at family-level, which was probably due to ambiguous taxonomic groupings.
The RDP-classifier consistently assigned most V4 sequences from human intestinal samples down to genus-level with good accuracy and speed. This is the deepest sequencing of single gastrointestinal samples reported to date, but microbial richness levels have still not leveled out. A majority of these diversities can also be captured with five times lower sampling-depth. HITChip hybridizations and resulting community profiles correlate well with pyrosequencing-based compositions, especially for lower-order ranks, indicating high robustness of both approaches. However, incompatible grouping schemes make exact comparison difficult.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The adhesion ability to mucin varied greatly among 18
Lactobacillus plantarum
isolates depending on their isolation habitats. Such ability remained at high level even though they were sequentially ...exposed to the gastrointestinal (GI) stresses. The majority of
L. plantarum
isolated from shrimp intestine and about half of food isolates exhibited adhesion ability (51.06–55.04%) about the same as the well-known adhesive
L. plantarum
299v. Interestingly, five infant isolates of CIF17A2, CIF17A4, CIF17A5, CIF17AN2, and CIF17AN8 exhibited extremely high adhesion ranging from 62.69 to 72.06%. Such highly adhesive property correlating to distinctively high cell surface hydrophobicity was significantly weaken after pretreatment with LiCl and guanidine-HCl confirming the entailment of protein moiety. Regarding the draft genome information, all molecular structures of major cell wall-anchored proteins involved in the adhesion based on
L. plantarum
WCSF1, including lp_0964, lp_1643, lp_3114, lp_2486, lp_3127, and lp_3059 orthologues were detected in all isolates. Exceptionally, the gene-trait matching between yeast agglutination assay and the relevant mannose-specific adhesin (lp_1229) encoding gene confirmed the Msa absence in five infant isolates expressed distinctively high adhesion. Interestingly, the predicted flagellin encoding genes (
fliC
) firstly revealed in lp_1643, lp_2486, and lp_3114 orthologues may potentially contribute to such highly adhesive property of these isolates.
The human intestinal tract is colonized by a myriad of microbes that have developed intimate interactions with the host. In healthy individuals, this complex ecosystem remains stable and resilient to ...stressors. There is significant attention on the understanding of the composition and function of this intestinal microbiota in health and disease. Current developments in metaomics and systems biology approaches allow to probe the functional potential and activity of the intestinal microbiota. However, all these approaches inherently suffer from the fact that the information on macromolecules (DNA, RNA and protein) is collected at the ecosystem level. Similarly, all physiological and other information collected from isolated strains relates to pure cultures grown in vitro or in gnotobiotic systems. It is essential to integrate these two worlds of predominantly chemistry and biology by linking the molecules to the cells. Here, we will address the integration of omics- and culture-based approaches with the complexity of the human intestinal microbiota in mind and the mucus-degrading bacteria Akkermansia spp. as a paradigm.
Summary
Lactobacillus plantarum WCFS1 is one of the best studied Lactobacilli, notably as its genome was unravelled over 12 years ago. L. plantarum WCFS1 can be grown to high densities, is amenable ...to genetic transformation and highly robust with a relatively high survival rate during the gastrointestinal passage. In this review, we present and discuss the main insights provided by the functional genomics research on L. plantarum WCFS1 with specific attention for the molecular mechanisms related to its interaction with the human host and its potential to modify the immune system, and induce other health‐related benefits. Whereas most insight has been gained in mouse and other model studies, only five human studies have been reported with L. plantarum WCFS1. Hence NCIMB 8826 (the parental strain of L. plantarum WCFS1) in human trials as to capitalize on the wealth of knowledge that is summarized here.
In this review, we present and discuss the main insight provided by the functional genomics research on L. plantarum WCFS1 with specific attention for the molecular mechanisms related to its interaction with the human host and its potential to modify the immune system, and induce other health‐related benefits.
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