scholarly journals The double-edged sword of gut bacteria in celiac disease and implications for therapeutic potential

Author(s):  
Heather J. Galipeau ◽  
Elena F. Verdu
2013 ◽  
Vol 6 (4) ◽  
pp. 159-184 ◽  
Author(s):  
Anthony Samsel ◽  
Stephanie Seneff

ABSTRACT Celiac disease, and, more generally, gluten intolerance, is a growing problem worldwide, but especially in North America and Europe, where an estimated 5% of the population now suffers from it. Symptoms include nausea, diarrhea, skin rashes, macrocytic anemia and depression. It is a multifactorial disease associated with numerous nutritional deficiencies as well as reproductive issues and increased risk to thyroid disease, kidney failure and cancer. Here, we propose that glyphosate, the active ingredient in the herbicide, Roundup®, is the most important causal factor in this epidemic. Fish exposed to glyphosate develop digestive problems that are reminiscent of celiac disease. Celiac disease is associated with imbalances in gut bacteria that can be fully explained by the known effects of glyphosate on gut bacteria. Characteristics of celiac disease point to impairment in many cytochrome P450 enzymes, which are involved with detoxifying environmental toxins, activating vitamin D3, catabolizing vitamin A, and maintaining bile acid production and sulfate supplies to the gut. Glyphosate is known to inhibit cytochrome P450 enzymes. Deficiencies in iron, cobalt, molybdenum, copper and other rare metals associated with celiac disease can be attributed to glyphosate’s strong ability to chelate these elements. Deficiencies in tryptophan, tyrosine, methionine and selenomethionine associated with celiac disease match glyphosate’s known depletion of these amino acids. Celiac disease patients have an increased risk to non-Hodgkin’s lymphoma, which has also been implicated in glyphosate exposure. Reproductive issues associated with celiac disease, such as infertility, miscarriages, and birth defects, can also be explained by glyphosate. Glyphosate residues in wheat and other crops are likely increasing recently due to the growing practice of crop desiccation just prior to the harvest. We argue that the practice of "ripening" sugar cane with glyphosate may explain the recent surge in kidney failure among agricultural workers in Central America. We conclude with a plea to governments to reconsider policies regarding the safety of glyphosate residues in foods


2021 ◽  
Vol 6 (62) ◽  
pp. eabg4925
Author(s):  
Rahel Frick ◽  
Lene S. Høydahl ◽  
Jan Petersen ◽  
M. Fleur du Pré ◽  
Shraddha Kumari ◽  
...  

Antibodies specific for peptides bound to human leukocyte antigen (HLA) molecules are valuable tools for studies of antigen presentation and may have therapeutic potential. Here, we generated human T cell receptor (TCR)–like antibodies toward the immunodominant signature gluten epitope DQ2.5-glia-α2 in celiac disease (CeD). Phage display selection combined with secondary targeted engineering was used to obtain highly specific antibodies with picomolar affinity. The crystal structure of a Fab fragment of the lead antibody 3.C11 in complex with HLA-DQ2.5:DQ2.5-glia-α2 revealed a binding geometry and interaction mode highly similar to prototypic TCRs specific for the same complex. Assessment of CeD biopsy material confirmed disease specificity and reinforced the notion that abundant plasma cells present antigen in the inflamed CeD gut. Furthermore, 3.C11 specifically inhibited activation and proliferation of gluten-specific CD4+ T cells in vitro and in HLA-DQ2.5 humanized mice, suggesting a potential for targeted intervention without compromising systemic immunity.


2015 ◽  
Vol 110 (6) ◽  
pp. 899-908 ◽  
Author(s):  
Guoxian Wei ◽  
Na Tian ◽  
Adriana C Valery ◽  
Yi Zhong ◽  
Detlef Schuppan ◽  
...  

mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Max M. Villa ◽  
Rachael J. Bloom ◽  
Justin D. Silverman ◽  
Heather K. Durand ◽  
Sharon Jiang ◽  
...  

ABSTRACT Culture and screening of gut bacteria enable testing of microbial function and therapeutic potential. However, the diversity of human gut microbial communities (microbiota) impedes comprehensive experimental studies of individual bacterial taxa. Here, we combine advances in droplet microfluidics and high-throughput DNA sequencing to develop a platform for separating and assaying growth of microbiota members in picoliter droplets (MicDrop). MicDrop enabled us to cultivate 2.8 times more bacterial taxa than typical batch culture methods. We then used MicDrop to test whether individuals possess similar abundances of carbohydrate-degrading gut bacteria, using an approach which had previously not been possible due to throughput limitations of traditional bacterial culture techniques. Single MicDrop experiments allowed us to characterize carbohydrate utilization among dozens of gut bacterial taxa from distinct human stool samples. Our aggregate data across nine healthy stool donors revealed that all of the individuals harbored gut bacterial species capable of degrading common dietary polysaccharides. However, the levels of richness and abundance of polysaccharide-degrading species relative to monosaccharide-consuming taxa differed by up to 2.6-fold and 24.7-fold, respectively. Additionally, our unique dataset suggested that gut bacterial taxa may be broadly categorized by whether they can grow on single or multiple polysaccharides, and we found that this lifestyle trait is correlated with how broadly bacterial taxa can be found across individuals. This demonstration shows that it is feasible to measure the function of hundreds of bacterial taxa across multiple fecal samples from different people, which should in turn enable future efforts to design microbiota-directed therapies and yield new insights into microbiota ecology and evolution. IMPORTANCE Bacterial culture and assay are components of basic microbiological research, drug development, and diagnostic screening. However, community diversity can make it challenging to comprehensively perform experiments involving individual microbiota members. Here, we present a new microfluidic culture platform that makes it feasible to measure the growth and function of microbiota constituents in a single set of experiments. As a proof of concept, we demonstrate how the platform can be used to measure how hundreds of gut bacterial taxa drawn from different people metabolize dietary carbohydrates. Going forward, we expect this microfluidic technique to be adaptable to a range of other microbial assay needs.


2021 ◽  
Vol 8 ◽  
Author(s):  
Maria Carolina Rodríguez-Daza ◽  
Elena C. Pulido-Mateos ◽  
Joseph Lupien-Meilleur ◽  
Denis Guyonnet ◽  
Yves Desjardins ◽  
...  

The genome of gut microbes encodes a collection of enzymes whose metabolic functions contribute to the bioavailability and bioactivity of unabsorbed (poly)phenols. Datasets from high throughput sequencing, metabolome measurements, and other omics have expanded the understanding of the different modes of actions by which (poly)phenols modulate the microbiome conferring health benefits to the host. Progress have been made to identify direct prebiotic effects of (poly)phenols; albeit up to date, these compounds are not recognized as prebiotics sensu stricto. Interestingly, certain probiotics strains have an enzymatic repertoire, such as tannase, α-L-rhamnosidase, and phenolic acid reductase, involved in the transformation of different (poly)phenols into bioactive phenolic metabolites. In vivo studies have demonstrated that these (poly)phenol-transforming bacteria thrive when provided with phenolic substrates. However, other taxonomically distinct gut symbionts of which a phenolic-metabolizing activity has not been demonstrated are still significantly promoted by (poly)phenols. This is the case of Akkermansia muciniphila, a so-called antiobesity bacterium, which responds positively to (poly)phenols and may be partially responsible for the health benefits formerly attributed to these molecules. We surmise that (poly)phenols broad antimicrobial action free ecological niches occupied by competing bacteria, thereby allowing the bloom of beneficial gut bacteria. This review explores the capacity of (poly)phenols to promote beneficial gut bacteria through their direct and collaborative bacterial utilization and their inhibitory action on potential pathogenic species. We propose the term duplibiotic, to describe an unabsorbed substrate modulating the gut microbiota by both antimicrobial and prebiotic modes of action. (Poly)phenol duplibiotic effect could participate in blunting metabolic disturbance and gut dysbiosis, positioning these compounds as dietary strategies with therapeutic potential.


2019 ◽  
Vol 42 ◽  
Author(s):  
Kevin B. Clark

Abstract Some neurotropic enteroviruses hijack Trojan horse/raft commensal gut bacteria to render devastating biomimicking cryptic attacks on human/animal hosts. Such virus-microbe interactions manipulate hosts’ gut-brain axes with accompanying infection-cycle-optimizing central nervous system (CNS) disturbances, including severe neurodevelopmental, neuromotor, and neuropsychiatric conditions. Co-opted bacteria thus indirectly influence host health, development, behavior, and mind as possible “fair-weather-friend” symbionts, switching from commensal to context-dependent pathogen-like strategies benefiting gut-bacteria fitness.


2001 ◽  
Vol 120 (5) ◽  
pp. A684-A684
Author(s):  
D TRAPP ◽  
W DIETERICH ◽  
H WIESER ◽  
M LEIDENBERGER ◽  
D SEILMEIER ◽  
...  

2001 ◽  
Vol 120 (5) ◽  
pp. A395-A395
Author(s):  
J WEST ◽  
A LLOYD ◽  
P HILL ◽  
G HOLMES

2001 ◽  
Vol 120 (5) ◽  
pp. A393-A393
Author(s):  
M GABRIELLI ◽  
C PADALINO ◽  
E LEO ◽  
S DANESE ◽  
G FIORE ◽  
...  

2001 ◽  
Vol 120 (5) ◽  
pp. A392-A392
Author(s):  
J FERRETI ◽  
R MAZURE ◽  
P TANOUE ◽  
A MARINO ◽  
G COINTRY ◽  
...  

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