Colonisation of the colonic mucus gel layer with butyrogenic and hydrogenotropic bacteria in health and ulcerative colitis

AbstractButyrate is the primary energy source for colonocytes and is essential for mucosal integrity and repair. Butyrate deficiency as a result of colonic dysbiosis is a putative factor in ulcerative colitis (UC). Commensal microbes are butyrogenic, while others may inhibit butyrate, through hydrogenotropic activity. The aim of this study was to quantify butyrogenic and hydrogenotropic species and determine their relationship with inflammation within the colonic mucus gel layer (MGL). Mucosal brushings were obtained from 20 healthy controls (HC), 20 patients with active colitis (AC) and 14 with quiescent colitis (QUC). Abundance of each species was determined by RT-PCR. Inflammatory scores were available for each patient. Statistical analyses were performed using Mann–Whitney-U and Kruskall-Wallis tests. Butyrogenic R. hominis was more abundant in health than UC (p < 0.005), prior to normalisation against total bacteria. Hydrogenotropic B. wadsworthia was reduced in AC compared to HC and QUC (p < 0.005). An inverse correlation existed between inflammation and R. hominis (ρ − 0.460, p < 0.005) and B. wadsworthia (ρ − 0.646, p < 0.005). Other hydrogenotropic species did not widely colonise the MGL. These data support a role for butyrogenic bacteria in UC. Butyrate deficiency in UC may be related to reduced microbial production, rather than inhibition by microbial by-products.

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Colonisation of the Colonic Mucus Gel Layer With Butyrogenic and Hydrogenotropic Bacteria in Health and Ulcerative Colitis

10.21203/rs.3.rs-115020/v1 ◽

2020 ◽

Author(s):

Helen Earley ◽

Grainne Lennon ◽

Desmond Winter ◽

Calvin Coffey ◽

Ronan O'Connell

Keyword(s):

Ulcerative Colitis ◽

Inverse Correlation ◽

Inhibitory Effect ◽

Primary Energy ◽

Rt Pcr ◽

Mucosal Integrity ◽

Gel Layer ◽

Active Colitis ◽

Mucus Gel ◽

By Products

Abstract Butyrate is the primary energy source for colonocytes and is essential for mucosal integrity and repair. Butyrate deficiency as a result of colonic dysbiosis is a putative factor in ulcerative colitis (UC). Commensal microbes are butyrogenic, while others have an inhibitory effect, through hydrogenotropic activity. The aim of this study was to quantify butyrogenic and hydrogenotropic species and determine their relationship with inflammation within the colonic mucus gel layer (MGL).Mucosal brushings were obtained from 20 patients with active colitis (AC), 20 healthy controls (HC) and 14 with quiescent colitis (QUC). Abundance of each species was determined by RT-PCR. Inflammatory scores were available for each patient. Statistical analyses were performed using Mann-Whitney-U and Kruskall-Wallis tests.Butyrogenic R. hominis was more abundant in health than UC (p<0.005). Hydrogenotropic B. wadsworthia was reduced in AC compared to HC and QUC (p<0.005). An inverse correlation existed between inflammation and R. hominis (ρ -0.460, p >0.005) and B. wadsworthia (ρ -0.646, p >0.005). Other hydrogenotropic species did not widely colonise the MGL. These data support a role for butyrogenic and some species of hydrogenotropic bacteria in UC. Butyrate deficiency in UC may be related to reduced microbial production, rather than inhibition by microbial by-products.

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The abundance of Akkermansia muciniphila and its relationship with sulphated colonic mucins in health and ulcerative colitis

Scientific Reports ◽

10.1038/s41598-019-51878-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 14

Author(s):

Helen Earley ◽

Grainne Lennon ◽

Áine Balfe ◽

J. Calvin Coffey ◽

Desmond C. Winter ◽

...

Keyword(s):

Ulcerative Colitis ◽

Relative Proportion ◽

Positive Association ◽

Blue Staining ◽

Alcian Blue Staining ◽

Akkermansia Muciniphila ◽

Colonic Mucin ◽

Markers Of Inflammation ◽

Gel Layer ◽

Mucus Gel

Abstract Akkermansia muciniphila utilises colonic mucin as its substrate. Abundance is reduced in ulcerative colitis (UC), as is the relative proportion of sulphated mucin in the mucus gel layer (MGL). It is unknown if these phenomena are related, however reduced sulphated mucins could contribute to reduced abundance, owing to a lack of substrate. The aim of this study was to quantify A. muciniphila within the MGL and to relate these findings with markers of inflammation and the relative proportion of sulphomucin present. Colonic biopsies and mucus brushings were obtained from 20 patients with active UC (AC), 14 with quiescent UC (QUC) and 20 healthy controls (HC). A. muciniphila abundance was determined by RT-PCR. High iron diamine alcian-blue staining was performed for histological analysis. Patients with AC had reduced abundance of A. muciniphila compared to HC and QUC. A positive association was found between A. muciniphila abundance and higher percentage of sulphated mucin (ρ 0.546, p = 0.000). Lower abundances of A. muciniphila correlated with higher inflammatory scores (ρ = 0.294 (p = 0.001)). This study confirms an inverse relationship between A. muciniphila and inflammation and a positive association between A. muciniphila abundance and percentage of sulfated mucin in the MGL.

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Skate-Skin Mucin, Rich in Sulfated Sugars and Threonine, Promotes Proliferation of Akkermansia muciniphila in Feeding Tests in Rats and In Vitro Fermentation Using Human Feces

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbac003 ◽

2022 ◽

Author(s):

Takaaki Miyata ◽

Takayasu Mizushima ◽

Nobuyuki Miyamoto ◽

Takahiro Yamada ◽

Koji Hase ◽

...

Keyword(s):

Metabolic Disorders ◽

Control Diet ◽

Inverse Correlation ◽

Dietary Factors ◽

Amino Sugars ◽

Human Feces ◽

In Vitro Fermentation ◽

Akkermansia Muciniphila ◽

Total Bacteria

Abstract Dietary factors, affect Akkermansia muciniphila (AM) abundance in the colon, have attracted attention, driven by the inverse correlation between AM abundance and metabolic disorders. We prepared skate-skin mucin (SM), porcine stomach mucin (PM), and rat gastrointestinal mucin (RM). SM contained more sulfated sugars and threonine than PM or RM. Rats were fed a control diet or diets including SM, PM, or RM (15 g/kg), or SM (12 g/kg) from five different threonine contents for 14 d. Cecal total bacteria and AM were less and more numerous, respectively, in SM-fed rats than the others, but SM did not affect microbial species-richness. Low-threonine SM did not induce AM proliferation. The in vitro fermentation with human feces showed that the rate of AM increase was greater with SM than PM. Collectively, heavy SM sulfation facilitates a priority supply of SM-derived amino sugars and threonine that promotes AM proliferation in rats and human feces.

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Histochemical Structure of the Mucus Gel Layer Coating the Fecal Surface of Rodents, Rabbits and Humans

Journal of Nutritional Science and Vitaminology ◽

10.3177/jnsv.51.287 ◽

2005 ◽

Vol 51 (4) ◽

pp. 287-291 ◽

Cited By ~ 3

Author(s):

Akira SHIMOTOYODOME ◽

Shinichi MEGUO ◽

Ichiro TOKIMITSU ◽

Takashi SAKATA

Keyword(s):

Gel Layer ◽

Mucus Gel ◽

Layer Coating

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Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery Systems

Polymers ◽

10.3390/polym12061259 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1259 ◽

Cited By ~ 1

Author(s):

Iram Shahzadi ◽

Andrea Fürst ◽

Zeynep Burcu Akkus-Dagdeviren ◽

Shumaila Arshad ◽

Markus Kurpiers ◽

...

Keyword(s):

Intestinal Mucosa ◽

Polyacrylic Acid ◽

Drug Delivery Systems ◽

Bond Formation ◽

Work Of Adhesion ◽

Gel Layer ◽

Thiol Ligands ◽

Mucus Gel ◽

Ft Ir ◽

Acetyl Cysteine

As less reactive s-protected thiomers can likely interpenetrate the mucus gel layer to a higher extent before getting immobilized via disulfide bond formation with mucins, it was the aim of this study to develop a novel type of s-protected thiomer based on the less reactive substructure cysteine-N-acetyl cysteine (Cys-NAC) in order to obtain improved mucoadhesive properties. For this purpose, two types of s-protected thiomers, polyacrylic acid-cysteine-mercaptonicotinic acid (PAA-Cys-MNA) and polyacrylic acid-cysteine-N-acetyl cysteine (PAA-Cys-NAC), were synthesized and characterized by Fourier-transform infrared spectroscopy (FT-IR) and the quantification of attached disulfide ligands. The viscosity of both products was measured in the presence of NAC and mucus. Both thiomers were also evaluated regarding swelling behavior, tensile studies and retention time on the porcine intestinal mucosa. The FT-IR spectra confirmed the successful attachment of Cys-MNA and Cys-NAC ligands to PAA. The number of attached sulfhydryl groups was in the range of 660–683 µmol/g. The viscosity of both s-protected thiomers increased due to the addition of increasing amounts of NAC. The viscosity of the mucus increased in the presence of 1% PAA-Cys-MNA and PAA-Cys-NAC 5.6- and 10.9-fold, respectively, in comparison to only 1% PAA. Both s-protected thiomers showed higher water uptake than unmodified PAA. The maximum detachment force (MDF) and the total work of adhesion (TWA) increased in the case of PAA-Cys-MNA up to 1.4- and 1.6-fold and up to 2.4- and 2.8-fold in the case of PAA-Cys-NAC. The retention of PAA, PAA-Cys-MNA, and PAA-Cys-NAC on porcine intestinal mucosa was 25%, 49%, and 76% within 3 h, respectively. The results of this study provide evidence that less reactive s-protected thiomers exhibit higher mucoadhesive properties than highly reactive s-protected thiomers.

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Thinning of the Gastric Mucus Gel Layer in H Pylori Positive Subjects with Advancing Age

Age and Ageing ◽

10.1093/ageing/26.suppl_3.p8-c ◽

1997 ◽

Vol 26 (suppl 3) ◽

pp. P8-P8

Author(s):

J Newton ◽

N Jordan ◽

G Williams ◽

A Allen ◽

O James ◽

...

Keyword(s):

Gastric Mucus ◽

Gel Layer ◽

Mucus Gel ◽

H Pylori

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Light microscopical observations on luminally administered dyes, dextrans, nanospheres and microspheres in the pre-epithelial mucus gel layer of the rat distal colon

Journal of Controlled Release ◽

10.1016/s0168-3659(96)01600-8 ◽

1997 ◽

Vol 46 (3) ◽

pp. 233-242 ◽

Cited By ~ 83

Author(s):

László Szentkuti

Keyword(s):

Distal Colon ◽

Gel Layer ◽

Rat Distal Colon ◽

Mucus Gel

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Influences of the colonic microbiome on the mucous gel layer in ulcerative colitis

Gut Microbes ◽

10.4161/gmic.28793 ◽

2014 ◽

Vol 5 (3) ◽

pp. 277-476 ◽

Cited By ~ 17

Author(s):

Gráinne Lennon ◽

Áine Balfe ◽

Helen Earley ◽

Liam A Devane ◽

Aonghus Lavelle ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gel Layer

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Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin

AJP Cell Physiology ◽

10.1152/ajpcell.00102.2004 ◽

2005 ◽

Vol 288 (1) ◽

pp. C1-C19 ◽

Cited By ~ 371

Author(s):

Adrian Allen ◽

Gunnar Flemström

Keyword(s):

Ph Gradient ◽

Support Surface ◽

First Line ◽

Physiological Conditions ◽

Neutral Ph ◽

Primary Function ◽

Gel Layer ◽

Mucus Gel ◽

And Control

Secretion of bicarbonate into the adherent layer of mucus gel creates a pH gradient with a near-neutral pH at the epithelial surfaces in stomach and duodenum, providing the first line of mucosal protection against luminal acid. The continuous adherent mucus layer is also a barrier to luminal pepsin, thereby protecting the underlying mucosa from proteolytic digestion. In this article we review the present state of the gastroduodenal mucus bicarbonate barrier two decades after the first supporting experimental evidence appeared. The primary function of the adherent mucus gel layer is a structural one to create a stable, unstirred layer to support surface neutralization of acid and act as a protective physical barrier against luminal pepsin. Therefore, the emphasis on mucus in this review is on the form and role of the adherent mucus gel layer. The primary function of the mucosal bicarbonate secretion is to neutralize acid diffusing into the mucus gel layer and to be quantitatively sufficient to maintain a near-neutral pH at the mucus-mucosal surface interface. The emphasis on mucosal bicarbonate in this review is on the mechanisms and control of its secretion and the establishment of a surface pH gradient. Evidence suggests that under normal physiological conditions, the mucus bicarbonate barrier is sufficient for protection of the gastric mucosa against acid and pepsin and is even more so for the duodenum.

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