Small intestinal levels of the branched short-chain fatty acid isovalerate are elevated during infection with Heligmosomoides polygyrus and can promote helminth fecundity

Heligmosomoides polygyrus is a helminth which naturally infects mice and is widely used as a laboratory model of chronic small intestinal helminth infection. While it is known that infection with H. polygyrus alters the composition of the host’s bacterial microbiota, the functional implications of this alteration are unclear. We investigated the impact of H. polygyrus infection on short-chain fatty acid (SCFA) levels in the mouse intestine and sera. We found that helminth infection resulted in significantly upregulated levels of the branched SCFA isovaleric acid, exclusively in the proximal small intestine, which is the site of H. polygyrus colonization. We next set out to test the hypothesis that elevating local levels of isovaleric acid was a strategy used by H. polygyrus to promote its own fitness within the mammalian host. To test this, we supplemented the drinking water of mice with isovalerate during H. polygyrus infection and examined whether this affected helminth fecundity or chronicity. We did not find that isovaleric acid supplementation affected helminth chronicity, however, we found that it did promote helminth fecundity, as measured by helminth egg output in the feces of mice. Through antibiotic-treatment of helminth-infected mice, we found that the bacterial microbiota was required in order to support elevated levels of isovaleric acid in the proximal small intestine during helminth infection. Overall, our data reveal that during H. polygyrus infection there is a microbiota-dependent localized increase in the production of isovaleric acid in the proximal small intestine and this supports helminth fecundity in the murine host.

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Impaired host resistance to Salmonella during helminth co-infection is restored by anthelmintic treatment prior to bacterial challenge

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009052 ◽

2021 ◽

Vol 15 (1) ◽

pp. e0009052

Author(s):

Tara P. Brosschot ◽

Katherine M. Lawrence ◽

Brandon E. Moeller ◽

Mia H. E. Kennedy ◽

Rachael D. FitzPatrick ◽

...

Keyword(s):

Small Intestine ◽

Host Resistance ◽

Helminth Infection ◽

Bacterial Colonization ◽

Drug Clearance ◽

Anthelmintic Treatment ◽

Intestinal Lumen ◽

Intestinal Helminth ◽

Heligmosomoides Polygyrus ◽

Small Intestinal

Intestinal helminth infection can impair host resistance to co-infection with enteric bacterial pathogens. However, it is not known whether helminth drug-clearance can restore host resistance to bacterial infection. Using a mouse helminth-Salmonella co-infection system, we show that anthelmintic treatment prior to Salmonella challenge is sufficient to restore host resistance to Salmonella. The presence of the small intestine-dwelling helminth Heligmosomoides polygyrus at the point of Salmonella infection supports the initial establishment of Salmonella in the small intestinal lumen. Interestingly, if helminth drug-clearance is delayed until Salmonella has already established in the small intestinal lumen, anthelmintic treatment does not result in complete clearance of Salmonella. This suggests that while the presence of helminths supports initial Salmonella colonization, helminths are dispensable for Salmonella persistence in the host small intestine. These data contribute to the mechanistic understanding of how an ongoing or prior helminth infection can affect pathogenic bacterial colonization and persistence in the mammalian intestine.

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Pancreaticobiliary factors in the modulation of small intestinal enterokinase in the rat

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1986.250.1.g103 ◽

1986 ◽

Vol 250 (1) ◽

pp. G103-G108 ◽

Cited By ~ 1

Author(s):

B. M. Newman ◽

P. C. Lee ◽

H. Tajiri ◽

D. R. Cooney ◽

E. Lebenthal

Keyword(s):

Small Intestine ◽

Bile Acids ◽

Common Duct ◽

Complete Loss ◽

Adult Rats ◽

Brush Border Enzymes ◽

Proximal Small Intestine ◽

Trophic Changes ◽

The Common ◽

Small Intestinal

Chronic pancreaticobiliary diversion was employed to study the modulation of enterokinase in the small intestine of adult rats. Diversion resulted in apparent trophic changes of the proximal bypassed portion of the intestinal mucosa. An almost complete loss of mucosal enterokinase activity in the proximal duodenum but no increase of enterokinase in the segments distal to reentry of the common duct was found in the pancreaticobiliary-diverted rats. The effect on the enterokinase activity in the proximal segment was specific in that no other brush-border enzymes measured in that segment were decreased. The decrease in enterokinase was partially prevented by dietary supplementation with pancreatic trypsinogen and completely avoided with the addition of a combination of bile acids and trypsinogen. Supplementation with bile acid alone did not preserve the enterokinase levels in the bypassed rats. The results suggested that trypsinogen is the primary factor responsible for modulating enterokinase levels in the proximal small intestine, with bile acids acting as a modifier.

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Helminth infection-induced changes to the small intestinal metabolome can promote helminth fecundity

10.26226/morressier.604a0a1f1a80aac83ca260c8 ◽

2021 ◽

Author(s):

Lisa Anne Reynolds

Keyword(s):

Helminth Infection ◽

Small Intestinal ◽

Induced Changes ◽

Helminth Fecundity

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A49 CO-INFECTION WITH PARASITIC WORMS ENHANCES THE ABILITY OF SALMONELLA TO COLONIZE THE GUT LUMEN AND DEWORMING RESTORES COLONIZATION RESISTANCE TO SALMONELLA

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwz047.048 ◽

2020 ◽

Vol 3 (Supplement_1) ◽

pp. 58-59

Author(s):

T P Brosschot ◽

K M Lawrence ◽

M H Kennedy ◽

R D FitzPatrick ◽

B E Moeller ◽

...

Keyword(s):

Small Intestine ◽

Bacterial Infection ◽

Helminth Infection ◽

Bacterial Pathogens ◽

Host Tissue ◽

Intestinal Colonization ◽

Wild Type ◽

Colonization Resistance ◽

Salmonella Infection ◽

Small Intestinal

Abstract Background Chronic infections with intestinal helminths occur primarily in world regions where infections with bacterial pathogens are also common. Research so far has shown that helminths can promote bacterial infection, however, the precise mechanisms of this are unknown. Current helminth control strategies involve mass deworming programs, and it is as yet unclear how deworming impacts susceptibility to bacterial infections in helminth-affected areas. Aims Our aims were to decipher the mechanistic details by which helminths can promote intestinal bacterial infection, and to determine how deworming affects susceptibility to intestinal colonization by bacterial pathogens. Methods Using a mouse model of enteric helminth-bacterial coinfection, we examined how the small intestinal helminth Heligmosomoides polygyrus promotes intestinal colonization by Salmonella enterica serovar Typhimurim. To study the effect of deworming of concurrent Salmonella infection, we treated our helminth-infected mice with the anthelmintic drug Strongid P both before and after Salmonella (co-) infection. To examine whether heightened Salmonella colonization during helminth infection depended on the ability of Salmonella to invade host tissue, we compared the ability of wild-type Salmonella or an invasion-deficient mutant (ΔinvA) to colonize during helminth co-infection. Results An ongoing helminth infection resulted in high levels of Salmonella in the small intestine after co-infection, however, when mice were dewormed prior to Salmonella co-infection, they were no longer susceptible to high small intestinal Salmonella burdens. In contrast, when helminth-infected mice are dewormed after Salmonella has already co-colonized, high Salmonella burdens persisted in the small intestine. Further, we found that during helminth co-infection, Salmonella primarily expands in the gut lumen rather than in the small intestinal tissue, and in line with this, a Salmonella invasion mutant was able to colonize the intestine to a similar extent to wild-type Salmonella during helminth infection. Conclusions Deworming experiments have revealed that the effects of H. polygyrus on promoting Salmonella colonization in the small intestines depend on the ongoing presence of the helminth. Deworming did not revert bacterial burdens once Salmonella had colonized, suggesting that an ongoing helminth infection reduces colonization resistance to Salmonella infection but was not required for Salmonella to persist after initial colonization by Salmonella. Further, we discovered that Salmonella expansion during helminth infection is independent of bacterial invasion of host tissue. Funding Agencies CIHR

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Infection with a small intestinal helminth Heligmosomoides polygyrus bakeri consistently alters microbial communities throughout the small and large intestine

10.1101/575787 ◽

2019 ◽

Author(s):

Alexis Rapin ◽

Audrey Chuat ◽

Luc Lebon ◽

Mario M. Zaiss ◽

Benjamin Marsland ◽

...

Keyword(s):

Microbial Communities ◽

Large Intestine ◽

Helminth Infection ◽

Entire Length ◽

Intestinal Helminth ◽

Mammalian Host ◽

Heligmosomoides Polygyrus ◽

Small Intestinal ◽

The Impact ◽

Small And Large Intestine

AbstractIncreasing evidence suggests that intestinal helminth infection can alter intestinal microbial communities with important impacts on the mammalian host. However, all of the studies to date utilize different techniques to study the microbiome and access different sites of the intestine with little consistency noted between studies. In the present study, we set out to perform a comprehensive analysis of the impact of intestinal helminth infection on the mammalian intestinal bacterial microbiome. For this purpose, we investigated the impact of experimental infection using the natural murine small intestinal helminth,Heligmosomoides polygyrus bakeri(Hpb) and examined possible alterations in both the mucous and luminal bacterial communities along the entire small and large intestine. We also explored the impact of common experimental variables, including the parasite batch and pre-infection microbiome, on the outcome of helminth-bacterial interactions. This work provides evidence that helminth infection reproducibly alters intestinal microbial communities – with an impact of infection noted along the entire length of the intestine. Although the exact nature of helminth-induced alterations to the intestinal microbiome differed depending on the parasite batch and microbiome community structure present prior to infection, changes extended well beyond the introduction of new bacterial species by the infecting larvae. Moreover, striking similarities between different experiments were noted, including the consistent outgrowth of a bacterium belonging to the Peptostreptococcaceae family throughout the intestine.Author SummaryIncreasing evidence indicates a role for interactions between intestinal helminths and the microbiome in regulating mammalian health, and a greater understanding of helminth-microbiota interactions may open the path for the development of novel immunomodulatory therapies. However, such studies are hampered by the inconsistent nature of the data reported so far. Such inconsistancies likely result from variations in the experimental and technological methodologies employed to investigate helminth-microbiota interactions and well has natural variation in the starting microbiome composition and/or worm genetics. We conducted a thorough study in which the reproducibility of helminth-induced alterations of microbial communities was determined and impact of common experimental variables – such as the starting microbiome and parasite batch - was determined. Our work reveals the robust ability of small intestinal helminth infection to alter microbial communities along the entire length of the intestine and additionally identifies a single bacterium that is strongly associated with infection across multiple experiments.

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The influence of a chronic subclinical infection ofTrichostrongylus colubriformison gastrointestinal motility and digesta flow in sheep

Parasitology ◽

10.1017/s0031182000057449 ◽

1985 ◽

Vol 91 (2) ◽

pp. 381-396 ◽

Cited By ~ 26

Author(s):

P. C. Gregory ◽

G. Wenham ◽

D. Poppi ◽

R. L. Coop ◽

J. C. MacRae ◽

...

Keyword(s):

Small Intestine ◽

Food Intake ◽

Transit Time ◽

Gastrointestinal Motility ◽

Subclinical Infection ◽

Intestinal Transit Time ◽

Small Intestinal Transit ◽

Proximal Small Intestine ◽

Small Intestinal ◽

Small Intestinal Transit Time

The influence of a chronic subclinicael infection ofTrichostrongylus colubriformis, 2500 larvae/day for 12 weeks, on gastrointestinal motility and digesta flow was studied in 12 sheep suppliedad libitumwith food and water. Motility was recorded by X-radiography and electromyography from chronically implanted electrodes;abomasal volume and outflow were estimated by dilution of CrEDTA; small intestinal transit time was estimated by passage of Phenol Red. The findings were compared with measurements made prior to infection at restricted food intake and reported separately. The first effects of infection were seen after 3–4 weeks. No animal developed diarrhoea, but food intake was progressively reduced. Small intestinal transit time, abomasal volume and half-time of marker dilution increased while abomasal outflow decreased during infection. These changes occurred both in absolute terms and when compared with values predicted from the observed level of food intake. As the animals became resistant to the parasites abomasal volume and digesta flow returned towards control values (weeks 10–12). The migrating myoelectric complex (MMC) was disrupted in only one sheep, and only transiently. In all sheep the frequency of the MMC was increased during infection and there was a progressive inhibition of abomasal, duodenal and jejunal motility. X-radiography showed there was prolonged pooling of digesta in the proximal small intestine which was cleared only at the phase of regular spiking activity. Two sheep given an anthelmintic drench recovered normal motility and clearance of digesta. It is concluded that subclinical infection of sheep with T.colubriformisalters the normal pattern of gastrointestinal motility in the absence of any diarrhoea, and causes inhibition of abomasal and proximal small intestinal motility and digesta flow. The increased frequency of MMCs helps to maintain digesta flow through the proximal small intestine.

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Branched Short-Chain Fatty Acid Isovaleric Acid Causes Colonic Smooth Muscle Relaxation via cAMP/PKA Pathway

Digestive Diseases and Sciences ◽

10.1007/s10620-018-5417-5 ◽

2018 ◽

Vol 64 (5) ◽

pp. 1171-1181 ◽

Cited By ~ 3

Author(s):

Bryan A. Blakeney ◽

Molly S. Crowe ◽

Sunila Mahavadi ◽

Karnam S. Murthy ◽

John R. Grider

Keyword(s):

Smooth Muscle ◽

Fatty Acid ◽

Short Chain Fatty Acid ◽

Muscle Relaxation ◽

Chain Fatty Acid ◽

Isovaleric Acid ◽

Short Chain ◽

Smooth Muscle Relaxation ◽

Pka Pathway

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Heligmosomoides, polygyrus, (syn. Nematospiroides, dubius), (Nematoda): distribution and net fluxes of glucose, H2O, Na+, K+, and Cl− in the mouse small intestine

Canadian Journal of Zoology ◽

10.1139/z84-008 ◽

1984 ◽

Vol 62 (1) ◽

pp. 37-40 ◽

Cited By ~ 5

Author(s):

M. V. K. Sukhdeo ◽

D. F. Mettrick

Keyword(s):

Small Intestine ◽

Water Flux ◽

Heligmosomoides Polygyrus ◽

Glucose Flux ◽

Proximal Small Intestine ◽

Normal Transmission ◽

And Migration ◽

Duodenal Lumen ◽

Net Fluxes

Mice were infected with 150 larvae of Heligmosomoides, polygyrus, and the effect of the worms on net fluxes of glucose, H2O, and electrolytes was followed from days 1–21 postinfection (PI) by means of an in vivo, perfusion technique. Maximum recovery of larvae was 77% at 5 days PI, and 64% for adults at 12 days PI following their emergence and migration into the duodenal lumen between days 7 and 9 PI. Inflammation decreased rapidly from day 9 PI onwards. Net glucose flux significantly decreased during the emergence of the adult worms (7–9 days PI). Water flux decreased and Na+ fluxes became negative at 5 days PI; Na+ and Cl− fluxes were negative at 7 days PI. Following the relocation of the adult worms in the proximal small intestine, fluxes returned to their normal levels. The differential changes in the net fluxes of glucose, H2O, and electrolytes suggest the secretion of a toxinlike substance by the parasites. In the normal mouse host, small infections have a temporary pathophysiological effect on the intestinal mucosa, differing significantly from previous studies using the abnormal rat host and large larval infections. As normal transmission of H. polygyrus, is by contamination, small infections, as employed in this study, probably reflect the natural condition.

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Mucosal Peptide Hydrolase and Brush-Border Marker Enzyme Activities in Three Regions of the Small Intestine of Rats with Experimental Uraemia

Clinical Science ◽

10.1042/cs0790663 ◽

1990 ◽

Vol 79 (6) ◽

pp. 663-668 ◽

Cited By ~ 6

Author(s):

D. J. Haines ◽

C. H. J. Swan ◽

J. R. B. Green ◽

J. F. Woodley

Keyword(s):

Enzyme Activity ◽

Small Intestine ◽

Intestinal Mucosa ◽

Brush Border ◽

Enzyme Activities ◽

Small Intestinal Mucosa ◽

Marker Enzyme ◽

Small Intestinal Transit ◽

Proximal Small Intestine ◽

Small Intestinal

1. The activities of nine peptide hydrolases and three non-peptidase brush-border marker enzymes have been quantified in crude homogenates prepared from the proximal, mid and distal regions of small-intestinal mucosa for sham-operated (n = 9) and uraemic (n = 14) rats. Abnormalities in enzyme activities were observed in all regions studied in the uraemic group, although no reduction in food intake occurred. 2. The proximal region of the small intestine from uraemic rats showed a general fall in enzyme activities associated with the brush-border. This fall was combined with a decline in mucosal protein content. In contrast, the mid and distal regions showed increased activity against the dipeptide tyrosyl-glycine. 3. It is proposed that the fall in brush-border enzyme activities in the proximal small intestine of uraemic rats is a response to the increased water intake associated with this, and presumably other, rat models of uraemia. The increased enzyme activity against tyrosyl-glycine found in the mid and distal regions of the small intestine of uraemic rats may be caused by an increased small-intestinal transit rate, but could be an attempt to maximize tyrosine absorption in response to decreased plasma tyrosine levels. 4. This study casts doubt on specific activities being the most useful units of enzyme activity, when measured in crude homogenates prepared from the proximal small intestine of uraemic rats. It also demonstrates that enzyme activities measured at a single site in the small intestine of uraemic rats may not be representative of the enzymatic changes occurring in the small-intestinal mucosa as a whole.

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