Role of gut-brain axis in persistent abnormal feeding behavior in mice following eradication of Helicobacter pylori infection

Bacterial infection can trigger the development of functional GI disease. Here, we investigate the role of the gut-brain axis in gastric dysfunction during and after chronic H. pylori infection. Control and chronically H. pylori-infected Balb/c mice were studied before and 2 mo after bacterial eradication. Gastric motility and emptying were investigated using videofluoroscopy image analysis. Gastric mechanical viscerosensitivity was assessed by cardioautonomic responses to distension. Feeding patterns were recorded by a computer-assisted system. Plasma leptin, ghrelin, and CCK levels were measured using ELISA. IL-1β, TNF-α, proopiomelanocortin (POMC), and neuropeptide Y mRNAs were assessed by in situ hybridizations on frozen brain sections. Gastric inflammation was assessed by histology and immunohistochemistry. As shown previously, H. pylori-infected mice ate more frequently than controls but consumed less food per bout, maintaining normal body weight. Abnormal feeding behavior was accompanied by elevated plasma ghrelin and postprandial CCK, higher TNF-α (median eminence), and lower POMC (arcuate nucleus) mRNA. Infected mice displayed delayed gastric emptying and visceral hypersensitivity. Eradication therapy normalized gastric emptying and improved gastric sensitivity but had no effect on eating behavior. This was accompanied by persistently increased TNF-α in the brain and gastric CD3+ T-cell counts. In conclusion, chronic H. pylori infection in mice alters gastric emptying and mechanosensitivity, which improve after bacterial eradication. A feeding pattern reminiscent of early satiety persists after H. pylori eradication and is accompanied by increased TNF-α in the brain. The results support a role for altered gut-brain pathways in the maintenance of postinfective gut dysfunction.

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Distribution of leukocyte subpopulation among students threatened by failure

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i3.2553 ◽

2020 ◽

Vol 11 (3) ◽

pp. 3807-3812

Author(s):

Aziez Chettoum ◽

Kamilia Guedri ◽

Zouhir Djerrou ◽

Rachid Mosbah ◽

Latifa Khattabi ◽

...

Keyword(s):

Immune System ◽

White Blood Cells ◽

Significant Development ◽

Biological Assays ◽

Cell Counts ◽

Student Volunteers ◽

White Blood Cell Counts ◽

Academic Year ◽

The Brain

Psychoneuroimmunology or the study of the relationships between the brain and the immune system is an area of research that has experienced significant development over the decade. Stress does not appear without consequences on the state of health, the role of fears, emotions and significant constraints in the appearance of organic and mental diseases. In this research, we studied the effect of stress and anxiety during exams at the end of the academic year (2018/2019) on the distribution of leukocyte subpopulations and the immune system, questionnaires has been completed by student volunteers, to estimate the anxio-depressive comorbidities through the (HADS) test during and outside exams, and in the same time we asked them for a blood sample the next morning day to carry out some biological assays (CBC). We also found that stress during exams caused a change in the distribution of different types of white blood cells, a total decrease in white blood cell counts with neutropenia and lymphopenia were found in students during exams compared to controls, and an increase in monocyte and other types of polymorphonuclear levels in students during exams compared to controls. Other tests measuring the effects of stress on specific functions of the immune system can be used.

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Effects of Joint Lavage with Dimethylsulfoxide on LPS-Induced Synovitis in Horses—Clinical and Laboratorial Aspects

Veterinary Sciences ◽

10.3390/vetsci7020057 ◽

2020 ◽

Vol 7 (2) ◽

pp. 57

Author(s):

Eric Danilo Pauls Sotelo ◽

Cynthia Prado Vendruscolo ◽

Joice Fülber ◽

Sarah Raphaela Torquato Seidel ◽

Fernando Mosquera Jaramillo ◽

...

Keyword(s):

Synovial Fluid ◽

Cartilage Degradation ◽

Cell Counts ◽

Tnf Α ◽

Equine Medicine ◽

Lactated Ringer's Solution ◽

White Blood Cell Counts ◽

Factor Α ◽

Joint Lavage

Several studies in human and equine medicine have produced controversial results regarding the role of dimethylsulfoxide (DMSO) as a therapeutic agent. This study aimed to evaluate the effect of joint lavage with different DMSO concentrations on biomarkers of synovial fluid inflammation and cartilage degradation in joints with lipopolysaccharide (LPS)-induced synovitis. Twenty-six tibiotarsal joints of 13 horses were randomly distributed into four groups (lactated Ringer’s solution; 5% DMSO in lactated Ringer’s; 10% DMSO in lactated Ringer’s; and sham). All animals were evaluated for the presence of lameness, and synovial fluid analyses were performed at 0 h, 1 h, 8 h, 24 h, and 48 h (T0, T1, T8, T24, and T48, respectively). The white blood cell counts (WBC), total protein (TP), urea, prostaglandin E2 (PGE2), interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-α (TNF-α), hyaluronic acid (HA), and chondroitin sulfate (CS) concentrations were measured. The WBC counts and PGE2, IL-1β, IL-6, and TP concentrations increased in all groups at T8 compared to baseline values (p < 0.05). At T48, only the 5% DMSO and 10% DMSO groups showed a significant decrease in WBC counts (p < 0.05). Furthermore, the 10% DMSO group had lower concentrations of PGE2 and IL-1β at T48 than at T8 (p < 0.05) and presented lower IL-6 levels than the5% DMSO and lactated Ringer’s groups at T24. All groups showed an increase in CS concentration after LPS-induced synovitis. Joint lavage with 10% DMSO in lactated Ringer’s has anti-inflammatory but not chondroprotective effects.

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Relationship Between Mucosal TNF-α Expression and Th1, Th17, Th22 and Treg Responses in Helicobacter Pylori Infection

10.21203/rs.3.rs-251809/v1 ◽

2021 ◽

Author(s):

Ghorbanali Rahimian ◽

Milad Shahini Shams Abadi ◽

Reza Ahmadi ◽

Mohammedhadi Shafigh ◽

Fatemeh Azadegan-Dehkordi

Keyword(s):

Helicobacter Pylori ◽

Gastric Mucosa ◽

Treg Cells ◽

Infected Group ◽

Ulcer Disease ◽

Tnf Α ◽

H Pylori ◽

Factor Α ◽

Necrosis Factor

Abstract Background: Helicobacter pylori (H. pylori) -induced gastric inflammation in the gastric mucosa and significantly increases the risk of developing gastritis and peptic ulcer disease (PUD). The objective of this research is to determine the role of tumor necrosis factor-α (TNF-α) expression in the gastric mucosa of patients with H. pylori –associated gastritis and PUD compared to uninfected patients, and we determined the relation between TNF-α expression and Th1/Th17/Th22, and Treg cells.Methods: Fifty-five patients with H. pylori –associated gastritis, 47 patients with H. pylori –associated PUD, and 48 uninfected patients were in this research. Antrum biopsy was used to detect H. pylori, virulence factors and histopathological assessments.Results: Expression of TNF-α in the infected group was significantly higher than the uninfected group. Also, cagA/oipA-positive infected patients induce significantly more TNF-α expression than do cagA/oipA-negative infected patients. Expression of TNF-α was significantly increased in the PUD group than the gastritis group. Notably, TNF-α expression had a significant positive correlation with the frequency of Th1/Th17/Th22 lymphocytes in the PUD group.Conclusion: These findings indicate the importance of increasing TNF-α with Th1, Th17, Th22 responses increase as an important risk factor for PUD in context of H. pylori infection.

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Symptoms in functional dyspepsia: Role of H. pylori infection and delayed gastric emptying

Gastroenterology ◽

10.1016/s0016-5085(98)83346-5 ◽

1998 ◽

Vol 114 ◽

pp. A821

Author(s):

F. Perri ◽

R. Clemente ◽

V. Festa ◽

M. Quitadamo ◽

V. Annese ◽

...

Keyword(s):

Gastric Emptying ◽

Functional Dyspepsia ◽

Delayed Gastric Emptying ◽

H Pylori

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The effects of 6 hours of hypoxia on protein synthesis in rat tissues in vivo and in vitro

Biochemical Journal ◽

10.1042/bj2280179 ◽

1985 ◽

Vol 228 (1) ◽

pp. 179-185 ◽

Cited By ~ 58

Author(s):

V R Preedy ◽

D M Smith ◽

P H Sugden

Keyword(s):

Protein Synthesis ◽

Gastric Emptying ◽

Skeletal Muscles ◽

Rat Tissues ◽

Tissue Nitrogen ◽

The Brain ◽

H Protein

Rates of protein synthesis were measured in vivo in several tissues (heart, skeletal muscles, liver, tibia, skin, brain, kidney, lung) of fed rats exposed to O2/N2 (1:9) for 6 h starting at 08:00-11:00 h. Protein synthesis rates were depressed by 15-35% compared with normoxic controls in all of the tissues studied. The decreases were greatest in the brain and the skin. Although hypoxia inhibited gastric emptying, its effects on protein synthesis could probably not be attributed to its induction of a starved state, because protein-synthesis rates in brain and skin were not decreased by a 15-18 h period of starvation initiated at 23:00 h. Furthermore, we showed that protein synthesis was inhibited by hypoxia in the rat heart perfused in vitro, suggesting a direct effect. The role of hypoxia in perturbing tissue nitrogen balance in various physiological and pathological states is discussed.

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Elucidating the role of leptin in systemic inflammation: a study targeting physiological leptin levels in rats and their macrophages

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00171.2017 ◽

2017 ◽

Vol 313 (5) ◽

pp. R572-R582 ◽

Cited By ~ 9

Author(s):

Elizabeth A. Flatow ◽

Evilin N. Komegae ◽

Monique T. Fonseca ◽

Camila F. Brito ◽

Florin M. Musteata ◽

...

Keyword(s):

Food Deprivation ◽

Systemic Inflammation ◽

Peritoneal Macrophages ◽

Tnf Α ◽

Macrophage Subpopulations ◽

Limited Food ◽

The Brain

To elucidate the role of leptin in acute systemic inflammation, we investigated how its infusion at low, physiologically relevant doses affects the responses to bacterial lipopolysaccharide (LPS) in rats subjected to 24 h of food deprivation. Leptin was infused subcutaneously (0–20 μg·kg−1·h−1) or intracerebroventricularly (0–1 μg·kg−1·h−1). Using hypothermia and hypotension as biomarkers of systemic inflammation, we identified the phase extending from 90 to 240 min post-LPS as the most susceptible to modulation by leptin. In this phase, leptin suppressed the rise in plasma TNF-α and accelerated the recoveries from hypothermia and hypotension. Suppression of TNF-α was not accompanied by changes in other cytokines or prostaglandins. Leptin suppressed TNF-α when infused peripherally but not when infused into the brain. Importantly, the leptin dose that suppressed TNF-α corresponded to the lowest dose that limited food consumption; this dose elevated plasma leptin within the physiological range (to 5.9 ng/ml). We then conducted in vitro experiments to investigate whether an action of leptin on macrophages could parallel our in vivo observations. The results revealed that, when sensitized by food deprivation, LPS-stimulated peritoneal macrophages can be inhibited by leptin at concentrations that are lower than those reported to promote cytokine release. It is concluded that physiological levels of leptin do not exert a proinflammatory effect but rather an anti-inflammatory effect involving selective suppression of TNF-α via an action outside the brain. The mechanism of this effect might involve a previously unrecognized, suppressive action of leptin on macrophage subpopulations sensitized by food deprivation, but future studies are warranted.

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Gastric accommodation in non-ulcer dyspepsia and the roles ofHelicobacter pylori infection and vagal function

Gut ◽

10.1136/gut.44.1.55 ◽

1999 ◽

Vol 44 (1) ◽

pp. 55-64 ◽

Cited By ~ 108

Author(s):

M Thumshirn ◽

M Camilleri ◽

S B Saslow ◽

D E Williams ◽

D D Burton ◽

...

Keyword(s):

Gastric Emptying ◽

Minnesota Multiphasic Personality Inventory ◽

Cold Water ◽

Gastrointestinal Symptoms ◽

Therapeutic Approaches ◽

Gastric Accommodation ◽

Gastric Sensitivity ◽

Non Ulcer Dyspepsia ◽

H Pylori ◽

Vagal Function

BackgroundThe pathophysiological mechanisms in non-ulcer dyspepsia are incompletely understood.AimsTo compare gastric motor and sensory functions in Helicobacter pyloripositive or negative patients with non-ulcer dyspepsia.PatientsSeventeen patients with non-ulcer dyspepsia and 16 asymptomatic controls.MethodsThe following were evaluated: gastrointestinal symptoms; gastric emptying and orocaecal transit of solids; abdominal vagal function; gastric compliance; fasting and postprandial gastric tone and phasic contractions; symptoms during ingestion of cold water and during the distension of an intragastric bag; and somatic sensitivity and personality profile (Minnesota Multiphasic Personality Inventory, MMPI).ResultsGastric accommodation was reduced in H pylori negative dyspeptics relative to controls; the degree of accommodation was unrelated toH pylori status in dyspeptics. Increased postprandial gastric sensation was more frequent amongH pylori positive patients (4/5H pylori positive versus 4/12H pylori negative patients). Intragastric meal distribution and orocaecal transit were normal; gastric emptying at four hours was abnormal in 4/17 patients. Vagal dysfunction was rare. Eight of 17 patients had somatisation or depression on MMPI.ConclusionImpaired gastric accommodation is frequent in non-ulcer dyspepsia and seems to be unrelated to vagal efferent dysfunction. H pylori infection does not seem to influence gastric accommodation, but is associated with heightened sensitivity in dyspeptics. Therapeutic approaches that restore normal postprandial accommodation and gastric sensitivity should be tested in non-ulcer dyspepsia.

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Helicobacter pylori-secreted factors inhibit dendritic cell IL-12 secretion: a mechanism of ineffective host defense

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00139.2005 ◽

2006 ◽

Vol 291 (1) ◽

pp. G73-G81 ◽

Cited By ~ 57

Author(s):

John Y. Kao ◽

Sivaprakash Rathinavelu ◽

Kathryn A. Eaton ◽

Longchuan Bai ◽

Yana Zavros ◽

...

Keyword(s):

Helicobacter Pylori ◽

Dendritic Cells ◽

Bacterial Colonization ◽

Stable Factor ◽

Heat Stable ◽

Tnf Α ◽

Intestinal Pathogens ◽

H Pylori

Helicobacter pylori evades host immune defenses and causes chronic gastritis. Immunity against intestinal pathogens is largely mediated by dendritic cells, yet the role of dendritic cells in acute H. pylori infection is largely unknown. We observed the recruitment of dendritic cells to the gastric mucosa of H. pylori-infected mice. Bone marrow-derived dendritic cells from mice responded to live H. pylori by upregulating the expression of proinflammatory cytokine mRNA (i.e., IL-1α, IL-1β, and IL-6). The supernatant from dendritic cells stimulated with H. pylori for 18 h contained twofold higher levels of IL-12p70 than IL-10 and induced the proliferation of syngeneic splenocytes and type 1 T helper cell cytokine release (IFN-γ and TNF-α). These responses were significantly lower compared with those induced by Acinetobacter lwoffi, another gastritis-causing pathogen more susceptible to host defenses. Analysis of whole H. pylori sonicate revealed the presence of a heat-stable factor secreted from H. pylori that specifically inhibited IL-12 but not IL-10 release from dendritic cells activated by A. lwoffi. Our findings suggest that dendritic cells participate in the host immune response against H. pylori and that their suppression by H. pylori may explain why infected hosts fail to prevent bacterial colonization.

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Gastric branch vagotomy blocks nutrient and cholecystokinin-induced suppression of gastric emptying

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1993.264.3.r630 ◽

1993 ◽

Vol 264 (3) ◽

pp. R630-R637 ◽

Cited By ~ 16

Author(s):

G. J. Schwartz ◽

G. Berkow ◽

P. R. McHugh ◽

T. H. Moran

Keyword(s):

Gastric Emptying ◽

Intraperitoneal Administration ◽

Physiological Saline ◽

Male Rats ◽

Caloric Content ◽

Vagus Nerves ◽

Acidic Solutions ◽

Caloric Density ◽

The Brain

A role for the vagus nerve in the emptying of intragastric nutrients and the gastric inhibitory actions of the brain-gut peptide cholecystokinin (CCK) has been proposed. To directly assess the role of the gastric vagal branches in these actions, we compared the emptying of 5-ml nutrient and nonnutrient gastric loads in male rats in which both branches of the gastric vagus nerves were cut (GVX, n = 7) with emptying in surgical control (n = 8) rats. Gastric emptying of saline was also examined in both groups after intraperitoneal administration of 8 micrograms/kg CCK. In control rats, high osmolarity, low pH, and caloric density all significantly decreased gastric emptying compared with the emptying of physiological saline. In addition, fat (oleic acid) and protein (peptone) loads emptied significantly more slowly than isocaloric carbohydrate (glucose) loads. Gastric branch vagotomy completely blocked the suppression of emptying produced by fat, protein, carbohydrate, and acid loads. In addition, GVX attenuated the ability of hyperosmotic nutrient and nonnutrient loads to inhibit emptying to the same degree, irrespective of their caloric content. Finally, in intact rats, CCK significantly inhibited the emptying of physiological saline, and gastric vagotomy abolished this suppression. Taken together, these results are consistent with the proposals that 1) the controlled emptying of caloric, hyperosmotic, and acidic solutions is dependent on gastric vagal branches, and 2) exogenous CCK relies on an intact vagal pathway in the control of gastric emptying.

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