motilin and Inflammation

Cystic Fibrosis (CF) is a genetic condition characterized by neutrophilic inflammation and recurrent infection of the airways. How these processes are initiated and perpetuated in CF remains largely unknown. We have demonstrated a link between the intestinal microbiota-related metabolites bile acids (BA) and inflammation in the bronchoalveolar lavage fluid (BALF) from children with stable CF lung disease. To establish if BA indicate early pathological processes in CF lung disease, we combined targeted mass spectrometry and amplicon sequencing-based microbial characterization of 121 BALF specimens collected from 12-month old infants with CF enrolled in the COMBAT-CF study, a multicentre randomized placebo-controlled clinical trial comparing azithromycin versus placebo. We evaluated whether detection of BA in BALF is associated with the establishment of the inflammatory and microbial landscape of early CF lung disease, and whether azithromycin, a motilin agonist that has been demonstrated to reduce aspiration of gastric contents, alters the odds of detecting BA in BALF. We also explored how different prophylactic antibiotics regimens impact the early life BALF microbiota.. Detection of BA in BALF was strongly associated with biomarkers of airway inflammation, more exacerbation episodes during the first year of life, increased use of oral antibiotics with prolonged treatment periods, a higher degree of structural lung damage, and distinct microbial profiles. Treatment with azithromycin, a motilin agonist, which has been reported to reduce aspiration of gastric contents, did not reduce the odds of detecting BA in BALF. Culture and molecular methods showed that azithromycin does not alter bacterial load or diversity in BALF. Conversely, penicillin-type prophylaxis reduced the odds of detecting BAs in BALF, which was associated with elevated levels of circulating biomarkers of cholestasis. We also observed that environmental factors such as penicillin-type prophylaxis or BAs detection were linked to distinct early microbial communities of the CF airways, which were associated with different inflammatory landscapes but not with structural lung damage.. Detection of BA in BALF portend early pathological events in CF lung disease. Benefits early in life associated with azithromycin are not linked to its antimicrobial properties. Video Abstract.

Topics: Anti-Bacterial Agents; Azithromycin; Bile Acids and Salts; Bronchoalveolar Lavage Fluid; Cystic Fibrosis; Humans; Infant; Inflammation; Motilin; Penicillins

Gastrointestinal (GI) dysmotility in acute pancreatitis (AP) aggravates inflammation and results in severe complications. This study aimed to explore effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) on abdominal pain, GI dysmotility, and inflammation in AP patients.. Forty-two AP patients were blindly randomized to receive TEA (n = 21) at acupoints PC6 and ST36 or Sham-TEA (n = 21) at sham points for 2 days. Symptom scores, gastric slow waves, autonomic functions (assessed by spectral analysis of heart rate variability), circulatory levels of motilin, ghrelin, and TNF-α were measured before and after the treatment. Sixteen healthy controls (HCs) were also included without treatment for the assessment of gastric slow waves and biochemistry.. Compared with Sham-TEA, TEA decreased abdominal pain score (2.57 ± 1.78 vs. 1.33 ± 1.02, p < 0.05), bloating score (5.19 ± 1.21 vs. 0.76 ± 0.99, p < 0.001), the first defecation time (65.79 ± 19.51 h vs. 51.38 ± 17.19 h, p < 0.05); TEA, but not Sham-TEA, improved the percentage of normal gastric slow waves by 41.6% (p < 0.05), reduced AP severity score (5.52 ± 2.04 vs. 3.90 ± 1.90, p < 0.05) and serum TNF-α (7.59 ± 4.80 pg/ml vs. 4.68 ± 1.85 pg/ml, p < 0.05), and upregulated plasma ghrelin (0.85 ± 0.96 ng/ml vs. 2.00 ± 1.71 ng/ml, p = 0.001) but not motilin (33.08 ± 22.65 pg/ml vs. 24.12 ± 13.95 pg/ml, p > 0.05); TEA decreased sympathetic activity by 15.0% and increased vagal activity by 18.3% (both p < 0.05).. TEA at PC6 and ST36 administrated at early stage of AP reduces abdominal pain, improves GI motility, and inhibits inflammatory cytokine, TNF-α, probably mediated via the autonomic and ghrelin mechanisms.

Topics: Abdominal Pain; Acute Disease; Gastrointestinal Motility; Ghrelin; Humans; Inflammation; Motilin; Pancreatitis; Tumor Necrosis Factor-alpha

To verify the efficacy of electroacupuncture (EA) and acupoint injection on early postoperative intestinal obstruction and explore its mechanism.. One hundred and sixteen cases were divided randomly into two groups. In control group (56 cases), the conventional western medicine was applied, including gastrointestinal decompression, parenteral nutrition (PN), anti-inflammation and supporting therapy. In observation group (60 cases), on the basis of the treatment as control group, EA and acupoint injection with Neostigmine were supplemented. Zusanli (ST 36), Shangjuxu (ST 37)/Xiajuxu (ST 39) and Dachangshu (BL 25) were selected as main points. Before treatment and after 3 days treatment, the levels of plasma interleukint (IL-6), tumor necrosis factor-alpha (TNF-alpha) and motilin (MOT) were determined.. In observation group, the mean recovery time of bowel sound and the mean frequency of passing gas were less than those in control group (both P < 0.01). After treatment, in either group, the levels of IL-6 and TNF-alpha were down-regulated as compared with those before treatment (all P < 0.01). After treatment, in observation group, IL-6 level was (15.2 +/- 4.1) pg/mL and TNF-alpha level was (18.3 +/- 6.5) pg/mL. They were (35.5 +/- 7.2) pg/mL and (52.7 +/- 12.3) pg/mL respectively in control group, indicating significant difference in statistics between two groups (both P < 0.01). In either group, MOT level increased after treatment as compared with that before treatment (both P < 0 01). After treatment, in observation group, the increase of MOT level was superior to that in control group [(190.7 +/- 48. 5 ) pg/mL vs (114.6 +/- 36.9) pg/mL, P < 0.01].. Electroacupuncture and acupoint injection are significantly effective in the treatment of early postoperative intestinal obstruction. This therapy may inhibit the release of inflammatory factors to reduce intestinal wall edema and it may promote MOT secretion to increase intestinal peristalsis. As a result, the recovery of gastrointestinal function is promoted.

Topics: Acupuncture Points; Adult; Aged; Cytokines; Electroacupuncture; Female; Humans; Inflammation; Injections; Intestinal Obstruction; Male; Middle Aged; Motilin; Postoperative Complications

Altered concentrations of ghrelin, motilin, and cholecystokinin (CCK) may contribute to gastric hypomotility. The aims of this study were to evaluate the concentrations of these hormones in patients tolerant and intolerant to gastric nutrition, assess the influence of prokinetic therapy on these hormone concentrations, determine the associations between these mediators and gastric emptying, and evaluate whether inflammation influences their concentrations.. Post hoc analyses of 2 prospective studies that enrolled 20 critically ill patients with an aspirated gastric residual (GR) >150 mL while receiving gastric enteral nutrition (intolerant group) and 10 critically ill patients with minimal GR (tolerant group). Patients with intolerance were also assessed 1 day after prokinetic therapy. Fasting serum concentrations of total ghrelin, acyl ghrelin (active), des-acyl ghrelin (inactive), motilin, CCK, and tumor necrosis factor (TNF)-α were determined. Gastric emptying was assessed concurrently using the acetaminophen absorption method.. Compared to the tolerant group, the intolerant group had higher total ghrelin (1324.8 ± 1204.6 vs 285.1 ± 132.5 pg/mL; P < .001), lower acyl ghrelin (70.5 ± 65.4 vs 208.5 ± 186.9 pg/mL; P < .05), and lower acyl ghrelin to des-acyl ghrelin ratio (1.11 ± 1.35 vs 3.47 ± 3.21 pg/mL; P < .05). Concentrations of other hormones and TNF-α were similar. Despite accelerated gastric emptying after prokinetic therapy, concentrations of all hormones and TNF-α were similar to baseline values. Hormone concentrations were not associated with gastric emptying or TNF-α.. Patients intolerant to gastric nutrition generate less acyl ghrelin, which may contribute to gastric hypomotility. Intolerance is not associated with altered concentrations of other hormones. Hormone concentrations are not influenced by prokinetic therapy.

Topics: Adult; Aged; Cholecystokinin; Critical Illness; Enteral Nutrition; Female; Gastric Emptying; Gastrointestinal Hormones; Ghrelin; Humans; Inflammation; Male; Middle Aged; Motilin; Prospective Studies; Respiratory Aspiration; Stomach Diseases; Tumor Necrosis Factor-alpha

The aim of the study was to determine the clinical significance of intestinal functional and structural alterations in biliary pathology. Clinical, endoscopic, morphological, and morphometric methods were used. The subjects of the study were 62 patients with functional gall bladder disorder, 90 patients with chronic calculous cholecystitis, and 90 patients who had undergone cholecystectomy for cholelithiasis. The study found that biliary lithogenesis was associated with intestinal dysbiosis, changes in the qualitative density of erythrocytes immunopositive to motilin and substance P, and inflammatory changes in the intestines. After cholecystectomy, changes in intestinal microecology progressed, inflammatory and atrophic changes in the intestinal mucosa appeared or deepened, the qualitative density of erythrocytes immunopositive to motilin and substance P decreased, and colon polyps appeared more frequently.

Topics: Adult; Aged; Atrophy; Cholecystitis; Cholelithiasis; Chronic Disease; Colonic Polyps; Diagnosis, Differential; Erythrocyte Count; Erythrocytes; Female; Humans; Inflammation; Intestinal Mucosa; Male; Middle Aged; Motilin; Predictive Value of Tests; Prognosis; Substance P

Bacillary dysentery arises when Shigella invades the colonic and rectal mucosae of the human gut and elicits a strong inflammatory response, which may lead to life-threatening complications. Hence, downregulation of the host inflammatory response is an appealing therapeutical alternative. The gastrointestinal tract is densely innervated, and nerve endings are often found in the vicinity of leukocytes. We have assessed the impact of experimental Shigella infection on levels of neuropeptides in the intestinal mucosa of rabbits. Ligated small intestinal loops were created in rabbits, and either live, pathogenic Shigella flexneri, a nonpathogenic mutant of Shigella, or NaCl was injected into the loops. Infection was allowed to proceed for 8 or 16 h, after which the rabbits were sacrificed and intestinal biopsies collected. Tissue destruction, fluid secretion and degree of bacterial invasion were monitored. Intestinal biopsies were homogenized, and levels of the neuropeptides calcitonin gene-related peptide, substance P, peptide YY (PYY), vasoactive intestinal peptide, somatostatin, galanin, motilin and neurotensin were measured by radioimmunoassay. Loops exposed to invasive Shigella had 5.7 times lower levels of PYY (P = 0.0095) than loops exposed to NaCl, after 16 h of infection. The levels of the other neuropeptides tested were unchanged. Inhibition of nicotinic cholinergic neurotransmission partly protected the intestinal mucosa from destruction elicited by invasive Shigella. These findings indicate that a tissue-invasive bacterium such as Shigella, which is strictly localized to the intestinal mucosa, activates intramural nerve reflexes that presumably involve a nicotinic synapse as well as the neuropeptide PYY.

Topics: Animals; Calcitonin Gene-Related Peptide; Dysentery, Bacillary; Galanin; Hexamethonium; Inflammation; Intestinal Mucosa; Intestine, Small; Motilin; Neuropeptides; Neurotensin; Nicotinic Antagonists; Peptide YY; Rabbits; Shigella flexneri; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Treatment with the anti-inflammatory cytokine, interleukin-11 (IL-11), in rabbits with TNBS-colitis reduces tissue damage but does not normalize body weight loss despite an increase in plasma levels of motilin, known to stimulate food intake. We investigated whether IL-11 could increase plasma levels of the anorectic peptide, leptin in non-inflamed and inflamed rabbits. In addition, the effect of IL-11 and leptin on motilin mRNA expression in the T84 cell line was tested. Five days post-inflammation, weight loss amounted 10.7+/-1.2%, but plasma leptin and motilin levels were unaffected. During IL-11 treatment, weight loss remained and plasma leptin levels dose-dependently increased with 27+/-5% (4 microg/kg day) and 108+/-7% (720 microg/kg day). Motilin levels increased in parallel with 23+/-12% or 256+/-97%. In non-inflamed animals, a prompt decrease in weight (-11.9+/-1%) was observed after treatment with the highest dose of IL-11 and this was associated with an increase in plasma leptin (70+/-18%) and motilin levels (113+/-7%). Both IL-11 and leptin stimulated motilin mRNA expression in T84 cells with a different time profile. In conclusion, the increase in plasma leptin levels during IL-11 treatment induces wasting in normal rabbits and may be one of the major factors involved in the maintenance of body weight loss in rabbits with colitis. Increase of motilin expression by leptin may be part of a feedback mechanism.

Topics: Animals; Cell Line; Colitis; Gene Expression Regulation; Inflammation; Interleukin-11; Leptin; Motilin; Rabbits; RNA, Messenger; Weight Loss

A number of human diseases with intestinal adaptation have been investigated, including acute infective diarrhoea, intestinal resection, jejuno-ileal bypass, coeliac disease, tropical sprue, chronic pancreatitis and cystic fibrosis. In all, the newly isolated hormone enteroglucagon appeared to be elevated in proportion to the degree of adaptation. In rats after gut resection and cold adaptation, enteroglucagon was also elevated and the degree of elevation correlated closely with the crypt cell production rate (CCPR). Chronic administration of somatostatin suppressed both enteroglucagon and CCPR, while bombesin stimulated both. A crude preparation of enteroglucagon was found to directly stimulate DNA synthesis in enterocyte cultures. It is thus concluded that, at present, the most likely candidate for the humoral component of intestinal adaptation is the hormonal peptide enteroglucagon.

Topics: Adaptation, Physiological; Adult; Animals; Cattle; Diarrhea; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Hypertrophy; Infant; Inflammation; Intestinal Diseases; Intestinal Mucosa; Intestine, Small; Intestines; Mice; Motilin; Obesity; Rats