Influence of oral intake of seven different antibiotics on faecal short-chain fatty acid excretion in healthy subjects

Faecal excretion of short-chain fatty acids (SCFAs) has been measured by gas chromatography in groups of six or seven healthy subjects before, during, and after they received the antibiotics bacitracin, co-trimoxazol, doxycycline, erythromycin, nalidixic acid, ofloxazin, or vancomycin orally for 6 days. Intake of bacitracin and vancomycin had pronounced effects on faecal SCFAs excretion and reduced median total concentration of SCFAs from 105.4 mmol/kg to 21.8 mmol/kg and from 69.3 mmol/kg to 19.4 mmol/kg, respectively (p less than 0.05). Erythromycin had moderate effects on the faecal SCFAs excretion, whereas small or no changes were seen during intake of co-trimoxazol, doxycycline, nalidixic acid, and ofloxacin. 2-Methylbutyric acid, a SCFA not previously seen in human faeces, was found in the faeces of all subjects (median concentration before intake of antibiotic, 1.3 mmol/kg). Bacitracin, erythromycin, nalidixic acid, and vancomycin were detected in high concentrations in faeces during therapy, whereas trimethoprim, doxycycline, and ofloxacin were found in relatively low concentrations. In conclusion, some, but not all, peroral antimicrobials induce changes in faecal SCFAs, most likely reflecting changes in the colonic ecosystem.     

Influence of antibiotics on the faecal excretion of bile pigments in healthy subjects

We have evaluated the effects of 10 antibiotics, given orally for 6 days to healthy subjects, on faecal excretion of urobilinogen. Intake of bacitracin, vancomycin, clindamycin, erythromycin, and ampicillin resulted in a pronounced suppression of the faecal excretion of urobilinogen (p less than 0.05). Intake of doxycycline, metronidazole, nalidixic acid, ofloxacin, and trimethoprim/sulphamethoxazole had no significant effect. The effects of three antibiotics-ampicillin, clindamycin, and metronidazole--on faecal excretion of conjugated bilirubin were similarly evaluated. Intake of clindamycin led to a marked increase of conjugated bilirubin (p less than 0.05) in the faeces, and the pattern of separated azopigment derivatives of the bilirubin conjugates became altered. Intake of ampicillin and metronidazole resulted in far less alterations in faecal conjugated bilirubin, although a significant change was observed in the subjects receiving metronidazole (p less than 0.05). The differences between the antibiotics with regard to altered intestinal bile pigment metabolism may be due to differences in antimicrobial spectra and/or intestinal concentrations of the drugs. Our findings indicate that orally taken antibiotics may cause a suppression of the microbial deconjugation of conjugated bilirubin and urobilinogen formation, respectively. This may reflect a pronounced disturbance of the intestinal microflora.     

Influence of short-chain fatty acids on iron absorption by proximal colon

BACKGROUND: Short-chain fatty acids produced by bacterial fermentation in the colon enhance the local absorption of cations, such as calcium, that could be used to improve the bioavailability of iron if a significant colonic absorption of iron were to occur. METHODS: Iron (iron gluconate, 100 microM) absorption by the caecum of the rat was compared with that in proximal sites of the small bowel using the Ussing chamber model; the influence of probiotic bacteria (Propionibacterium freudenreichii) on iron absorption was assessed and compared with that of two of their fermentation products (acetic and propionic acids) using the Ussing chamber and the ligated colon with gamma emitting iron as experimental models. RESULTS: The caecum absorbed less iron than the duodenum, but significantly more than the jejunum and ileum. This occurred mainly through an enhanced mucosal transfer of iron uptake. Propionibacteria enhanced iron absorption from the proximal colon; the same effect was observed in the presence of viable bacteria, or the culture medium free of viable bacteria, or acetate and propionate or propionate alone. CONCLUSIONS: The proximal colon could be a significant site available for iron absorption; this absorption can be enhanced by local production of short-chain fatty acids such as propionate.     

Influence of dietary habits,age and gender on plasma fatty acids levels in a population of healthy Tunisian subjects

The fatty acids composition of circulating blood lipids is expected to be altered by many factors (ageing, dietary intake, lifestyle...). In addition to the ageing consequences on their lipid status, elderly subjects represent a population at risk of nutritional imbalance. The main objective of the present study was to investigate the associations between dietary habits and the plasma fatty acids patterns in a healthy Tunisian population with an emphasis on the gender and ageing differences for the ?6-desaturase activity and the EFA proportions. Nutritional habits and plasma fatty acids compositions have been therefore evaluated in 200 healthy volunteers (104 women and 96 men) aged between 40 and 82 years old. The findings revealed that the ?6-desaturase activity was reduced in elderly subjects (by 24% and 10% in women and men respectively). Moreover, DHA (C22:6n−3) and AA (C20:4n−6) were found to increase respectively in high fish and meat consumers. Plasma fatty acids composition could be sensitive to dietary habits according to particular food items and should then help for the establishment of optimal nutritional proportions.     

Influence of fiber on postprandial intragastric juice acidity, pepsin, and bile acids in healthy subjects

The effect of a fiber-enriched wheat bran product, Fiberform, and a guar gum preparation, Guarem, on postprandial intragastric juice acidity and pepsin and bile acid concentrations was studied in healthy subjects. Fiber-enriched wheat bran prolonged significantly the meal-induced elevation of pH and decrease in pepsin. Both fiber products reduced postprandial intragastric bile acid concentration.     

短链脂肪酸在肠道中的生理作用

越来越多的证据显示,短链脂肪酸对肠道的能量供应、肠黏膜屏障的维持、肠道高敏感和肠道动力的调节、免疫调节及抗肿瘤效应等有重要作用。进一步明确短链脂肪酸的生理作用及其与肠道相关疾病的关联及其内在机制,对肠道疾病的预防与治疗有重要意义。该文就短链脂肪酸在肠道中的生理作用作一综述。     

Treatment of diversion colitis by short-chain fatty acids

Diminished production of short-chain fatty acids (SCFA) by altered flora has been suggested in the pathogenesis of diversion colitis (DC). We evaluated prospectively the effectiveness of SCFA irrigation in 13 patients with excluded colon (eight males, five females; mean age, 48 years). The causes of diversion were inflammatory bowel disease (n=4), colonic cancer (n=2), sigmoid diverticulitis with perforation (n=3), ischiorectal abscess (n=2), and miscellaneous (n=2). Patients were given, twice a day for 14 days in a double-blind manner, a 60-ml enema containing either SCFA (acetate: 60 mmol/liter; proprionate: 30 mmol/liter; and N-butyrate: 40 mmol/ liter) (Group 1; n=7) or isotonic NaCl (Group 2; n=6). Endoscopy with biopsies was performed before starting the trial (D1) and 14 days later (D14). On D1 all patients had endoscopic and histologic findings suggestive of DC. No endoscopic or histologic changes were observed on D14 in either group. We conclude that endoscopic and histologic lesions of DC were not improved by SCFA irrigation during the 14 days.A preliminary communication of this work was abstracted in Gut 1989;30:1470 and read at the meeting of the British Society of Gastroenterology, Dublin, Ireland, September 1989.     

Absorption of short-chain fatty acids by the colon

Short-chain fatty acids (SCFAs) constitute the major solute fraction of normal stool water and are responsible for the diarrhea associated with carbohydrate (CHO) malabsorption. Although SCFA absorption from the human small bowel has been reported previously, the fate of SCFAs in the colon--their major site of production--was investigated in the present study. The colon of normal volunteers was perfused with neutral, isotonic solutions containing SCFA, 0-90 mM. Propionate was studied in detail with limited observations on acetate and n-butyrate. SCFA absorption was concentration-dependent; back diffusion of metabolic products, ketone bodies, was quantitatively insignificant. The transport process was accompanied by increased Na, K, and water absorption, by luminal alkalinization due to bicarbonate accumulation, and by a fall in lumen PCO2. The results are consistent with the existence of two mechanisms for colonic SCFA absorption: first, nonionic diffusion of protonated SCFA involving consumption of luminal CO2; this process accounts for about 60% of total SCFA absorption; and second, cellular uptake by ionic diffusion of the Na or K salt of the SCFA.     

Stimulation of ileal emptying by short-chain fatty acids

We have shown previously that short-chain fatty acids (mixtures of acetic, propionic, and butyric acids; SCFAs) in the proportions found usually in stool water stimulate fasting ileal motility. Based on indirect evidence, we proposed that these motor patterns (bursts of phasic pressure waves that were propagated) would be propulsive, but the capacity of these stimulated patterns of motility to propel contents has not been established directly. Healthy, surviving dogs were provided with motility sensors and a cannula through which SCFAs could be instilled into the ileum. Boluses of SCFAs were much more likely to stimulate phasic bursts of motility than was saline. Scintigraphic studies using a gamma camera showed that the motility stimulated by SCFAs was propulsive and that the ileum was thereby emptied. We also tested whether SCFAs were equally effective stimuli during fasting and after food. SCFAs were equally effective during fasting and soon after food, but in the late postprandial period, when the meal reached the ileum, SCFAs were much less likely to stimulate motility. These observations shed further light on the capacity of the ileum to sense and react to the nature of the contents.     

Ileal short-chain fatty acids inhibit transpyloric flow in pigs

BACKGROUND: Short-chain fatty acids (SCFA) found in the ileum after caecoileal reflux might trigger a physiologic ileal brake similar that induced by ileal nutrient infusion. This study evaluates gastric emptying and motility after ileal administration of SCFA. METHODS: In eight conscious pigs gastric emptying was evaluated by double dilution (liquids) and direct measurement of duodenal effluent (liquids and solids) during ileal infusions of SCFA and isotonic and hypertonic saline. Antropyloroduodenal manometry and flow were recorded concurrently. RESULTS: Ileal SCFA significantly delayed gastric emptying of liquids and solids. During SCFA infusion the emptying pattern of liquids was less pulsatile, and flow pulses had a smaller stroke volume than during isotonic saline. The antroduodenal pressure gradient was decreased, whereas pyloric tone was increased. A reduced number of antral pressure waves occurred together with an increased frequency of isolated pyloric pressure waves. CONCLUSIONS: Ileal SCFA infusion delays gastric emptying of liquid and solid as a consequence of a decreased antral and increased pyloric motility.     

The effect of starch malabsorption on fecal short-chain fatty acid excretion in man

To study the impact of starch malabsorption on fecal short-chain fatty acid concentrations, 11 healthy volunteers consumed a controlled diet rich in starch for 2 4-week periods. They received the glucosidase inhibitor acarbose (Bay g 5421) in one of the study periods and placebo in the other. Stool wet weight increased by 68% and stool dry weight by 57% with acarbose. The fecal concentration (mumol/g wet weight) of n-butyrate (+58%) rose significantly when acarbose was added to the diet. The fecal excretion (mmol/day) of total short-chain fatty acids (+95%) and of their constituents acetate (+97%) and n-butyrate (+182%) was significantly higher when starch malabsorption was induced by acarbose.     

Influence of n-3 polyunsaturated fatty acids on soluble cellular adhesion molecules as biomarkers of cardiovascular risk in young healthy subjects

Background and aimSerum levels of soluble cellular adhesion molecules (CAMs) and blood lipid parameters have been used as markers of inflammatory processes associated with cardiovascular disease (CVD) events. The present study evaluated the effects of the intake of n-3 polyunsaturated fatty acids (PUFAs) in fish and fish oil within energy-restricted diets, on soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1).Methods and resultsTwo hundred and seventy-five healthy European subjects aged between 20 and 40 years, were randomized to one of four hypocaloric dietary groups: control (sunflower oil capsules, no seafood), lean fish (3 × 150 g portions of cod/week), fatty fish (3 × 150 g portions of salmon/week), fish oil ((docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) capsules, no seafood)). Diets rich in lean fish significantly decreased ICAM-1 levels, around 5% from baseline to endpoint (p < 0.05), and had no effect on VCAM-1 levels. No significant differences were observed in sICAM-1 levels after the intervention with fatty fish or fish oils. On the other hand, these two seafood based diets were responsible for a significant increase of VCAM-1 levels [fatty fish; 16.1% and fish oil; 21.9%] respectively (p < 0.05).ConclusionsCAMs as inflammatory biomarkers in young and healthy subjects are not conclusive for the evaluation of CVD risk. Hypocaloric fish diets had a different effect on CAMs, being lean fish responsible for the highest decrease in ICAM-1. On the other hand, VCAM-1 results allow speculation that a low dose of n-3 PUFA may be anti-inflammatory contrarily to a high dose which can have a pro-inflammatory effect. CAMs mechanism is complex and affected by multiple factors such as lifestyle, gender, and n-3 dose and source.     

Serum levels of short-chain fatty acids in cirrhosis and hepatic coma

Short-chain fatty acids cause reversible coma in animals and may contribute to the pathogenesis of the hepatic coma in humans. The concentrations of short-chain fatty acids in peripheral venous blood were significantly elevated in 15 patients with hepatic encephalopathy caused by cirrhosis (362 +/- 83 mumol/L; mean +/- S.E.M.) compared with 17 cirrhotic patients without encephalopathy (178 +/- 57 mumol/L) and 11 normal individuals (60 +/- 8 mumol/L). However, no correlation between the depth of coma and the level of short-chain fatty acids was found after repetitive measurements in the coma group. Compared with normal individuals, all short-chain fatty acids, except valerate, were elevated in patients with hepatic encephalopathy, whereas only the concentrations of isobutyrate and isovalerate were significantly elevated in cirrhotic patients without encephalopathy. The concentrations of short-chain fatty acids in 21 nonencephalopathic cirrhotic patients who underwent catheterization were equally distributed in the aorta (187 +/- 56 mumol/L), the hepatic vein (212 +/- 75 mumol/L), the azygos vein (140 +/- 37 mumol/L) and the renal vein (135 +/- 43 mumol/L) compared with peripheral venous blood (178 +/- 57 mumol/L). This study does not support the idea that short-chain fatty acids are of major importance in the pathogenesis of hepatic coma in patients with cirrhosis.     

Absorption of short-chain fatty acids from the human ileum

Acetate, propionate, andn-butyrate are the major short-chain fatty acid (SCFA) anions in the gastrointestinal tract of animal and man, accounting for 90% of total SCFA in stool water. Their absorption from the human ileum was investigated in 8 volunteer subjects by the triple-lumen perfusion technique. Each test solution contained one of the SCFAs at a concentration of 0–100 mM; sodium, potassium, and bicarbonate concentrations were kept constant, as were pH and osmolality. Absorption of each SCFA was found to be rate-limited with an apparentK _m between 22 and 27 mM and a calculatedV _max between 0.54 and 0.82 mmol/hr cm. Water, sodium, and chloride transport were not affected by substantial rates of SCFA absorption. Rather, significant stimulation of calculated bicarbonate secretion and a rise in intraluminal pH were consistently observed. The results are compatible with either of two mechanisms for SCFA absorption: an anion exchange between bicarbonate (or hydroxyl) and SCFA ions, or protonation of the SCFA anion at the mucosal surface followed by simple diffusion of nonionized SCFA into the absorbing cell.This work was supported, in part, by a grant (RR-58) from the General Clinical Research Center Program of the Division of Research Resources and by a research grant (AM-12985-05) from the National Institutes of Arthritis, Metabolic and Digestive Diseases, National Institutes of Health, Bethesda, Maryland.Presented, in part, at the Annual Meeting, Central Society for Clinical Research, November 6, 1976, Chicago, Illinois.Dr. Schmitt was supported by a Special Post Doctoral Research Fellowship Award (5-F03-AM53883) from the National Institute of Arthritis, Metabolic and Digestive Diseases, National Institutes of Health, Bethesda, Maryland.