Short-chain Fatty Acids Spectrum Research Articles

Metabolic Profiles of the Gut Microbiota in Patients with Different Stages of Metabolism Dysfunction-Associated Fatty Liver Disease

Aim: to study the metabolic activity of the intestinal microbiota depending on the stage of metabolic dysfunction-associated fatty liver disease (MAFLD). Materials and methods. The study included 85 patients with MAFLD (27 patients with steatosis without steatohepatitis and fibrosis, 42 patients with steatohepatitis, 16 patients with cirrhosis as an outcome of MAFLD, Child — Pugh class A–B) and 20 healthy people who formed the control group. The level and spectrum of short-chain fatty acids (SCFA) were determined by gas-liquid chromatography. Results. It was found that patients with MAFLD at the stage of steatosis and cirrhosis of the liver have unidirectional changes in the metabolic activity of the intestinal microbiota. We established a decrease in the absolute concentrations of SCFA — their total content, the level of acetate, propionate, butyrate, a decrease in the level of isoacids. The SCFA profiles showed an increase in the proportion of acetate and a decrease in propionate and butyrate. Moreover, changes in the named parameters of SCFAs are aggravated with progression to liver cirrhosis. At the stage of steatohepatitis, we identified two subgroups of patients with different levels of metabolic activity of the microbiota. Patients whose microbiota metabolism for SCFA production was high had correspondingly elevated SCFA levels. And, on the contrary, patients in whom the metabolic activity of the microbiota was reduced were characterized by a steady decrease in SCFAs and disease progression to liver cirrhosis. In the study, we showed an inverse correlation between the calculated prognostic indices of NFS and FIB-4, elastography values with the total level of SCFA, the level of acetate, propionate, butyrate. Thus, a decrease in the content of SCFA for patients with MAFLD can be considered as a prognostic marker of an unfavorable course of liver disease.

Short-chain fatty acids are potential goalkeepers of atherosclerosis.

Short-chain fatty acids (SCFAs) are metabolites produced by gut bacteria and play a crucial role in various inflammatory diseases. Increasing evidence suggests that SCFAs can improve the occurrence and progression of atherosclerosis. However, the molecular mechanisms through which SCFAs regulate the development of atherosclerosis have not been fully elucidated. This review provides an overview of the research progress on SCFAs regarding their impact on the risk factors and pathogenesis associated with atherosclerosis, with a specific focus on their interactions with the endothelium and immune cells. These interactions encompass the inflammation and oxidative stress of endothelial cells, the migration of monocytes/macrophages, the lipid metabolism of macrophages, the proliferation and migration of smooth muscle cells, and the proliferation and differentiation of Treg cells. Nevertheless, the current body of research is insufficient to comprehensively understand the full spectrum of SCFAs' mechanisms of action. Therefore, further in-depth investigations are imperative to establish a solid theoretical foundation for the development of clinical therapeutics in this context.

Low Short-Chain-Fatty-Acid-Producing Activity of the Gut Microbiota Is Associated with Hypercholesterolemia and Liver Fibrosis in Patients with Metabolic-Associated (Non-Alcoholic) Fatty Liver Disease

The aim of this study was to investigate the short-chain fatty acid (SCFA) activity of the gut microbiota of patients with metabolic-associated fatty liver disease (MAFLD). The level and spectrum of short-chain fatty acids (SCFAs) were determined via gas–liquid chromatography. Liver fibrosis was assessed using the FIB-4 index and elastography. Among 42 non-cirrhotic MAFLD patients, 24 had high fecal SCFA levels (group H) and 18 had low fecal SCFA levels (group L). Patients in group H had lower serum uric acid, total cholesterol, and LDL cholesterol levels but a higher BMI than those in group L. All patients in group L and only 37.9% of those in group H were found to have hypercholesterolemia. In patients with hypercholesterolemia, the level of SCFAs was lower than that in patients without hypercholesterolemia. Patients in group H had less liver fibrosis than patients in group L. A total of 50.0% of the patients in group H and 92.3% of those in group L had significant liver fibrosis (≥F2). Patients with significant liver fibrosis had lower levels of fecal SCFAs—particularly acetate and butyrate. The fecal SCFA levels were positively correlated with gamma-glutamyl transferase, total bilirubin levels, BMI, and platelet count and were negatively correlated with FIB-4, liver stiffness, serum total, and LDL cholesterol levels.

Differences in Fecal Short-Chain Fatty Acids between Alcoholic Fatty Liver-Induced Cirrhosis and Non-alcoholic (Metabolic-Associated) Fatty Liver-Induced Cirrhosis.

The objective of this study was to investigate the metabolic activity of the gut microbiota in cirrhosis due to different variants of fatty liver disease (alcoholic vs. non-alcoholic [metabolic-associated] one [AFLD and MAFLD]). The present study included 24 patients with alcoholic liver cirrhosis, 16 patients with MAFLD-related cirrhosis, and 20 healthy controls. The level and spectrum of short-chain fatty acids (SCFAs) were determined via gas-liquid chromatography. All patients with cirrhosis showed a decrease in the total content of SCFAs (p < 0.001) and absolute content of acetate (p < 0.001), propionate (p < 0.001), butyrate (p < 0.001), and isovalerate (p < 0.001). In MAFLD cirrhosis, the metabolic activity of the microbiota was significantly altered compared to patients with alcoholic cirrhosis, as evidenced by a lower total SCFA content (p < 0.001) and absolute content of acetate (p < 0.001), propionate (p < 0.001), and butyrate (p < 0.001); a higher relative content of isovalerate (p < 0.001); and a higher IsoCn/Cn ratio (p < 0.001). Various clinical and laboratory parameters correlate differently with fecal SCFAs and their fractions in cirrhosis due to AFLD and MAFLD. SCFA-producing metabolic activity is reduced more in MAFLD cirrhosis than in alcoholic cirrhosis. According to the etiological factors of cirrhosis, disorders of this metabolic activity may be involved in different pathogenetic pathways.

Спектр короткоцепочечных жирных кислот при хроническом панкреатите

The aim was to evaluate the metabolic activity of the colonic microbiota in patients with chronic pancreatitis (CP) as a marker of changes in the functional state of the pancreas. Material and methods. 40 patients (20 men and 20 women) aged 35 to 74 years (50.6 ± 9.4 years) were examined, 26 patients of which had external secretory pancreatic insufficiency (ESPI), which was confirmed by the data of the elastase test, and 14 patients had no ESPI. The diagnosis of CP was established on the basis of instrumental data. Patients with proven ESPI received enzyme replacement therapy (ERT) in accordance with international and Russian recommendations. The concentration and spectrum of short-chain fatty acids were evaluated by gas-liquid chromatography. The control group consisted of 22 healthy volunteers (13 women and nine men aged 43.4± 6.2 years). Results. As a result of the analysis of the profiles of short-chain fatty acids (SCFAs), a significant change in the content of propionic acid was revealed in patients with CP without GNP when compared with a group of healthy volunteers, no differences were found between the groups of patients with CP. These studies indicate a decrease in the activity of certain types of colon microbiota that produce C3 (propionic acid) in patients with CP without ESPI and, accordingly, who did not receive ERT. This, apparently, is due to the violation of the fermentation of individual substrates entering the lumen of the colon. Conclusion. Indicators of the concentration and spectrum of SCFAs can serve as additional tools for detecting changes in the metabolic activity of the colonic microbiota as a marker of the functional state of the pancreas in CP.

Влияние аглютеновой диеты на метаболическую активность кишечной микробиоты у больных целиакией

The aim is to study the effect of the gluten-free diet (GFD) on the spectrum of short-chain fatty acids (SСFAs) in the intestine in patients with celiac disease. Material and methods. 61 patients with celiac disease were examined, confirmed by positive serological tests and histological examination of the mucous membrane of the small intestine. Men were 17 (13.7%), median age – 41 years; women – 44 (86.3%), median age – 45 years. The first group included patients with newly diagnosed celiac disease (n = 21); the second group included patients who observe GFD, consciously or unconsciously violate it (n = 20); the third group consisted of patients who strictly observe GFD (n = 20). The duration of dietary treatment of patients of the second group ranged from two hundred months to seven years, in patients of the third group – from one year to eight years.The level of SСFAs in feces was determined by gas-liquid chromatography on the Crystal 2000 M chromatograph. The control group consisted of 22 healthy volunteers, among them were 6 (27.3%) men, 16 (72.7%) women, the median age was 42 years (Q1-Q3: 32–58 years; Shapiro p-value &lt; 0.01). Statistical analysis was performed using parametric and nonparametric methods according to the Statistica 13.3 program (StatSoft Inc., USA). Results. The total level of SCFAs in the coprofiltrate of patients of the first group was slightly higher than in the control group (13.15 ± 1.52 vs 9.8 ± 2.1 mg/g; p = 0.278), the anaerobic index was significantly higher (1.43 ± 0.23 vs 0.754 ± 0.15 mg/g; p = 0.017), which indicated an increase in the metabolic activity of anaerobic bacteria. Significant differences in patients of the first group and in the control group were obtained in the levels of propionic acid (3.85 ± 0.62 vs 1.65 ± 0.46 mg/g; p = 0.006); isobutyric acid (0.67 ± 0.1 vs 0.28 ± 0.1 mg/g; p = 0.009) and valerian acid (0.83 ± 0.13 vs 0.32 ± 0.09 mg/g; p = 0.002). In patients of the second group, a significant decrease in the total amount of SCFAs was found compared with the control group (4.6 ± 0.9 vs 9.8 ± 2.1 mg/g; p = 0.034). Also, in the second group, compared with the control group, a significant decrease in the concentration of acetic acid was revealed (1.9 ± 1.2 vs 5.36 ± 1.1 mg/g; p = 0.045). The level of isovaleric acid was increased in the second group compared to the third group (0.66 ± 0.14 vs 0.22 ± 0.13 mg/g; p = 0.04), and the level of capronic acid concentration was reduced (0.05 ± 0.1 vs 0.35 ± 0.1 mg/g; p = 0.04). These data indirectly indicated a decrease in the number of representatives of the saccharolytic microflora in the second group. Conclusion. When studying the spectrum and concentration of SCFAs in the feces of patients with celiac disease who are at different stages of treatment of GFD and recovery of MMSI, there is a tendency to multidirectional metabolic activity of the colonic microbiota. As the GFD is observed, the overall level of SCFAs decreases, there is a shift in the ratio of anaerobes and aerobic bacteria, the level of isovaleric acid increases and the tendency to increase isobutyric acid decreases, the level of acetic and caproic acids decreases. To optimize the treatment of patients with celiac disease, further monitoring of the metabolic activity of the intestinal microbiota in the process of dynamic observation is required.

Evaluation of the intestinal microbiota and short-chain fatty acids content in patients with chronic inflammatory bowel diseases

Background. The pathogenesis of chronic inflammatory bowel disease (IBD) is still not fully clarified. It is known that disorders of the intestinal microbiota lead to an increased intestinal permeability, activation of mucous and adaptive immunity, impaired production and intestinal absorption of short-chain fatty acids (SCFA). The ratio of acetic, propionic, butyric acids is an important indicator of the integrity of the intestinal microbial community. Thus, the study of the composition of the intestinal microbiota and the concentrations of fecal SCFA is a very promising approach to broadening the understanding of IBD pathogenesis. The purpose of our study was to determine the features of the production of fecal SCFA and the composition of colon microbiota in patients with IBD. Materials and methods. The study, which was carried out at the Department of Intestinal Diseases of the Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine, involved 74 patients with IBD with an average age of (43.2±1.8) years, who according to nosology were divided into 2 groups: group I— those with ulcerative colitis (UC) (n=66), group II— individuals with Crohn’s disease (CD) (n=8). The diagnoses of CD and UC were established according to generally accepted diagnostic standards in gastroenterology. Determination of fecal SCFA was carried out by chromatographic method with the use of hardware-software complex for medical researches on the basis of the gas chromatographer Chromateс Crystal 5000. The intestinal microflora was evaluated using a microbiological study of the colon content. Results. Patients with IBD had significant changes in the spectrum of SCFA, which were similar in both UC and CD: a decrease in acetic acid in the UC group by 5.7 times, in the CD group by 10.5 times (p&lt;0.05), butyric acid in the UC group by 1.6 times, in the CD group by 1.5 times (p&lt;0.05), and an increase in propionic acid in the UC group by 4 times and in the CD group by 3.3 times (p&lt;0.05) compared with the control group. There was also a significant increase in the anaerobic index in patients with IBD. Microbiological study of feces showed a significant decrease in Lactobacillus, which was observed in all patients with IBD, as well as a decrease in Bifidobacterium in 19.7% of those with UC and in 37.5% with CD. There was a decrease of other representatives of the normal microflora: Enterococci (in 15.2% in the UC group and 25% in the CD group) and Escherichia coli (in 15.2% in the UC group and 12.5% in the CD group). Excessive growth of opportunistic flora was also detected: hemolytic Escherichia coli was increased in 19.7% of patients with UC and in 12.5% of those with CD; Proteus was detected in 12.1% of people with UC and in 37.5% with CD. The excessive growth of Candida was found in 43.9% of patients in the UC group and in 87.5% of individuals with CD. Conclusions. Quantitative and qualitative deviations of the intestinal microbiota, such as a decrease in the number of major symbionts and an increase in the number of opportunistic pathogens, were observed in all examined patients with IBD. The obtained results showed that changes in SCFA concentrations in both nosologies of IBD differed significantly from those in the control group, which in combination with primary genetic defects of the barrier function of the epithelium and its regenerative ability can lead to deterioration in the course and prognosis of IBD. Evaluation of the ratio of SCFA fractions with the calculation of the anaerobic index may be useful for the diagnosis of intestinal dysbiosis in patients with IBD.

Оценка состояния интестинальной микрофлоры и содержания короткоцепочечных жирных кислот копрофильтрата у детей с неалкогольной жировой болезнью печени

Актуальность. Качественные и количественные изменения кишечного микробиома способствуют развитию и прогрессированию неалкогольной жировой болезни печени (НАЖБП). Девиации представительства кишечной микрофлоры ассоциированы с повышением кишечной проницаемости, активацией врожденных и адаптивных иммунных реакций, увеличением продукции и всасывания в кишечнике короткоцепочечных жирных кислот (КЖК). Соотношение уксусной, пропионовой и масляной кислот является важным показателем целостности микробного сообщества кишечника. Таким образом, изучение состава кишечной микробиоты и продукции короткоцепочечных жирных кислот представляет собой перспективное направление, способствующее пониманию механизмов, приводящих к развитию НАЖБП у детей. Цель работы: изучить особенности состояния кишечной микрофлоры и содержания фекальных короткоцепочечных жирных кислот у детей с НАЖБП. Материалы и методы. Комплексное обследование 102 детей было проведено в отделении детской гастроэнтерологии Института гастроэнтерологии Национальной академии медицинских наук Украины. В зависимости от наличия ожирения, данных транзиентной эластографии и уровня аланинаминотрансферазы пациенты были разделены на четыре группы: I группа — дети с простым стеатозом печени (n = 24); II группа — дети с неалкогольным стеатогепатитом (НАСГ) (n = 14); III группа — дети с ожирением без стеатоза (n = 48), IV группа — дети с нормальным весом (n = 16). Хроматографическое исследование КЖК проводилось с помощью газового хроматографа «Хроматек-Кристалл 5000». Идентификация микроорганизмов осуществлялась с использованием микробиологического исследования содержимого толстой кишки. Диагноз НАЖБП подтвержден при помощи аппарата «FibroScan 502 Touch» (Echosens, Франция) с определением контролируемого параметра затухания ультразвука. Результаты. У детей с ожирением (III группа) выявлены значительные изменения в спектре КЖК: увеличение содержания уксусной кислоты в 4,8 раза (р &lt; 0,05), пропионовой кислоты в 1,5 раза (р &lt; 0,001) и масляной кислоты в 1,7 раза в сравнении с контрольной группой. У детей с НАСГ содержание уксусной кислоты в копрофильтрате было увеличено в 2,5 раза, пропионовой и масляной кислот в 1,4 раза по сравнению с контрольной группой (р = 0,1). Также наблюдалось значительное снижение анаэробного индекса у пациентов с НАЖБП. Микробиологическое исследование кала продемонстрировало снижение количества бифидобактерий у 11,8 % пациентов I группы и у 8,3 % III группы; снижение содержания Lactobacillus у 70,6 % детей I группы, у всех детей с НАСГ, у 70,8 % пациентов III группы. Избыточный рост Klebsiella обнаружен у 23,5 % пациентов I группы и у 8,3 % детей III группы. Патогенный стафилококк выявлен у 5,9 % пациентов I группы, у 8,3 % пациентов III группы. Избыточный рост Candida был выявлен у 23,5 % детей I группы, у 14,3 % детей II группы и у 20,8 % детей III группы. Выводы. У детей с НАЖБП и ожирением наблюдаются количественные и качественные изменения кишечной микробиоты в виде уменьшения численности основных симбионтов и увеличения представительства условно-патогенной микро­флоры. Наиболее выраженные изменения спектра фекальных КЖК были обнаружены у детей, страдающих ожирением, что может свидетельствовать о значимости нарушений микро­флоры кишечника на ранних стадиях развития НАЖБП. Определение соотношения фракций фекальных КЖК с вычислением анаэробного индекса может быть полезным для оценки состояния кишечной микрофлоры у детей с НАЖБП.

Dysbiosis of Gut Microbiota and Short-Chain Fatty Acids in Acute Ischemic Stroke and the Subsequent Risk for Poor Functional Outcomes.

BackgroundThe intestinal microbiota and its metabolites have been reported to play an important role in stroke. Gut microbiota–originating short‐chain fatty acids (SCFAs) modulate brain functions directly or indirectly through immune, endocrine, vagal, and other humoral pathways. However, relatively few investigations have evaluated the gut microbiome and SCFAs spectrum or their potential associations with stroke outcomes in acute ischemic stroke (AIS) patients with different stroke severities.MethodsWe used 16S rRNA gene sequencing and gas chromatography to compare the fecal microbial composition and SCFA spectrum between AIS patients (n = 140) and healthy controls (n = 92). Their associations with 90‐day poor functional outcomes were evaluated by logistic regression models.ResultsWe found that the intestinal microbiota distinguished AIS patients from healthy controls. A lack of SCFAs‐producing bacteria and a low fecal SCFAs level defined dysbiosis in AIS patients, especially those with increased stroke severity. The SCFAs levels were negatively correlated with stroke severity and prognosis. Reduced SCFAs levels, especially acetate, were associated with an increased risk of 90‐day poor functional outcomes even after adjustments.ConclusionsDysbiosis of SCFAs‐producing bacteria and SCFAs in AIS patients increased the subsequent risk for poor functional outcomes, indicating that SCFAs could be potential prognostic markers and therapeutic targets for stroke.

Recovery of the Intestinal Microbiota Metabolic Activity in Patients with Bronchial Asthma

Aim . To investigate the feasibility of correcting the content and profile of short-chain fatty acids (SCFA) in feces of patients suffering from allergic bronchial asthma. Materials and methods . The study included 30 patients with allergic bronchial asthma (BA). All patients underwent a generally accepted range of clinical laboratory tests, functional respiratory tests and a hydrogen breath test with lactulose to detect SIBO. The SCFA spectrum was determined by gas-liquid chromatographic analysis. All patients with BA underwent standard basic therapy with combined preparations containing long-acting beta-2-adre nergic agonists and inhaled glucocorticoids. For the treatment of SIBO, 10 patients were prescribed rifaximin-α at a dose of 200 mg × 3 times a day for 7 days, 10 patients were prescribed rifaximin-α at the same dose, followed by the administration of the Lactobalans drug containing at least 3.0×10 9 CFU/caps. probiotic microorganisms ( Lactobacillus gassery KS-13, Lactobacillus gasser LAC-343, Lactobacillus ramnosus LCS-742, Bifi dobacterium bifi dum G9-1, Bifi dobacterium longum MM-2, Bifi dobacterium longum BB536 Strain M, Bifi dobacterium biumidum BB536 Strain M. Bifi dobacterium biumidum biumidum BB536 Strain M. lactis B1-04) in 1 capsule once a day for 1 month. A probiotic course of 1 month was assigned to 10 patients without SIBO as part of the complex treatment of BA. The study of SCFA was carried out in all groups immediately after the end of probiotic therapy (after 1 month). Results. All patients demonstrated normalisation of the SCFA spectrum and anaerobic index. In patients without SIBO, during a probiotic therapy, an increase in the total content of SCFA ( p &lt;0.001), acetic and butyric acid ( p &lt;0.001) was revealed. The administration of a probiotic after a course of rifaximin-α led to a decrease in the relative amount of isoacids and the isoacids/acids ratio in comparison with patients who received rifaximin-α only for treatment of SIBO ( p &lt;0.05). Conclusion. The obtained results demonstrate the potential of drugs in affecting the composition and number of active bacterial metabolites of the intestinal biotope, which indicates the restoration of intestinal microbiocenosis.

Intestinal Short-Chain Fatty Acids in Patients with Bronchial Asthma

Aim. Tostudy the content and profile of short-chain fatty acids (SCFAs) in faeces of patients with bronchial asthma and healthy individuals, as well as to evaluate possible correlations between the SCFA spectrum and clinical phenotype of patients with bronchial asthma. Materials and methods. 44 patients with asthma and 17 healthy volunteers participated in the study. All participants underwent a generally accepted range of clinical and laboratory studies, as well as functional respiratory tests. The SCFA spectrum was determined using gas-liquid chromatographic analysis. The results of patients with asthma showed a significant decrease in the total fatty acid content in faeces (p &lt;0.001); changes in the absolute concentrations of individual acids, such as acetate (p &lt;0.001), propionate (p &lt;0.001) and butyrate (p &lt;0.001); as well as a change in the total isoacid content (p &lt;0.001). In 83% of the cases, the anaerobic type of the SCFA spectrum was detected. The aerobic type of the SCFA metabolic profile was detected in 17% of the cases. The change in the metabolic profile did not depend on the phenotype of the disease.Conclusion. Changes in SCFAs indicate pronounced disorders in the microbiocenosis of the intestinal biotope. The values of the anaerobic index in the context of various changes in the acid metabolic profile indicate the disturbance of the microorganism’s habitat, contributing to the growth of anaerobic or aerobic microflora populations.

Metabolic activity of intestinal microflora in patients with bronchial asthma.

The gut microbiota plays the important role to support the immunological tolerance. To study a metabolic activity of the intestinal microflora the 44 patients suffering from bronchial asthma and 17 healthy volunteers were tested. The short-chain fatty acids (SCFA) spectrum was determined using the method of gas-liquid chromatographic analysis. We have detected a significant decrease the total content of the fatty acids in the feces (P<0.001), the absolute concentrations of the individual acids (acetate, propionate, butyrate; P<0.001) and the total content of isoacids (P<0.001) for all of the patients with bronchial asthma in the study, regardless of the phenotype. The anaerobic type of the SCFA spectrum was detected for the majority (83%) of the patients tested. The aerobic type of the SCFA metabolic profile was detected for another part (17%) of the patients tested. Being detected the parameters change could play the principal role as for the bronchial asthma course as to support the organism sensibilisation.

The Influence of Propionate on the Spectrum of Short-Chain Fatty Acids in Cervical Cells During Dis- and Neoplastic Transformation

Introduction. There is some data of the short-chain fatty acids (SCFA) participation in cancerogenesis. The cervical cancer is an “ideal” model for determining the molecular mechanisms underlying the development of cancer. The aim of study was to estimate the influence of propionate on the spectrum of SCFA in cervical cells during dis- and neoplastic transformation. Materials and methods of research. Materials of the study - cervical biopsy verified morphologically. Study groups: IA - the focus of the pretumor lesion of cervix; IB - paradisplastic cells; IIA - locus of cervical cancer; IIB - paraneoplastic cells. The spectrum of fatty acids was analyzed before, after 24 hours incubation with 50 μmol/l propionic acid by the gas chromatography method. Methods of nonparametric statistics the Mann-Whitney test were used. Differences were considered statistically significant at p<0.05. Results of the study. The incubation of cervical cancer cells with propionate leads to an increase the level of propionate and butyrate. The incubation of precancer, paraneoplastic and paradisplastic cells leads to an increase the levels of isobutyric, valeric and caproic acids against the background of a significant drop in the concentration of propionate and butyrate. Сonclusion. It can be concluded that the effect of propionate on the metabolism of fatty acids in the cervical epithelium of the studied samples is multidirectional and depends on the cell type. The dates indicate the modifications of SCFA in the cervical carcinogenesis.

Age-related changes in production of shortchain fatty acids by gut microbiome in patients without gastroenterological diseases

Rationale: Multiple biological effects of short chain fatty acids (SCFA) and the possibility to modify their composition by probiotics and prebiotics is in the focus of attention of researchers and clinicians. However, big studies with assessment of the whole spectrum of SCFA produced by gut microbiome and calculated indexes of their relative content are lacking. Aim: To determine concentrations and ratios of fecal SCFA (functional activity of the gut microbiome) depending on the age of patients without gastrointestinal disorders. Materials and methods : SCFA fecal concentrations were measured by gas liquid chromatography in 6836 patients aged from 1 month to 85 years without any functional or chronic gastrointestinal pathology, infectious diseases and/or obesity. The time periods with homogenous values of the parameters were determined by identification of constant trends of their means (medians) with 1-month accuracy in children below 5 years of age and with 1-year accuracy in the patients above 1 years of age. The results obtained for the chosen time intervals were compared with Mann-Whitney's test at 95% significance level (p < 0.05). Results: We performed descriptive statistics for absolute and relative content of SCFA and their structural indexes. It was shown that the parameters characterizing functional activity of gut microbiome have different critical stages in their age-related changes. For each parameter, 2 or 3 stages of changes were identified that occurred at early age, mainly before the age of two. The final SCFA structure was stable by 2 years and 5 months of age. Total SCFA levels reached those typical for adults by the age of 12. The structural index was most sensitive to integrated changes of the microbiome structure. Conclusion: Age-related characteristics of gut microbiome should be taken into account when performing clinical studies on effectiveness of therapeutic interventions and assessing the parameters in a given patient.

PATHOGENIC AND CORRELATIVE RELATIONSHIP BETWEEN THE LEVEL OF SHORT- CHAIN FATTY ACIDS AND THE INTENSITY OF BIOLOGICAL PROCESS IN CERVICAL CANCER CELLS DURING CANCEROGENESIS

Background. The change in the spectrum of short-chain fatty acids (SCFA) is known to be one of the links of carcinogenesis. The aim of study was to assess the correlation between the levels of cell proliferation, apoptosis, cell cycle kinetics and the spectrum of short-chain fatty acids in cervical dysplasia and cancer cells. Methods. To analyze the association between the variables, the Spearman’s rank correlation was used. Results. The SCFA is likely to have anti-proliferative, pro-apoptotic, and modulatory effects on the cell cycle phase. Conclusion. Correlations between the level of SCFA and parameters of apoptosis, necrosis, and cell cycle phases indicates their pathogenetic participation in the cervical carcinogenesis.

THE METABOLIC ACTIVITY OF THE MICROFLORA OF THE OROPHARYNX IN CHILDREN WITH BRONCHITIS AND COMMUNITY-ACQUIRED PNEUMONIA

Background: Given a steady increase in the number of children with recurrent respiratory tract infections, to develop methods of their rehabilitation, it is necessary to evaluate factors of nonspecific resistance. Aim: To study metabolic activity of oropharyngeal microflora in children with recurrent bronchitis and community-acquired pneumonia, based on determination of spectrum of shortchain fatty acids (SCFA). Materials and methods: This prospective study included 60 children with recurrent respiratory tract infections aged from 3 to 7 years, hospitalized for inpatient treatment of bronchitis (n = 30) and pneumonia (n = 30). The oropharyngeal microflora was assessed by classical bacteriological method (in mucosal smears); SCFA levels in non-stimulated saliva were measured by gas liquid chromatography. Results: There was no significant difference in qualitative and quantitative composition of the oropharyngeal microflora between children with bronchitis and pneumonia. However, assessment of metabolic functions showed some significant differences. Children with bronchitis showed signs of microflora hyperactivation with total SCFA production up to 118.4% (mean) from that of the reference range, with predominant activation of aerobic bacteria (anaerobic index 66.8%). In children with pneumonia, microflora was suppressed (68.13% of the normal range, the difference with the bronchitis group being significant, p 0.05). Conclusion: The data obtained could be used to make a decision on the necessity of antibacterial therapy.

Importance of small intestinal bacterial overgrowth in chronic pancreatitis

Importance of small intestinal bacterial overgrowth in chronic pancreatitis

PREBIOTIC OLIGOSACCHARIDES IN INFANT NUTRITION: ADDITION OF ONLY GALACTOOLIGOSACCHARIDES DOES NOT INDUCE FAECAL ACIDIC PH AND SCFA-SPECTRUM TYPICAL FOR BREAST FED INFANTS

Introduction: Recently, the ESPGHAN Committee on Nutrition summarised available information on the effects of adding prebiotic oligosaccharides to infant formulae. The Committee commented that only the combination of galactooligosaccharides (GOS) and fructooligosaccharides (FOS) was tested in controlled infant feeding studies and that future trials should define optimal quantity and quality of oligosaccharides with prebiotic function. We present data on a study with an infant formula supplemented with only GOS. These data can be compared with those from a previous study where a formula with a mixture (90% GOS and 10% FOS) is investigated using an identical protocol, formula matrix and analytical methods. Methods: Before birth, infants from mothers intending to formula feed were at random and double blindly allocated to one of two formula groups. From birth until 16 weeks of age, the GOS formula group (n = 17) received formula supplemented with 0.6 g/100 ml GOS. The standard group (n = 17) received the infant formula without supplementation. Faecal samples were taken from the diapers at postnatal days 5, 10, and weeks 4, 8, 12 and 16. Percentage of bifidobacteria from total number of bacteria (analysed by fluorescence in situ hybridisation), total and relative amounts of short-chain fatty acids (SCFA), lactate concentration and pH were measured in faeces. Parallel to the two formula groups a breast-feeding group was followed using the same protocol. Results: Both formula groups revealed a highly similar development of faecal bifidobacterial flora. Faecal pH (6.5-7.0), SCFA total concentration (75-90 mmol/kg wet faeces) and -profile (acetate: 70-80%) were also very similar between both formula groups, but distinct from the breast feeding group (pH: 5.5-5.7; SCFA: 50-60 mmol/kg faeces; acetate: >85%). Under highly similar conditions nearly identical results were found earlier for a group fed standard formula (n = 19) and a parallel breast-fed group. However, the prebiotic group (n = 19) fed formula supplemented with 0.6 g/100ml GOS/FOS mixture clearly showed different faecal characteristics (pH 5.5-6.0; SCFA: 65-75 mmol/kg faeces; acetate: >80%), close to the ones for breast fed infants. Conclusions: In contrast to infant formula supplemented with a GOS/FOS mixture, infant formula supplemented with short chain GOS only, does not induce faecal acidic pH and SCFA-spectrum typical for breast-fed babies. This result supports the hypothesis that the long chain FOS components of the prebiotic mixture are fermented rather slowly, similar to polymeric human milk oligosaccharides, leading to a typical acidic pH and acetate-dominating SCFA spectrum in the distal part of the colon and the faeces.