Alterations In Intestinal Microflora Research Articles

Integrative concepts in asthma and allergy treatment in children: TCM

Traditional Chinese medicine (TCM) has considered the lung to be connected to the large intestine for 2000 years. According to the principles of TCM and the theory of the Five Elements any treatment aimed at the lung, as a Yin-organ, also implicates treatment and regulation of the large intestine, as the linked Yang-organ. This interaction between lung and large intestine was recently re-detected by epidemiological studies carried out to generate hypothesis of plausible mechanisms for the increasing prevalence of asthma and atopic diseases in developed countries. The “Hygiene Hypothesis” postulates that improvements in public health, hygiene practices and smaller family sizes result in a reduced exposure to TH 1-trophic microbial stimuli from both commensals and pathogens. Observations of altered intestinal microflora in allergic children and clinical studies elucidated the role of non-pathogenic microbes of the gut and the GALT as a major factor essential for the maturation of the immune system to a nonatopic mode. A randomised, placebo-controlled pilot study of laser acupuncture and probiotics in school age children with asthma showed a beneficial clinical effect on bronchial hyperreactivity. Acupuncture treatment of patients with allergic asthma resulted in a significant decrease in Th2 cytokines IL-4, IL-6 and IL-10 serum levels. Acupuncture in allergic rhinitis leads to clinically relevant and persistent benefits. Tentatively, it appears that acupuncture and Chinese herbal medicine can be effective in allergic rhinitis and asthma, but for confirmatory evidence larger, multi-centre trials are necessary. Recently, use of paracetamol and antibiotics for common cold diseases in the first year of life and the later childhood were shown to be associated with the risk of inducing asthma, rhino-conjunctivitis and eczema. A low risk for asthma-related morbidity was also shown for ibuprofen use in febrile children. How can TCM counteract these mechanisms? Shang han lun, the oldest surviving Chinese medical text devoted to externally contracted (common) cold diseases, presents a systematized knowledge concerning the origin and development of such diseases and their treatment by highly sophisticated use of herbs combined in formulae that are skillfully modulated to deal with a vast variety of disease manifestations. Examples will be presented. Strict guidelines on diet and lifestyle are essential in TCM and will be explained.

Small intestinal bacterial overgrowth

Abstract In the adult, the human intestine houses myriads of microorganisms, quantitatively up to 100 trillion and qualitatively over 500 species of bacteria, exceeding the number of host somatic cells by at least one order of magnitude. Actually, it remains a mystery as to how the intestine is able to contain such large quantities of bacteria without evident harm to the host. However, it is well known that a very complex symbiotic relationship between the intestinal microflora and the host insures mutual advantages for both partners. Despite the recent advances in immunology and microbiology, the possibility of studying human intestinal microflora is limited by great inter-individual variability and difficulties in creating standard conditions to uniform the samples. However, there are clinical conditions which are useful to explain the role of intestinal bacteria in the human gut. Small intestinal bacterial overgrowth (SIBO) is a good example, because this is a microbial alteration of intestinal microflora, in absence of pathogenic bacteria and severe dysregulation of the immune system. On the other hand, the pathogenesis and clinical aspects of SIBO could clarify the complex and bi-directional relationship between the microbiota and the host.

P1A recombinant beta-lactamase prevents emergence of antimicrobial resistance in gut microflora of healthy subjects during intravenous administration of ampicillin.

Ipsat P1A is a recombinant beta-lactamase which degrades antibiotic residue in the gastrointestinal tract. In an open-label, single-center controlled trial, 36 healthy subjects were randomized to receive (i) ampicillin (1 g intravenously [i.v.] every 6 h [q6h]), (ii) oral P1A recombinant beta-lactamase (8.2 mg q6h), or (iii) ampicillin (1 g i.v. q6h) in combination with oral P1A recombinant beta-lactamase (8.2 mg q6h) for 5 days. Fecal samples were collected before treatment, during treatment (days 3 to 5), and at follow-up (day 12). The primary end points were (i) changes in gastrointestinal microflora (determined by temperature gradient gel electrophoresis [TGGE]) and (ii) emergence of bacterial resistance (determined by conventional microbiology and PCR of TEM beta-lactamase genes). Thirty-five subjects completed the study. The mean similarity percentages of TGGE profiles between baseline and each treatment day sample were significantly lower for the ampicillin group than for the group receiving ampicillin plus P1A recombinant beta-lactamase on days 3, 4, and 5 (P < 0.001). Compared with the ampicillin group, subjects receiving ampicillin plus P1A recombinant beta-lactamase had significantly fewer ampicillin-resistant coliforms on days 3, 4, and 5 and at follow-up (P < or = 0.001) and fewer TEM beta-lactamase genes on days 3, 4, and 5 (P < 0.02). P1A recombinant beta-lactamase was safe and well tolerated. In healthy subjects, P1A recombinant beta-lactamase prevents ampicillin-induced alterations in intestinal microflora, emergence of resistance, and the number of TEM genes.

Changes of intestinal microflora in patients with rheumatoid arthritis during fasting and a Mediterranean diet

Background Therapeutic dietary interventions were often shown as effective treatment for rheumatoid arthritis (RA). Evidence 1a could be established for medical Fasting. The mechanisms to affect inflammation and clinical outcome are unknown. Alterations in intestinal microflora, especially the profile of short-chain-fatty-acids (SCFA) are believed to be associated with disease activity in patients with RA. Aim To evaluate changes in intestinal microflora and clinical outcome in RA during Fasting or a Mediterranean diet. We expect a greater influence of Fasting versus Mediterranean diet and a correlation between fasting response and alterations in SCFA. Methods In total, 50 consecutive patients from an Integrative Medicine Hospital were included in a prospective observational study. Patients received a 7-day Fasting therapy or a Mediterranean diet. Stool samples for gas-chromatographical analysis were taken at the beginning and at the end of a 2-week hospital stay. Disease activity of RA was assessed with DAS-28 and CRP was measured. Patients health assessment, self facility, pain and food consumption were evaluated with HAQ, SF-36, VAS and FFQ. Results DAS-28 decreased from 5.7±0.9 to 4.1±1.3 mean value in the fasting group and from 5.4±1.4 to 4.5±1.3 in non-fasters ( p =0.115). Pain on VAS significantly decreased from 4.1±2.3 at day 1 to 2.6±2.2 at day 7 in the fasting group versus 3.5±2.7 to 3.5±2.7 in the Mediterranean diet group ( p =0.049). CRP showed no significant difference ( p =0.759). No statistical differences between both groups were found in the profile of total-fatty-acids ( p =0.069), butyrate ( p =0.611) and propionate ( p =0.419), but measurement of acetate shows significant decrease from 17.4 μmol/g±9.8 to 21.4 μmol/g±16.4 in the fasting group compared to increasing values from 15.2 μmol/g±10.4 to 13.8 μmol/g±9.3 in the Mediterranean diet group ( p =0.044) (mean values). Conclusion Improvement of disease activity was comparable in both study groups. Pain decreased significantly on day 7 after Fasting therapy compared to Mediterranean diet and suggests a potential benefit of Fasting. Alterations in SCFA showed no significant differences except for the measurement of acetate. An association between anti-inflammatory properties of SCFA and disease activity in RA could not be shown.

Time-dependent persistence of enhanced immune response by a potential probiotic strain Lactobacillus paracasei subsp. paracasei NTU 101

The possible time-dependent role of lactic acid bacteria (LAB) in immunomodulation was investigated in BALB/c mice fed daily with Lactobacillus paracasei subsp. paracasei NTU 101 (10 8 colony forming units) for 3, 6, and 9 weeks, and following feeding with Lactobacillus-free food for a further 7 days. We observed up-regulation of the antigen-presenting ability of dendritic cells, and expression of natural killer group-2 D (NKG2D) molecules capable of trigger natural killer cell-mediated cytotoxicity. Lymphocyte proliferation and antibody production were also significantly increased in mice after treatment. Innate and adaptive immunity remained constant even at the most protracted feeding time, indicative of the time dependence of the bacterial-mediated enhanced immunity. To better correlate intestinal microflora with immunity, the intestinal contents of probiotics and harmful microorganisms were determined. Results showed an altered intestinal microflora, with increases in bifidobacteria and lactobacilli and a decreased content of Clostridium perfringens after feeding with L. paracasei subsp. paracasei NTU 101. It is possible that persistent activation of immunity might be induced by intestinal probiotics.

NOD2/CARD15 Gene Variants Are Linked to Failure of Antibiotic Treatment in Perianal Fistulating Crohn's Disease

The Crohn's disease (CD) susceptibility gene, nucleotide-binding oligomerizetion domain 2 (NOD2)/caspase recruitment domain 15 (CARD15), is linked to the innate immune response associated with altered epithelial bacterial defense. Its relevance in antibiotic therapy of perianal fistulating CD remains elusive. The aim of the study was to explore systematically the association between NOD2/CARD15 variants and clinical response of perianal fistulas in patients using antibiotic therapy. Fifty-two patients (median age 36 yr) with draining perianal fistulas were treated with ciprofloxacin (N = 49) or metronidazole (N = 3) for a median duration of 7 wk. Complete response was defined as the absence of any draining fistula despite gentle finger compression. Genotyping for NOD2/CARD15 variants and human beta (beta)-defensin 2 (HBD-2) copies was performed by 5' nuclease assays (Applied Biosystems, Foster City, CA). The examiners and laboratory investigators were blinded. The Fisher exact test and Wilcoxon signed rank test were used for statistical analysis. Ciprofloxacin was discontinued in one patient due to diarrhea after 2 wk. Complete fistula response was observed in 13 of 39 patients with NOD2/CARD15 wild-type (33.3%) compared with none in patients carrying NOD2/CARD15 variants (0%, P= 0.02). The median number of HBD-2 gene copies between responders and partial/nonresponders was similar. The study result suggests a substantial contribution of NOD2/CARD15 to the antibiotic treatment outcome of perianal fistulating CD. NOD2/CARD15 variants may predispose to an altered intestinal microflora in perianal fistulas that is less responsive to antibiotic treatment.

A natural approach to treatment of inflammatory bowel disease

Inflammatory bowel disease (IBD) comprises a spectrum of chronic inflammatory disorders whose precise aetiology remains elusive, although genetic, immunological and psychic factors are known to play a pathogenic role. Standard medical therapy includes corticosteroid in the acute phase, mesalazine or immunomodulants to maintain remission and biological agents for refractory and/or severe cases. Since the precise causation of IBD remains unclear, treatment is currently aimed at treating symptoms or, at best, general rather than specific pathophysiological changes, which accounts for the sometimes mediocre and unsatisfactory results often observed in clinical practice. Moreover, most of the drugs currently employed to treat IBD exert untoward effects, especially during long-term treatment. Recently a body of evidence has suggested a distinct role of enteric microbial flora in inducing and maintaining intestinal inflammation through a complex interplay with the gut immune system. Accordingly, certain antibiotics such as metronidazole and ciprofloxacin have been successfully employed, especially in Crohn's disease [1]. In view of the side-effects of prolonged administration of systemic antibiotics, rifaximin, a poorly absorbed, locally acting antibacterial agent, has also been tested, with promising results [1]. A safer and even more attractive therapeutic alternative is offered by probiotics, with or without the addition of prebiotics, a ‘natural’ approach to IBD treatment. In this issue of the Journal, Damaskos and Kolios [2] provide an exhaustive and interesting overview of the role of alterations in intestinal microflora (so-called dysbiosis) in IBD and the possible therapeutic effect of probiotics in restoring the balance, thus reducing or preventing intestinal inflammation. What is clear from the available clinical data and needs to be emphasized is the concept that probiotics, far from being all alike, exhibit profound differences in their mechanisms of action and therefore in their therapeutic effects, even within the same genre. Another important observation is that the observations carried out in experimental models do not necessarily predict what will actually take place in clinical practice. For example, Lactobacillus strains were found to attenuate colitis induced by various agents, but in the clinical setting proved to be ineffective in preventing relapse of Crohn's disease in both adults and children [3–5]. In contrast, the yeast Saccharomyces boulardii, when added to mesalazine, has been shown to maintain remission of inactive Crohn's disease more effectively than mesalazine alone [6]. On the other hand, the probiotic mixture named VSL #3, although sometimes providing disappointing results in experimental models, has been shown in several clinical trials to prevent recurrence of pouchitis [2]. On the whole, it appears that each single probiotic agent has to be separately tested in clinical practice, time-consuming and irritating though this process can be. As for prebiotics, the scenario is even more confusing due to the scarcity of well-performed clinical studies. Hence it is almost impossible to draw definite conclusions about the potential role of combinations of pro- and prebiotics (synbiotics) in intestinal disorders as a whole and in IBD in particular. As aptly observed by Damaskos and Kolios [2], mixtures expected to act synergistically might fail to exhibit the predicted results, and so many combinations of probiotics and prebiotics can be postulated that the number of trials to be performed is overwhelming. In conclusion, there is a sound rationale for the use of probiotics in the treatment of IBD. From the published studies some probiotics (S. boulardii, VSL #3) appear to be clinically effective, whereas others either do not offer any substantial benefit or are still to be evaluated in controlled trials. Prebiotics can enhance the efficacy of probiotics alone, but the quality and quantity of the studies available so far are too limited to identify the most effective synbiotic combinations.

Systematic review: nutritional therapy in paediatric Crohn’s disease

At least 25% of individuals diagnosed with Crohn's disease (CD) have onset of disease in childhood. Almost all children with CD have nutritional impairments, such as weight loss or stunting, at diagnosis or subsequently. Nutritional therapy (exclusive enteral nutrition) is established as a valid and effective treatment in paediatric CD. The advantages of this approach are induction of remission and control of inflammatory changes, mucosal healing, positive benefits to growth and overall nutritional status, and avoidance of other medical therapies. To provide a comprehensive up-to-date review of the roles of nutritional therapy in CD and of the data supporting this therapy. A search of PubMed was performed with search terms 'enteral nutrition', 'nutritional therapy', 'Crohn disease' and 'children'. Relevant articles were selected from this search. In addition, the reference lists of available articles were reviewed for further relevant articles. Nutritional therapy offers numerous benefits in the management of CD. Recent work has begun to elucidate the likely mechanisms of this therapy. These include direct mucosal anti-inflammatory effects and alteration of intestinal microflora. Further studies are required to define longer-term effects of nutritional therapy in patients with CD.

Acne vulgaris: Nutritional factors may be influencing psychological sequelae

Acne vulgaris is a distressing skin condition which can carry with it significant psychological disability. Patients with acne are more likely to experience anger and are at increased risk of depression, anxiety, suicidal ideation. Certain nutrients which have been implicated as influencing the pathophysiology of acne have also been identified as important mediators of human cognition, behavior and emotions. Zinc, folic acid, selenium, chromium and omega-3 fatty acids are all examples of nutrients which have been shown to influence depression, anger and/or anxiety. These same nutrients, along with systemic oxidative stress and an altered intestinal microflora have been implicated in acne vulgaris. It is our contention that certain nutritional factors, a weakened antioxidant defense system and altered intestinal microflora may interplay to increase the risk of psychological sequelae in acne vulgaris.

Nutrition and Nutritional Management of Crohns Disease in Children and Adolescents

Crohns disease (CD) is a life-long inflammatory process affecting any segment of the gastrointestinal tract. This condition most often presents in childhood and adolescence and almost universally impacts adversely upon the nutritional state of the patient. Weight loss is a common presenting feature and potential long-term adverse outcomes include malnutrition, anaemia, osteopaenia and impaired linear growth. Understanding the nutritional aspects of this disease is especially important in growing children and adolescents entering and advancing through puberty. In addition, a nutritional approach to the management of CD is now well established as a valid and effective treatment to induce and maintain disease remission. The mechanisms of this therapy are beginning to be defined, and include direct antiinflammatory effects and alteration of intestinal microflora. This review focuses upon the role of nutritional therapy in the management of CD in children and adolescents in the context of a comprehensive nutritional approach to managing individuals with this chronic condition. Keywords: Nutrition, exclusive enteral nutrition, children, Crohn's disease, inflammatory bowel disease

Prenatal Blockage of Lymphotoxin β Receptor and TNF Receptor p55 Signaling Cascade Resulted in the Acceleration of Tissue Genesis for Isolated Lymphoid Follicles in the Large Intestine

Signaling by lymphotoxin (LT) and TNF is essential for the organogenesis of secondary lymphoid tissues in systemic and mucosal compartments. In this study, we demonstrated that the progeny of mice treated with fusion protein of LTbetaR and IgGFc (LTbetaR-Ig) or LTbetaR-Ig plus TNFR55-Ig (double Ig) showed significantly increased numbers of isolated lymphoid follicles (ILF) in the large intestine. Interestingly, double Ig treatment accelerated the maturation of large intestinal ILF. Three-week-old progeny of double Ig-treated mice showed increased numbers of ILF in the large intestine, but not in the small intestine. Furthermore, alteration of intestinal microflora by feeding of antibiotic water did not affect the increased numbers of ILF in the large intestine of double Ig-treated mice. Most interestingly, mice that developed numerous ILF also had increased levels of activation-induced cytidine deaminase expression and numbers of IgA-expressing cells in the lamina propria of the large intestine. Taken together, these results suggest that ILF formation in the large intestine is accelerated by blockage of LTbetaR and TNFR55 signals in utero, and ILF, like colonic patches, might play a role in the induction of IgA response in the large intestine.

Stress-induced alterations in intestinal microflora

Stress-induced alterations in intestinal microflora

Stress-Induced Alterations in Intestinal Microflora

Along with other endogenous and exogenous factors which may interfere in the regulation of various pathways that control the intestinal microflora, physical and psychological stress seem to play a crucial role. In order to estimate the influence of psychological stress on the intestinal microflora composition, repeated restraint stress was used as a stress paradigm. Faecal indicator bacteria (aerobic and anaerobic) were used to assess the microbiological profile of the intestinal flora. Faecal samples were collected from adult male Wistar rats (Kuo/Ioa/rr) before and after repeated restraint stress. Serial dilutions were performed in Ringer solution followed by spreading on MacConkey agar that had been incubated at 37C overnight. An aliquot of each solution was heated at 75C for 10 min, followed by spreading in lactose-sulfite (LS) broth. Numbers of Clostridium perfringens were estimated by performing decimal dilutions in the LS broth that had been incubated in a water bath at 46C overnight. Characteristic colonies of Escherichia coli were counted and identified using the API 20E System. Numbers of C. perfringens were estimated and compared to those of E. coli . Higher numbers of vegetative forms of the anaerobic bacterial indicator C. perfringens were found in stress-exposed animals as compared with controls and with pre-stress conditions. The end of the stress exposure found the numbers of C. perfringens back to initial levels or even below. Key words: stress, intestinal microflora, Clostridium perfringen s, rat.

Inhibitory Effects of Bifidobacterium longum on Experimental Ulcerative Colitis Induced in Mice by Synthetic Dextran Sulfate Sodium

Background/Aims: The relationship between alterations in intestinal microflora and ulcerative colitis is still not clear. Whether improvement in bacterial populations might be a new strategy for prevention or treatment needs to be tested. Methods: Ulcerative colitis was induced in mice by oral administration of synthetic dextran sulfate sodium (molecular weight 54,000). Inhibitory effects of concomitant treatment with Bifidobacterium longum were assessed in terms of total colon length and severity of histological changes. In addition, changes of microflora and short-chain fatty acids were tested in fecal samples and compared before and after treatment. Results: Administration of B. longum significantly inhibited both shortening of total colon length and the severity of ulcerative colitis compared to controls. It was confirmed that the administered B. longum resided in the gut and blocked the decrease of lactobacilli in fecal samples in mice with dextran sulfate sodium-induced colitis. Conclusions: Oral administration of B. longum exerts marked inhibitory effects on ulcerative colitis in mice.

Alterations in intestinal microflora, faecal bile acids and short chain fatty acids in dextran sulphate sodium-induced experimental acute colitis in rats.

The physiological effects on faecal bile acids and short chain fatty acids (SCFAs) or intestinal microflora in dextran sulphate sodium (DSS)-induced colitis remain unknown and are an area of interest DESIGN ALTERATIONS: of these parameters in DSS-induced colitis in rats were evaluated. Male Sprague-Dawley rats (n = 10) were given a 3% DSS aqueous solution orally for 7 days. The concentrations of bile acids and SCFAs in the faeces were measured using gas chromatography and high-performance liquid chromatography. Intestinal microflora, especially anaerobes, were investigated by microbiological methods. On day 7, the concentrations of lithocholic acid and alpha-muricholic acid were significantly decreased and that of cholic acid was significantly increased. There was a strong correlation between the concentration of cholic acid and the macroscopic area of damaged tissue in the colon (R = 0.74, P < 0.05). With respect to SCFAs, DSS administration significantly decreased the concentrations of acetic acid and n-butyric acid. There was also some correlation between the concentration of acetic acid and macroscopic damaged area in the colon (R = -0.60, P = 0.07). Bacteriological studies revealed significantly decreased eubacteria, bifidobacteria and total anaerobes after the administration of DSS. In contrast, lactobacilli were significantly increased. With the progression of DSS-induced colitis, faecal bile acids, SCFAs and intestinal microflora were altered. It is possible that these alterations contribute in part to the progression of DSS-induced colitis.

Biotherapeutic agents and disease in infants.

Human milk contains many factors that act synergistically or with redundancy in protecting suckling infants from infectious diseases. The rigorous application of the scientific method has shown significant beneficial effects of these specific factors. The beneficial effects of biotherapeutic agents, including prebiotics and probiotics, on the alteration of intestinal microflora and modulation of the local and systemic immune response of infants have been shown. The beneficial effects of these compounds on preventing diarrhea and possibly other infectious diseases in infants serves as a model for the development and use of biotherapeutic agents to treat and prevent infectious diseases in persons of all ages.

Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome

OBJECTIVE: The influence of the gastrointestinal (GI) microflora in patients with irritable bowel syndrome (IBS) has not been clearly elucidated. This study was undertaken to see if patients with IBS have an imbalance in their normal colonic flora, as some bacterial taxa are more prone to gas production than others. We also wanted to study whether the flora could be altered by exogenous supplementation. In a previous study we have characterized the mucosa-associated lactobacilli in healthy individuals and found some strains with good colonizing ability. Upon colonization, they seemed to reduce gas formation. METHODS: The study comprised 60 patients with IBS and a normal colonoscopy or barium enema. Patients fulfilling the Rome criteria, without a history of malabsorption, and with normal blood tests underwent a sigmoidoscopy with biopsy. They were randomized into two groups, one receiving 400 ml per day of a rose-hip drink containing 5 × 10 7 cfu/ml of Lactobacillus plantarum (DSM 9843) and 0.009 g/ml oat flour, and the other group receiving a plain rose-hip drink, comparable in color, texture, and taste. The administration lasted for 4 wk. The patients recorded their own GI function, starting 2 wk before the study and continuing throughout the study period. Twelve months after the end of the study all patients were asked to complete the same questionnaire regarding their symptomatology as at the start of the study. RESULTS: All patients tolerated the products well. The patients receiving Lb. plantarum had these bacteria on rectal biopsies. There were no major changes of Enterobacteriaceae in either group, before or after the study, but the Enterococci increased in the placebo group and remained unchanged in the test group. Flatulence was rapidly and significantly reduced in the test group compared with the placebo group (number of days with abundant gas production, test group 6.5 before, 3.1 after vs 7.4 before and 5.6 after for the placebo group). Abdominal pain was reduced in both groups. At the 12-month follow-up, patients in the test group maintained a better overall GI function than control patients. There was no difference between the groups regarding bloating. Fifty-nine percent of the test group patients had a continuous intake of fermented products, whereas the corresponding figure for the control patients was 73%. CONCLUSIONS: The results of the study indicate that the administration of Lb. plantarum with known probiotic properties decreased pain and flatulence in patients with IBS. The fiber content of the test solution was minimal and it is unlikely that the fiber content could have had any effect. This type of probiotic therapy warrants further studies in IBS patients.

Increased bacterial urease activity in faeces in juvenile chronic arthritis: evidence of altered intestinal microflora?

The intestinal microflora was indirectly evaluated in juvenile chronic arthritis (JCA) by analysing enzyme activities--urease, beta-glucosidase and beta-glucuronidase--in faeces. In 18 out of 26 JCA patients, the illness had been diagnosed during the past year. The control group was composed of eight age-matched control patients and 18 family members of JCA patients (3-36 yr). The mean [95% confidence interval (CI)] urease activity, but not the activities of beta-glucosidase and beta-glucuronidase, in faeces from the JCA group differed from that in the control group: 32.3 (26.6-38.1) nmol/min/mg protein vs 24.0 (16.8-31.6), P = 0.07. The difference was more marked in a comparison of JCA patients with family members (P = 0.03). In a subgroup of subjects, the effect of 10 days oral bacteriotherapy with Lactobacillus GG on faecal enzyme activities was then investigated (n = 8 JCA patients, n = 8 control patients). This short-term oral bacteriotherapy reduced the increased urease activity in faeces of JCA patients. Keeping in mind the small number of subjects, it may be inferred from the present results that the increased urease activity in JCA is specific for the disease, suggesting altered intestinal microflora in JCA.

Adverse effects of macrolide antibacterials.

The renewed interest in macrolide antibacterials with expanded indications for clinical use, as well as their markedly increased usage, justifies the continuous search for new compounds designed to offer the patient not only enhanced bioavailability but also a reduced incidence of adverse effects. Macrolides are an old and well established class of antimicrobial agents that account for 10 to 15% of the worldwide oral antibiotic market. Macrolides are considered to be one of the safest anti-infective groups in clinical use, with severe adverse reactions being rare. Newer products with improved features have recently been discovered and developed, maintaining or significantly expanding the role of macrolides in the management of infection. This review deals with the tolerability of the clinically available macrolide antibacterials. With the exception of drug interactions, adverse effects have been analysed during the last 40 years in many thousands of adult and paediatric patients. Recently developed derivatives have been compared with the older compounds, and the expected and well assessed adverse effects have been set apart from those which are unusual, very rare or questionable. Gastrointestinal reactions represent the most frequent disturbance, occurring in 15 to 20% of patients on erythromycins and in 5% or fewer patients treated with some recently developed macrolide derivatives that seldom or never induce endogenous release of motilin, such as roxithromycin, clarithromycin, dirithromycin, azithromycin and rikamycin (rokitamycin). Except for troleandomycin and some erythromycins administered at high dose and for long periods of time, the hepatotoxic potential of macrolides, which rarely or never form nitrosoalkanes, is low for josamycin, midecamycin, miocamycin, flurithromycin, clarithromycin and roxithromycin; it is negligible or absent for spiramycin, rikamycin, dirithromycin and azithromycin. Transient deafness and allergic reactions to macrolide antibacterials are highly unusual and have definitely been shown to be more common following treatment with the erythromycins than with the recently developed 14-, 15- and 16-membered macrolides. There have been case reports in the literature of 51 patients during the last 30 years who experienced uncommon or dubious adverse effects after treatment with older compounds and in which there appears to be strong evidence of a causal relationship with the drug. Only 3 cases had an unfavourable outcome, and these were patients administered erythromycin lactobionate intravenously too rapidly or at high dose. Targets of these occasional reactions are generally the heart, liver and central nervous system. Other unusual organ pathologies are related to immunomediated disorders more than to primary parenchymal toxicity, or to the rarely serious consequences of macrolide-induced alterations in intestinal microflora.(ABSTRACT TRUNCATED AT 400 WORDS)

Alterations of intestinal microflora by antibiotics

The effects of intragastric antibiotics in rats were examined on fecal microflora and excretion and through transit time and cecocolonic myoelectric activity. A solution of nonabsorbable antibiotics infused into the stomach for 20 days had a dramatic effect on the quantity, composition, and bacterial content of rat feces. Both the dry weight and the water content of feces were increased. The amount of short-chain fatty acids in the feces was dramatically lowered. However, neither total nor cecocolonic transit time of solids was affected. The cyclic organization of cecocolonic myoelectric activity was altered by antibiotic treatment, and the motility index, ie, the quantity of myoelectric activity recorded on the colon, progressively increased. An infusion of short-chain fatty acids modified this motor pattern but did not restore activity to a level comparable to that of control animals. In conclusion, intragastric antibiotics dramatically reduced intestinal microflora and increased fecal excretion of dry matter and water but did not affect the transit time of solid gut contents, although they did influence cecocolonic motility.