Health benefits of probiotics: are mixtures more effective than single strains?

PURPOSE: Most studies on probiotics utilise single strains, sometimes incorporated into yoghurts. There are fewer studies on efficacy of mixtures of probiotic strains. This review examines the evidence that (a) probiotic mixtures are beneficial for a range of health-related outcomes and (b) mixtures are more or less effective than their component strains administered separately. RESULTS: Mixtures of probiotics had beneficial effects on the end points including irritable bowel syndrome and gut function, diarrhoea, atopic disease, immune function and respiratory tract infections, gut microbiota modulation, inflammatory bowel disease and treatment of Helicobacter pylori infection. However, only 16 studies compared the effect of a mixture with that of its component strains separately, although in 12 cases (75%), the mixture was more effective. CONCLUSION: Probiotic mixtures appear to be effective against a wide range of end points. Based on a limited number of studies, multi-strain probiotics appear to show greater efficacy than single strains, including strains that are components of the mixtures themselves. However, whether this is due to synergistic interactions between strains or a consequence of the higher probiotic dose used in some studies is at present unclear.

Current level of consensus on probiotic science: report of an expert meeting, London, 23 November 2009

The present paper summarizes  the consensus views of a group of 9 European clinicians and scientists on the current state of scientific knowledge on probiotics, covering those areas where there is substantial evidence for beneficial effects and those  where the evidence base is poor or inconsistent. There was general agreement that probiotic effects were species and often strain specific. The experts agreed  that some probiotics were effective in reducing the incidence and duration of rotavirus diarrhoea in infants, antibiotic-associated diarrhoea in adults and, for certain probiotics, Clostridium difficile infections. Some probiotics are associated with symptomatic improvements in irritable bowel syndrome and alleviation of digestive discomfort. Probiotics can reduce the frequency and severity of necrotizing enterocolitis in premature infants and have been shown to regulate intestinal immunity.  Several other clinical effects of probiotics, including their role in inflammatory bowel disease, atopic dermatitis, respiratory or genito-urinary infections or H.pylori adjuvant treatment were thought promising but inconsistent.

Prebiotics and the health benefits of fiber: current regulatory status, future research, and goals.

First defined in the mid-1990s, prebiotics, which alter the composition and activity of gastrointestinal (GI) microbiota to improve health and well-being, have generated scientific and consumer interest and regulatory debate. The Life Sciences Research Organization, Inc. (LSRO) held a workshop, Prebiotics and the Health Benefits of Fiber: Future Research and Goals, in February 2011 to assess the current state of the science and the international regulatory environment for prebiotics, identify research gaps, and create a strategy for future research. A developing body of evidence supports a role for prebiotics in reducing the risk and severity of GI infection and inflammation, including diarrhea, inflammatory bowel disease, and ulcerative colitis as well as bowel function disorders, including irritable bowel syndrome. Prebiotics also increase the bioavailability and uptake of minerals and data suggest that they reduce the risk of obesity by promoting satiety and weight loss. Additional research is needed to define the relationship between the consumption of different prebiotics and improvement of human health. New information derived from the characterization of the composition and function of different prebiotics as well as the interactions among and between gut microbiota and the human host would improve our understanding of the effects of prebiotics on health and disease and could assist in surmounting regulatory issues related to prebiotic use.

Mechanisms of protease-activated receptor 2-evoked hyperexcitability of nociceptive neurons innervating the mouse colon

Agonists of protease-activated receptor 2 (PAR(2)) evoke hyperexcitability of dorsal root ganglia (DRG) neurons by unknown mechanisms. We examined the cellular mechanisms underlying PAR(2)-evoked hyperexcitability of mouse colonic DRG neurons to determine their potential role in pain syndromes such as visceral hyperalgesia. Colonic DRG neurons were identified by injecting Fast Blue and DiI retrograde tracers into the mouse colon. Using immunofluorescence, we found that DiI-labelled neurons contained PAR(2) immunoreactivity, confirming the presence of receptors on colonic neurons. Whole-cell current-clamp recordings of acutely dissociated neurons demonstrated that PAR(2) activation with a brief application (3 min) of PAR(2) agonists, SLIGRL-NH(2) and trypsin, evoked sustained depolarizations (up to 60 min) which were associated with increased input resistance and a marked reduction in rheobase (50% at 30 min). In voltage clamp, SLIGRL-NH(2) markedly suppressed delayed rectifier I(K) currents (55% at 10 min), but had no effect on the transient I(A) current or TTX-resistant Na(+) currents. In whole-cell current-clamp recordings, the sustained excitability evoked by PAR(2) activation was blocked by the PKC inhibitor, calphostin, and the ERK(1/2) inhibitor PD98059. Studies of ERK(1/2) phosphorylation using confocal microscopy demonstrated that SLIGRL-NH(2) increased levels of immunoreactive pERK(1/2) in DRG neurons, particularly in proximity to the plasma membrane. Thus, activation of PAR(2) receptors on colonic nociceptive neurons causes sustained hyperexcitability that is related, at least in part, to suppression of delayed rectifier I(K) currents. Both PKC and ERK(1/2) mediate the PAR(2)-induced hyperexcitability. These studies describe a novel mechanism of sensitization of colonic nociceptive neurons that may be implicated in conditions of visceral hyperalgesia such as irritable bowel syndrome.

Structural changes in the epithelium of the small intestine and immune cell infiltration of enteric ganglia following acute mucosal damage and local inflammation

An acute enteritis is commonly followed by intestinal neuromuscular dysfunction, including prolonged hyperexcitability of enteric neurons. Such motility disorders are associated with maintained increases in immune cells adjacent to enteric ganglia and in the mucosa. However, whether the commonly used animal model, trinitrobenzene sulphonate (TNBS)-induced enteritis, causes histological and immune cell changes similar to human enteric neuropathies is not clear. We have made a detailed study of the mucosal damage and repair and immune cell invasion following intralumenal administration of TNBS. Intestines from untreated, sham-operated and TNBS-treated animals were examined at 3 h to 56 days. At 3 h, the mucosal surface was completely ablated, by 6 h an epithelial covering was substantially restored and by 1 day there was full re-epithelialisation. The lumenal epithelium developed from a squamous cell covering to a fully differentiated columnar epithelium with mature villi at about 7 days. Prominent phagocytic activity of enterocytes occurred at 1-7 days. A surge of eosinophils and T lymphocytes associated with the enteric nerve ganglia occurred at 3 h to 3 days. However, elevated immune cell numbers occurred in the lamina propria of the mucosa until 56 days, when eosinophils were still three times normal. We conclude that the disruption of the mucosal surface that causes TNBS-induced ileitis is brief, a little more than 6 h, and causes a transient immune cell surge adjacent to enteric ganglia. This is much briefer than the enteric neuropathy that ensues. Ongoing mucosal inflammatory reaction may contribute to the persistence of enteric neuropathy.

Síndrome do intestino irritável

Irritable bowel syndrome is a high prevalent functional disorder. Its diagnosis is based in symptoms and the Rome Criteria. The treatment takes in account psychosocial and biologic factors. The therapeutic measures aim to correct the predominant symptoms: constipation, diarrhea and abdominal pain.

Impatto di rifaximina sul microbiota intestinale: selezione di bifidobatteri antibiotico resistenti

The ideal approach for the long term treatment of intestinal disorders, such as inflammatory bowel disease (IBD), is represented by a safe and well tolerated therapy able to reduce mucosal inflammation and maintain homeostasis of the intestinal microbiota. A combined therapy with antimicrobial agents, to reduce antigenic load, and immunomodulators, to ameliorate the dysregulated responses, followed by probiotic supplementation has been proposed. Because of the complementary mechanisms of action of antibiotics and probiotics, a combined therapeutic approach would give advantages in terms of enlargement of the antimicrobial spectrum, due to the barrier effect of probiotic bacteria, and limitation of some side effects of traditional chemiotherapy (i.e. indiscriminate decrease of aggressive and protective intestinal bacteria, altered absorption of nutrient elements, allergic and inflammatory reactions). Rifaximin (4-deoxy-4’-methylpyrido[1’,2’-1,2]imidazo[5,4-c]rifamycin SV) is a product of synthesis experiments designed to modify the parent compound, rifamycin, in order to achieve low gastrointestinal absorption while retaining good antibacterial activity. Both experimental and clinical pharmacology clearly show that this compound is a non systemic antibiotic with a broad spectrum of antibacterial action, covering Gram-positive and Gram-negative organisms, both aerobes and anaerobes. Being virtually non absorbed, its bioavailability within the gastrointestinal tract is rather high with intraluminal and faecal drug concentrations that largely exceed the MIC values observed in vitro against a wide range of pathogenic microorganisms. The gastrointestinal tract represents therefore the primary therapeutic target and gastrointestinal infections the main indication. The little value of rifaximin outside the enteric area minimizes both antimicrobial resistance and systemic adverse events. Fermented dairy products enriched with probiotic bacteria have developed into one of the most successful categories of functional foods. Probiotics are defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host” (FAO/WHO, 2002), and mainly include Lactobacillus and Bifidobacterium species. Probiotic bacteria exert a direct effect on the intestinal microbiota of the host and contribute to organoleptic, rheological and nutritional properties of food. Administration of pharmaceutical probiotic formula has been associated with therapeutic effects in treatment of diarrhoea, constipation, flatulence, enteropathogens colonization, gastroenteritis, hypercholesterolemia, IBD, such as ulcerative colitis (UC), Crohn’s disease, pouchitis and irritable bowel syndrome. Prerequisites for probiotics are to be effective and safe. The characteristics of an effective probiotic for gastrointestinal tract disorders are tolerance to upper gastrointestinal environment (resistance to digestion by enteric or pancreatic enzymes, gastric acid and bile), adhesion on intestinal surface to lengthen the retention time, ability to prevent the adherence, establishment and/or replication of pathogens, production of antimicrobial substances, degradation of toxic catabolites by bacterial detoxifying enzymatic activities, and modulation of the host immune responses. This study was carried out using a validated three-stage fermentative continuous system and it is aimed to investigate the effect of rifaximin on the colonic microbial flora of a healthy individual, in terms of bacterial composition and production of fermentative metabolic end products. Moreover, this is the first study that investigates in vitro the impact of the simultaneous administration of the antibiotic rifaximin and the probiotic B. lactis BI07 on the intestinal microbiota. Bacterial groups of interest were evaluated using culture-based methods and molecular culture-independent techniques (FISH, PCR-DGGE). Metabolic outputs in terms of SCFA profiles were determined by HPLC analysis. Collected data demonstrated that rifaximin as well as antibiotic and probiotic treatment did not change drastically the intestinal microflora, whereas bacteria belonging to Bifidobacterium and Lactobacillus significantly increase over the course of the treatment, suggesting a spontaneous upsurge of rifaximin resistance. These results are in agreement with a previous study, in which it has been demonstrated that rifaximin administration in patients with UC, affects the host with minor variations of the intestinal microflora, and that the microbiota is restored over a wash-out period. In particular, several Bifidobacterium rifaximin resistant mutants could be isolated during the antibiotic treatment, but they disappeared after the antibiotic suspension. Furthermore, bacteria belonging to Atopobium spp. and E. rectale/Clostridium cluster XIVa increased significantly after rifaximin and probiotic treatment. Atopobium genus and E. rectale/Clostridium cluster XIVa are saccharolytic, butyrate-producing bacteria, and for these characteristics they are widely considered health-promoting microorganisms. The absence of major variations in the intestinal microflora of a healthy individual and the significant increase in probiotic and health-promoting bacteria concentrations support the rationale of the administration of rifaximin as efficacious and non-dysbiosis promoting therapy and suggest the efficacy of an antibiotic/probiotic combined treatment in several gut pathologies, such as IBD. To assess the use of an antibiotic/probiotic combination for clinical management of intestinal disorders, genetic, proteomic and physiologic approaches were employed to elucidate molecular mechanisms determining rifaximin resistance in Bifidobacterium, and the expected interactions occurring in the gut between these bacteria and the drug. The ability of an antimicrobial agent to select resistance is a relevant factor that affects its usefulness and may diminish its useful life. Rifaximin resistance phenotype was easily acquired by all bifidobacteria analyzed [type strains of the most representative intestinal bifidobacterial species (B. infantis, B. breve, B. longum, B. adolescentis and B. bifidum) and three bifidobacteria included in a pharmaceutical probiotic preparation (B. lactis BI07, B. breve BBSF and B. longum BL04)] and persisted for more than 400 bacterial generations in the absence of selective pressure. Exclusion of any reversion phenomenon suggested two hypotheses: (i) stable and immobile genetic elements encode resistance; (ii) the drug moiety does not act as an inducer of the resistance phenotype, but enables selection of resistant mutants. Since point mutations in rpoB have been indicated as representing the principal factor determining rifampicin resistance in E. coli and M. tuberculosis, whether a similar mechanism also occurs in Bifidobacterium was verified. The analysis of a 129 bp rpoB core region of several wild-type and resistant bifidobacteria revealed five different types of miss-sense mutations in codons 513, 516, 522 and 529. Position 529 was a novel mutation site, not previously described, and position 522 appeared interesting for both the double point substitutions and the heterogeneous profile of nucleotide changes. The sequence heterogeneity of codon 522 in Bifidobacterium leads to hypothesize an indirect role of its encoded amino acid in the binding with the rifaximin moiety. These results demonstrated the chromosomal nature of rifaximin resistance in Bifidobacterium, minimizing risk factors for horizontal transmission of resistance elements between intestinal microbial species. Further proteomic and physiologic investigations were carried out using B. lactis BI07, component of a pharmaceutical probiotic preparation, as a model strain. The choice of this strain was determined based on the following elements: (i) B. lactis BI07 is able to survive and persist in the gut; (ii) a proteomic overview of this strain has been recently reported. The involvement of metabolic changes associated with rifaximin resistance was investigated by proteomic analysis performed with two-dimensional electrophoresis and mass spectrometry. Comparative proteomic mapping of BI07-wt and BI07-res revealed that most differences in protein expression patterns were genetically encoded rather than induced by antibiotic exposure. In particular, rifaximin resistance phenotype was characterized by increased expression levels of stress proteins. Overexpression of stress proteins was expected, as they represent a common non specific response by bacteria when stimulated by different shock conditions, including exposure to toxic agents like heavy metals, oxidants, acids, bile salts and antibiotics. Also, positive transcription regulators were found to be overexpressed in BI07-res, suggesting that bacteria could activate compensatory mechanisms to assist the transcription process in the presence of RNA polymerase inhibitors. Other differences in expression profiles were related to proteins involved in central metabolism; these modifications suggest metabolic disadvantages of resistant mutants in comparison with sensitive bifidobacteria in the gut environment, without selective pressure, explaining their disappearance from faeces of patients with UC after interruption of antibiotic treatment. The differences observed between BI07-wt e BI07-res proteomic patterns, as well as the high frequency of silent mutations reported for resistant mutants of Bifidobacterium could be the consequences of an increased mutation rate, mechanism which may lead to persistence of resistant bacteria in the population. However, the in vivo disappearance of resistant mutants in absence of selective pressure, allows excluding the upsurge of compensatory mutations without loss of resistance. Furthermore, the proteomic characterization of the resistant phenotype suggests that rifaximin resistance is associated with a reduced bacterial fitness in B. lactis BI07-res, supporting the hypothesis of a biological cost of antibiotic resistance in Bifidobacterium. The hypothesis of rifaximin inactivation by bacterial enzymatic activities was verified by using liquid chromatography coupled with tandem mass spectrometry. Neither chemical modifications nor degradation derivatives of the rifaximin moiety were detected. The exclusion of a biodegradation pattern for the drug was further supported by the quantitative recovery in BI07-res culture fractions of the total rifaximin amount (100 μg/ml) added to the culture medium. To confirm the main role of the mutation on the β chain of RNA polymerase in rifaximin resistance acquisition, transcription activity of crude enzymatic extracts of BI07-res cells was evaluated. Although the inhibition effects of rifaximin on in vitro transcription were definitely higher for BI07-wt than for BI07-res, a partial resistance of the mutated RNA polymerase at rifaximin concentrations > 10 μg/ml was supposed, on the basis of the calculated differences in inhibition percentages between BI07-wt and BI07-res. By considering the resistance of entire BI07-res cells to rifaximin concentrations > 100 μg/ml, supplementary resistance mechanisms may take place in vivo. A barrier for the rifaximin uptake in BI07-res cells was suggested in this study, on the basis of the major portion of the antibiotic found to be bound to the cellular pellet respect to the portion recovered in the cellular lysate. Related to this finding, a resistance mechanism involving changes of membrane permeability was supposed. A previous study supports this hypothesis, demonstrating the involvement of surface properties and permeability in natural resistance to rifampicin in mycobacteria, isolated from cases of human infection, which possessed a rifampicin-susceptible RNA polymerase. To understand the mechanism of membrane barrier, variations in percentage of saturated and unsaturated FAs and their methylation products in BI07-wt and BI07-res membranes were investigated. While saturated FAs confer rigidity to membrane and resistance to stress agents, such as antibiotics, a high level of lipid unsaturation is associated with high fluidity and susceptibility to stresses. Thus, the higher percentage of saturated FAs during the stationary phase of BI07-res could represent a defence mechanism of mutant cells to prevent the antibiotic uptake. Furthermore, the increase of CFAs such as dihydrosterculic acid during the stationary phase of BI07-res suggests that this CFA could be more suitable than its isomer lactobacillic acid to interact with and prevent the penetration of exogenous molecules including rifaximin. Finally, the impact of rifaximin on immune regulatory functions of the gut was evaluated. It has been suggested a potential anti-inflammatory effect of rifaximin, with reduced secretion of IFN-γ in a rodent model of colitis. Analogously, it has been reported a significant decrease in IL-8, MCP-1, MCP-3 e IL-10 levels in patients affected by pouchitis, treated with a combined therapy of rifaximin and ciprofloxacin. Since rifaximin enables in vivo and in vitro selection of Bifidobacterium resistant mutants with high frequency, the immunomodulation activities of rifaximin associated with a B. lactis resistant mutant were also taken into account. Data obtained from PBMC stimulation experiments suggest the following conclusions: (i) rifaximin does not exert any effect on production of IL-1β, IL-6 and IL-10, whereas it weakly stimulates production of TNF-α; (ii) B. lactis appears as a good inducer of IL-1β, IL-6 and TNF-α; (iii) combination of BI07-res and rifaximin exhibits a lower stimulation effect than BI07-res alone, especially for IL-6. These results confirm the potential anti-inflammatory effect of rifaximin, and are in agreement with several studies that report a transient pro-inflammatory response associated with probiotic administration. The understanding of the molecular factors determining rifaximin resistance in the genus Bifidobacterium assumes an applicative significance at pharmaceutical and medical level, as it represents the scientific basis to justify the simultaneous use of the antibiotic rifaximin and probiotic bifidobacteria in the clinical treatment of intestinal disorders.

Mechanosensitivity in the myenteric plexus of the guinea pig ileum

The enteric nervous system regulates autonomously from the central nervous system all the reflex pathways that control blood flow, motility, water and electrolyte transport and acid secretion. The ability of the gut to function in isolation is one of the most intriguing phenomenons in neurogastroenterology. This requires coding of sensory stimuli by cells in the gut wall. Enteric neurons are prominent candidates to relay mechanosensitivity. Surprisingly, the identity of mechanosensitive neurons in the enteric nervous system as well as the appropriate stimulus modality is unknown despite the evidence that enteric neurons respond to sustained distension. Objectives: The aim of our study was to record from mechanosensitive neurons using physiological stimulus modalities. Identification of sensory neurons is of central importance to understand sensory transmission under normal conditions and in gut diseases associated with sensorimotor dysfunctions, such as Irritable Bowel Syndrome. Only then it will be possible to identify novel targets that help to normalise sensory functions. Methods: We used guinea-pig ileum myenteric plexus preparations and recorded responses of all neurons in a given ganglion with a fast neuroimaging technique based on voltage sensitive dyes. To evoke a mechanical response we used two different kinds of stimuli: firstly we applied a local mechanical distortion of the ganglion surface with von Frey hair. Secondarily we mimic the ganglia deformation during physiological movements of myenteric ganglia in a freely contracting ileal preparation. We were able to reliably and reproducibly mimic this distortion by intraganglionic injections of small volumes of oxygenated and buffered Krebs solution using stimulus parameters that correspond to single contractions. We also performed in every ganglion tested, electrical stimulations to evoke fast excitatory postsynaptic potentials. Immunohistochemistry reactions were done with antibodies against Calbindin and NeuN, considered markers for sensory neurons. Results: Recordings were performed in 46 ganglia from 31 guinea pigs. In every ganglion tested we found from 1 to 21 (from 3% to 62%) responding cells with a median value of 7 (24% of the total number of neurons). The response consisted of an almost instantaneous spike discharge that showed adaptation. The median value of the action potential frequency in the responding neurons was 2.0 Hz, with a recording time of 1255 ms. The spike discharge lasted for 302 ± 231 ms and occurred only during the initial deformation phase. During sustained deformation no spike discharge was observed. The response was reproducible and was a direct activation of the enteric neurons since it remained after synaptic blockade with hexamethonium or ω-conotoxin and after long time perfusion with capsaicin. Muscle tone appears not to be required for activation of mechanosensory neurons. Mechanosensory neurons showed a response to mechanical stimulation related to the stimulus strength. All mechanosensory neurons received fast synaptic inputs. There was no correlation between mechanosensitivity and Calbindin-IR and NeuN-IR (44% of mechanosensitive neurones Calb-IR-/NeuN-IR-). Conclusions: We identified mechanosensitive neurons in the myenteric plexus of the guinea pig ileum which responded to brief deformation. These cells appear to be rapidly accommodating neurons which respond to dynamic change. All mechanosensitive neurons received fast synaptic input suggesting that their activity can be highly modulated by other neurons and hence there is a low stimulus fidelity which allows adjusting the gain in a sensory network. Mechanosensitivity appears to be a common feature of many enteric neurons belonging to different functional classes. This supports the existence of multifunctional enteric neurons which may fulfil sensory, integrative and motor functions.

Multimodal therapy of functional gastrointestinal disorders

A multimodal approach is state-of-the art for effective treatment of functional gastrointestinal disorders (FGD) like irritable bowel syndrome and functional dyspepsia. Based on the now established view that the pathogenesis of FGD is multicausal, evidence-based therapeutic options comprise education about the nature of the disorder, dietary modifications, relaxation techniques, behavioral changes, and pharmacological treatments. These therapies are variously combined depending on the severity of the FGD and the individual needs of the patient. Our overview portrays the options for the therapy of FGD and proposes that these are best provided by an interdisciplinary team of primary care physicians, gastroenterologists, and psychosomatic medicine specialists.

[Pathogenesis of functional gastrointestinal disorders - an interdisciplinary perspective]

Functional gastrointestinal disorders (FGD) are highly prevalent worldwide. Recent research demonstrates that complex and interacting biological and behavioral mechanisms contribute particularly to the pathogenesis of irritable bowel syndrome and functional dyspepsia. Dysregulation of the enteral, neuroenteric, visceral-autonomic, and central nervous systems are important biological contributors, whereas the psychological state of a patient may evidently modulate aspects related to biological stress reactivity and somatic perception both playing a role in the clinical manifestation of FGD. Our overview clearly shows that an interdisciplinary perspective of the pathogenesis of FGD may best serve clinicians and patients.

[Abdominal pain - differential diagnoses and diagnostic strategies in patients with chronic symptoms]

Abdominal pain is a very common complaint in a primary care consultation. The causes of abdominal pain are extremely diverse and range from conditions that require urgent surgical remedy to those without serious underlying pathology where the problem either settles spontaneously, or becomes chronic without any abnormalities on laboratory or clinical workup. While tests are helpful in confirming diagnoses, clinical judgement based on a careful history and physical examination remains extremely important in choosing from the extremely wide differential diagnoses and in the management of the condition. In this article, we will deal with chronically recurrent intermittent abdominal pain. Our aim is especially to provide guidance on the possibility that abdominal pain is a symptom of chronic inflammatory bowel disease (IBD) or an identifiable functional condition and when the diagnosis of irritable bowel syndrome should be made.

[Functional abdominal pain]

Functional abdominal pain is an inhomogeneous group of disorders concerning aetiology and clinical presentation. Support for classification is provided by the ROME-Foundation with its criteria catalogue, ROME-III being the most recent one. However, basic approach consists of exclusion of somatic or psychiatric as well as psychosomatic disorders that are sharply defined and readily diagnosable. This article outlines a pragmatic gastroenterological approach by exemplary means of dyspepsia and irritable bowel syndrome. Dyspepsia includes a broad complex of mainly epigastric located symptoms, whereas irritable bowel syndrome is symptomatic with altered bowel habits and mid-abdominal pain in the majority. Gastreoenterologic therapy modalities are mainly based on empirical and symptomatic grounds, more than on precisely explaining pathophysioligic understanding.

The impact of antibiotic associated diarrhea on health related quality of life in hospitalized patients

Objective. To determine the impact of antibiotic associated diarrhea (AAD) on health related quality of life (HRQOL) in hospitalized patients compared to matched controls without diarrhea. ^ Methods. This is a hospital-based, matched case-control study using secondary data from a prospective cohort trial of patients receiving broad-spectrum antibiotics. One hundred and seventy-eight patients were recruited of whom 18 (10%) reported having antibiotic associated diarrhea. Two non-diarrhea controls were selected for each case with diarrhea giving a final sample of 18 cases and 36 controls. Responses from Short Form (SF) 36 questionnaire were aggregated into eight domains including physical functioning (PF), role-functioning physical (RP), bodily pain (BP), general health (GH), social functioning (SF), vitality (VT), role-functioning emotional (RE), and mental health (MH). The eight domains were compared between cases and controls. A GI targeted HRQOL measure was administered to 13 patients with AAD. Responses from the disease-specific instrument were combined in eight subscale scores: dysphoria, interference with activity, body image, health worry, food avoidance, social reaction, sex, and relationships. ^ Results. The sample consisted of 41 females (75.9%) and 13 males (24.1%) aged 53.5 ± 14.4 years (range: 21-76 years). Twenty five patients (46%) were Caucasian, 15 (27%) were African American, 13(24%) were Hispanic and 1(2%) was Asian. In univariate analysis, no significant differences in quality of life outcomes were observed in each of the SF36 domains between the case patients and matched controls. There were trends for decreased scores on the role-functioning physical, bodily pain, general health, social functioning, mental health, and mental summary domains. In total, 7 of 8 domain scores were lower in patients with AAD and 5 of 8 domain scores were lower by more than 5 points (considered clinically significant). Controlling for age, patients with antibiotic associated diarrhea had significantly lower general health, vitality, and mental health scale scores (p<0.05 each). The disease-specific scores were significantly lower in patients with AAD than those in published norms for irritable bowel syndrome patients. ^ Conclusion. In this small sample, several areas of decreased QOL in patients with AAD compared to matched controls were noted. A larger sample size to validate these results is necessary.^

Special issue : The Human Intestinal Microbiota

Peer reviewed