Variations of rest-activity rhythm and sleep-wake in schizophrenic patients versus healthy subjects: An actigraphic comparative study

The objective of the present study was to compare the pattern of motor activity in unmedicated schizophrenia patients and healthy subjects, and to examine whether the pattern was affected by treatment with typical and atypical antipsychotics. Twenty unmedicated schizophrenic patients wore a wrist actigraph for five days. The actigraph recorded activity levels in one-minute epochs. Patients' pattern of activity was compared with that of healthy subjects. Patients were randomly assigned to treatment with low-dose haloperidol or risperidone. The impact of treatment on the pattern of activity was examined. Compared to controls, untreated patients showed a diminished mean activity count during morning, early and late night periods. Treatment with haloperidol or risperidone at effective doses showed a significant effect on activity level, being more prominent with haloperidol. The results suggest that unmedicated schizophrenic patients exhibit abnormally low levels of motor activity as measured with an objective activity meter. This persists after antipsychotic treatment even though symptoms improve. Future studies should clarify whether motor disturbances are a primary effect of the illness, or related to the illness-related lifestyle.     

Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia and bipolar disorder

Recent data from several reports indicate that free radicals are involved in aetiopathogenesis of many human pathologies including neuropsychiatric disorders such as schizophrenia, bipolar disorder etc. In the present study, we aimed at determining and evaluating levels of malondialdehyde (MDA), a product of lipid peroxidation, and antioxidant enzyme superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity levels in patients diagnosed with schizophrenia (n = 25) and bipolar disorder (n = 23). The control group was composed of 20 healthy subjects. There was a significant increase in MDA levels of patients with schizophrenia and bipolar disorder compared with controls. SOD and GSH-Px activity levels were significantly higher in the schizophrenic group compared with controls. SOD activity levels in bipolar the group were significantly higher than controls whereas there were no significant changes in GSH-Px activity levels in the bipolar group and controls. Significant differences between lipid peroxidation product and antioxidant enzyme (SOD and GSH-Px) activity levels in schizophrenic and bipolar disorder patients compared with controls leads us to believe that these differences are related to the heterogenities in aetiologies of these disorders.     

Thyroid activity in patients with major depression

Hypothalamus-pituitary-thyroid (HPT) axis dysfunction has been associated with pathophysiology of major depression. The aim of the study was to determine serum levels of total 3,5,3'-triiodothyronine (T3), total thyroxine (T4) and thyroid-stimulating-hormone (TSH) in patients with major depression and healthy controls. The study included 53 medication-free patients with depression and 49 healthy controls. Exclusion criteria for patients was: other axis-I and axis-II diagnoses, intensive psychotherapy or electroconvulsive therapy, prior clinical and/or laboratory evidence of hypo- or hyperthyroidism, alcohol or nicotine dependence, pregnancy, hormone supplement therapy, somatic illnesses (diabetes, renal or hepatic disorders), infections or autoimmune diseases, recent surgical treatment or significantly changed body weight. For controls: the presence of psychiatric disorders and/or thyroid dysfunctions. The diagnosis of major depression was made using structured clinical interview based on DSM-IV criteria. The results showed significantly lower T3 and TSH levels in patients compared to controls. There was no significant difference in T4 values between patients with depression and control subjects. The results showing altered levels of thyroid hormones in depression indicate that further research on thyroid hormone activity can contribute to the better understanding of the biological basis of depression. Based on the high frequency of the subtle neuroendocrine disorders coexisting with depression, the association of thyroid abnormalities and depression should not be underestimated. Future research should identify different behavioral endophenotypes characteristic for depression, which would greatly facilitate delineating the biological phenomena associated with this psychiatric illness.     

The difference between in bed and out of bed activity as a behavioral marker of cancer patients: A comparative actigraphic study

The current study was conducted to provide normative data on actigraphic dichotomy index (I?<?O) (the percentage of in bed activity counts that are less than the median of out of bed counts) in healthy population and to assess whether the I?<?O could be an effective index in discriminating the circadian motor activity of cancer patients from healthy controls. In this retrospective study, we recovered 408 actigraphic records from two databases: healthy controls (n?=?182; 79 males; mean age 38.7?±?12.6) and patients with metastatic colorectal cancer (n?=?226; 149 males; mean age 58.4?±?11.4). Beside the usual actigraphic sleep parameters (time in bed, sleep onset latency, total sleep time, wake after sleep onset, sleep efficiency, number of awakenings, and mean motor activity), we also computed the dichotomy index and number of actigraphic wake parameters, namely, diurnal motor activity, diurnal total sleep time, number of sleep episodes, and the mean duration of the longest diurnal sleep episode. Using the Youden index, we calculated the cut off value that performed the best for I?<?O and actigraphic wake parameters. Finally, we created Receiver Operator Characteristic curves to test the efficacy of each actigraphic parameter to discriminate cancer patient from healthy controls. Mean I?<?O was 99.5% (SD, 0.48%) in the healthy group, as compared to 96.6% (SD, 3.6%) in the cancer group (p?<?0.0001). Important age-related effects appeared unlikely after performing both the main analysis with age as a covariate, and a subset analysis in 104 subjects matched for age and sex. In the main analysis, all actigraphic parameters, except total sleep time, significantly differentiated the two groups of participants. However, the I?<?O was the one that clearly performed best. Here, we provide the first large dataset on I?<?O in healthy subjects, we confirm the relevance of this circadian index for discriminating advanced stage colorectal cancer patients from healthy subjects, and we lay the grounds for further investigations of this circadian index in patients with other chronic diseases.     

Lifetime prevalence of mood and anxiety disorders in twin pairs discordant for schizophrenia.

There have been long questions about the relationship of schizophrenia to other mental disorders. Lifetime DSM-III-R diagnoses of mood and anxiety disorders in twins with clinically diagnosed schizophrenia (n = 24) and their non-affected co-twins (n = 24) were compared with twins from pairs without schizophrenia (n = 3327) using a sample from the Vietnam Era Twin Registry. Schizophrenic probands had significantly elevated rates of all included disorders (bipolar disorder, major depression, dysthymia, generalized anxiety disorder, panic disorder, and PTSD) compared with controls (P<0.01). The odd ratios comparing co-twins of schizophrenic probands with controls was greater than three for every disorder, but did not attain statistical significance. A similar pattern was observed when analyses were restricted to only monozygotic twins (n = 12). Consistent with other studies, schizophrenics appeared to have higher rates of a range of mental disorders. Our results suggest that schizophrenia per se represents a risk factor for other psychiatric disorders, but the absence of significantly elevated risk among non-schizophrenic co-twins suggested that family environmental and/or genetic factors that contribute to risk of schizophrenia do not increase the risk of mood and anxiety disorders to the same extent that the risk of these other disorders is increased by the presence of schizophrenia.     

Neural chaos and schizophrenia

Recent data indicate that random-like processes are related to the defects in the organization of semantic memory in schizophrenia which is more disorganized and less definable than those of controls with more semantic links and more bizarre and atypical associations. These aspects of schizophrenic cognition are similar to characteristics of chaotic nonlinear dynamical systems. In this context, the hypothesis tested in this study is that dynamic changes of electrodermal activity (EDA) as a measure of brain and autonomic activity may serve as a characteristic which can be used as an indicator of possible neural chaotic process in schizophrenia. In the present study, bilateral EDA in rest conditions were measured in 40 schizophrenic patients and 40 healthy subjects. Results of nonlinear and statistical analysis indicate left-side significant differences of positive largest Lyapunov exponents in schizophrenia patients compared to the control group. This might be interpreted that the neural activity during rest in schizophrenic patients is significantly more chaotic than in the control group. The relationship was confirmed by surrogate data testing. These data suggest that increased neural chaos in patients with schizophrenia may influence brain processes that can cause random-like disorganization of mental processes.     

The effect of maximal exercise on the activity of neutrophil granulocytes in highly trained athletes in a moderate training period

Leucocyte cell counts and the phagocytic and chemotactic activities of neutrophil granulocytes were investigated in highly endurance-trained long-distance runners (n = 10) and triathletes (n = 10) during a moderate training period and compared with untrained subjects (n = 10) before and up to 24 h after a graded exercise to exhaustion on a treadmill. After exercise a leucocytosis was noted with a significant increase in lymphocyte (P < or = 0.01) and neutrophil (P < or = 0.01) counts in all groups. In neutrophils the number of ingested inert latex beads was significantly increased (P < or = 0.01) from 0.21 (SD 0.09) to 0.45 (SD 0.22) in controls, from 0.20 (SD 0.12) to 0.56 (SD 0.16) in long-distance runners and from 0.25 (SD 0.08) to 1.03 (SD 0.42) particles per cell in triathletes 24 h after exercise, compared with resting values. The capability of neutrophils to produce microbicidal reactive oxygen species fell (P < or = 0.05) immediately after exercise in all subjects and then increased by 36 (SD 8)%, 31 (SD 6)% and 19 (SD 9)% in controls, runners and triathletes respectively up to 24 h after exercise (P < or = 0.05) compared with pre-start values. With respect to the absolute number of neutrophils, ingestion capacity, production of superoxide anions and chemotactic activity, no significant differences were found between athletes and control subjects at rest and after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vertical displacement of the centre of mass during walking in people with diabetes and diabetic neuropathy does not explain their higher metabolic cost of walking

People with diabetes display biomechanical gait alterations compared to controls and have a higher metabolic cost of walking (CoW), but it remains unknown whether differences in the vertical displacement of the body centre of mass (CoM) may play a role in this higher CoW. The aim of this study was to investigate vertical CoM displacement (and step length as a potential underpinning factor) as an explanatory factor in the previously observed increased CoW with diabetes. Thirty-one non-diabetic controls (Ctrl); 22 diabetic patients without peripheral neuropathy (DM) and 14 patients with moderate/severe Diabetic Peripheral Neuropathy (DPN), underwent gait analysis using a motion analysis system and force plates while walking at a range of matched speeds between 0.6 and 1.6 m/s. Vertical displacement of the CoM was measured over the gait cycle, and was not different in either diabetes patients with or without diabetic peripheral neuropathy compared to controls across the range of matched walking speeds examined (at 1 m/s: Ctrl: 5.59 (SD: 1.6), DM: 5.41 (1.63), DPN: 4.91 (1.66) cm; p > 0.05). The DPN group displayed significantly shorter steps (at 1 m/s: Ctrl: 69, DM: 67, DPN: 64 cm; p > 0.05) and higher cadence (at 1 m/s: Ctrl: 117 (SD1.12), DM: 119 (1.08), DPN: 122 (1.25) steps per minute; p > 0.05) across all walking speeds compared to controls. The vertical CoM displacement is therefore unlikely to be a factor in itself that contributes towards the higher CoW observed recently in people with diabetic neuropathy. The higher CoW in patients with diabetes may not be explained by the CoM displacement, but rather may be more related to shorter step lengths, increased cadence and the associated increased internal work and higher muscle forces developed by walking with more flexed joints.     

Associations of Physical Activity,Sports Participation and Active Commuting on Mathematic Performance and Inhibitory Control in Adolescents

Objectives

To examine objectively measured physical activity level, organized sports participation and active commuting to school in relation to mathematic performance and inhibitory control in adolescents.

Methods

The design was cross-sectional. A convenient sample of 869 sixth and seventh grade students (12–14 years) was invited to participate in the study. A total of 568 students fulfilled the inclusion criteria and comprised the final sample for this study. Mathematic performance was assessed by a customized test and inhibitory control was assessed by a modified Eriksen flanker task. Physical activity was assessed with GT3X and GT3X+ accelerometers presented in sex-specific quartiles of mean counts per minute and mean minutes per day in moderate-to-vigorous physical activity. Active commuting and sports participation was self-reported. Mixed model regression was applied. Total physical activity level was stratified by bicycling status in order to bypass measurement error subject to the accelerometer.

Results

Non-cyclists in the 2^nd quartile of counts per minute displayed a higher mathematic score, so did cyclists in the 2^nd and 3^rd quartile of moderate-to-vigorous physical activity relative to the least active quartile. Non-cyclists in the 3^rd quartile of counts per minute had an improved reaction time and cyclists in the 2^nd quartile of counts per minute and moderate-to-vigorous physical activity displayed an improved accuracy, whereas non-cyclists in the 2^nd quartile of counts per minute showed an inferior accuracy relative to the least active quartile. Bicycling to school and organized sports participation were positively associated with mathematic performance.

Conclusions

Sports participation and bicycling were positively associated with mathematic performance. Results regarding objectively measured physical activity were mixed. Although, no linear nor dose-response relationship was observed there was no indication of a higher activity level impairing the scholastic or cognitive performance.     

Hypercholesterolemia and LDL receptor mRNA expression: modulation by selenium supplementation

Selenium (Se) status has been associated with cardiovascular disorders. Present study was aimed to elucidate the protective role of Se supplementation on LDL receptor (LDL-R) activity as well as mRNA expression during experimental hypercholesterolemia in SD male rats. Animals were fed 0.2 and 1 ppm Se supplemented control diet as well as 2% cholesterol supplemented diet for 3 months. LDL-R activity was measured in-vivo by injecting radiolabeled LDL to rats and decrease in counts per minute with time was taken as a measure of LDL clearance and in turn LDL-R activity. LDL-R mRNA expression was studied by RT-PCR. LDL-R activity and mRNA expression decreased significantly on 2% cholesterol supplemented diet feeding. On 1 ppm Se supplementation LDL-R activity as well as mRNA expression increased significantly. Present results demonstrate that Se supplementation upto 1 ppm is responsible for up regulation of LDL-R activity as well as mRNA expression, during hypercholesterolemia. These findings highlight the therapeutic potential of Se supplementation in lipid metabolism.     

A controlled study of Tourette syndrome. V. Depression and mania.

To evaluate the role of depression and mania in Tourette syndrome (TS), we have examined 246 TS patients, 17 attention-deficit disorder (ADD) patients, 15 patients with ADD associated with TS, and 47 controls, using (1) the standardized National Institutes of Mental Health Diagnostic Interview Schedule questions for a life history of major depression and/or mania and (2) a modified Beck depression score for evaluation of depression at the time of the examination. The results were combined into depression, Beck, and mania scores. Among the controls, 2.1% had a depression score greater than 9, and none had a score greater than 10. Among the TS patients, 22.9% had a score greater than 9 and the scores ranged up to the maximum of 18 (P less than .0005). None of the pure ADD patients had a score greater than 6, whereas 20% of the ADD-secondary-to-TS (ADD 2(0) TS) patients had scores greater than or equal to 9. Among grade 3 TS patients, 46.6% had scores greater than or equal to 9. There were no differences in the frequency of depression in the TS patients with or without ADD. Comparable results were obtained for the Beck depression score, except that the percent with a score greater than or equal to 8 was higher for the TS patients with ADD (23.7%) than for those without ADD (9.3%). There was a good correlation between the depression score and the Beck score (r = .63), but no correlation between the ADD-with-hyperactivity (ADDH) score and either the depression score (r = .086) or the Beck score (r = .077). Among the controls, none had a mania score greater than or equal to 4, compared with 19.1% of the total TS patients (P = less than .0005), 11.8% of the ADD patients (P = .002), and 26.6% of the ADD 2(0) TS patients (P = .0005). Although some of the mania questions would be expected to be answered positively by ADDH patients, the correlation coefficient between the ADDH scores and the mania scores was only moderate (r = .29), whereas the correlation with the depression score was much higher (r = .63). There was minimal correlation between the number of tics and either the depression score (r = .267) or the Beck score (r = .193). We conclude that depression and manic-depressive symptoms are common in TS patients and are an integral part of the disorder rather than being secondary to motor or vocal tics.     

Electric convulsive therapy (ECT) increases plasma and red blood cell haloperidol neuroleptic activities

In nine schizophrenic patients (five males and four females) on haloperidol treatment, plasma and red blood cell (RBC) haloperidol neuroleptic activities were measured before and after ECT by radioreceptor assay. Five patients randomly selected from these patients also served as controls on another occasion and neuroleptic activities in plasma and RBC were examined before and after the premedication only. All patients given ECT showed a considerable increase in plasma and RBC haloperidol neuroleptic activities after ECT (% increase in plasma neuroleptic activity, 28–409%; mean + SD, 136 ± 155%, P<0.005, Wilcoxon test; % increase in RBC neuroleptic activity, 11–121%; mean + SD, 59 ± 40%, P<0.005). However, no significant increase was observed for either plasma or RBC haloperidol neuroleptic activity, when patients were examined after premedication only. It was suggested that ECT induced a transient redistribution of haloperidol. It remains to be studied whether this phenomenon is causally related to the previous observation that the combination therapy of ECT and neuroleptics is more effective in the treatment of schizophrenia than ECT alone.     

2D-DIGE proteome analysis on the platelet proteins of patients with major depression

Introduction

Platelet activation is related to the psychopathology of major depression. We attempted to search and identify protein biomarkers from the platelets of patients with major depression. High resolution two-dimensional Differential Gel Electrophoresis (2D-DIGE), the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), Western blot, and bioinformatic tools were applied to examine the platelet proteins of 10 patients with major depression and 10 healthy controls.

Results

The levels of 8 proteins were significantly different between the patients with major depression in the acute phase and healthy controls. The levels of protein disulfide-isomerase A3 (PDIA3) and F-actin-capping protein subunit beta (CAPZB) were higher in patients with major depression than in healthy controls. The levels of fibrinogen beta chain (FIBB), fibrinogen gamma chain (FIBG), retinoic acid receptor beta (RARB), glutathione peroxidase 1 (GPX1), SH3 domain-containing protein 19 (SH319), and T-complex protein 1 subunit beta (TCPB) were lower in patients with major depression than in healthy controls.

Conclusions

Platelet provided valuable information about the pathways and processes of inflammation/immunity, oxidative stress, and neurogenesis, related to major depression.     

Plasma Protein Biomarkers for Depression and Schizophrenia by Multi Analyte Profiling of Case-Control Collections

Despite significant research efforts aimed at understanding the neurobiological underpinnings of psychiatric disorders, the diagnosis and the evaluation of treatment of these disorders are still based solely on relatively subjective assessment of symptoms. Therefore, biological markers which could improve the current classification of psychiatry disorders, and in perspective stratify patients on a biological basis into more homogeneous clinically distinct subgroups, are highly needed. In order to identify novel candidate biological markers for major depression and schizophrenia, we have applied a focused proteomic approach using plasma samples from a large case-control collection. Patients were diagnosed according to DSM criteria using structured interviews and a number of additional clinical variables and demographic information were assessed. Plasma samples from 245 depressed patients, 229 schizophrenic patients and 254 controls were submitted to multi analyte profiling allowing the evaluation of up to 79 proteins, including a series of cytokines, chemokines and neurotrophins previously suggested to be involved in the pathophysiology of depression and schizophrenia. Univariate data analysis showed more significant p-values than would be expected by chance and highlighted several proteins belonging to pathways or mechanisms previously suspected to be involved in the pathophysiology of major depression or schizophrenia, such as insulin and MMP-9 for depression, and BDNF, EGF and a number of chemokines for schizophrenia. Multivariate analysis was carried out to improve the differentiation of cases from controls and identify the most informative panel of markers. The results illustrate the potential of plasma biomarker profiling for psychiatric disorders, when conducted in large collections. The study highlighted a set of analytes as candidate biomarker signatures for depression and schizophrenia, warranting further investigation in independent collections.     

Convergent and Divergent Functional Connectivity Patterns in Schizophrenia and Depression

Major depression and schizophrenia are two of the most serious psychiatric disorders and share similar behavioral symptoms. Whether these similar behavioral symptoms underlie any convergent psychiatric pathological mechanisms is not yet clear. To address this issue, this study sought to investigate the whole-brain resting-state functional magnetic resonance imaging (MRI) of major depression and schizophrenia by using multivariate pattern analysis. Thirty-two schizophrenic patients, 19 major depressive disorder patients and 38 healthy controls underwent resting-state functional MRI scanning. A support vector machine in conjunction with intrinsic discriminant analysis was used to solve the multi-classification problem, resulting in a correct classification rate of 80.9% via leave-one-out cross-validation. The depression and schizophrenia groups both showed altered functional connections associated with the medial prefrontal cortex, anterior cingulate cortex, thalamus, hippocampus, and cerebellum. However, the prefrontal cortex, amygdala, and temporal poles were found to be affected differently by major depression and schizophrenia. Our preliminary study suggests that altered connections within or across the default mode network and the cerebellum may account for the common behavioral symptoms between major depression and schizophrenia. In addition, connections associated with the prefrontal cortex and the affective network showed promise as biomarkers for discriminating between the two disorders.     

Neural network analysis of the pattern of functional connectivity between cerebral areas in schizophrenia

 Recent evidence suggests that the core abnormality of cerebral function in schizophrenia is a disruption of functional connectivity between diverse cerebral sites. Functional connectivity is defined as the correlation between neuronal activity at remote sites. It can be measured using functional imaging techniques such as positron emission tomography (PET). This paper reports an analysis using a neural network to discriminate between the patterns of functional connectivity in schizophrenic patients and healthy subjects. The data was derived from a PET study of regional cerebral blood flow during word generation in 6 healthy subjects and 16 schizophrenic patients with established illness, in whom the clinical diagnosis could be made with confidence. After training on data from two healthy subjects and seven schizophrenic patients, the neural network successfully assigned all members of a test set of four healthy subjects and nine schizophrenic patients to the correct diagnostic category. While this result should be interpreted with caution on account of the small sample size, it indicates that neural network analysis is potentially of value in the diagnosis of schizophrenia. Received: 2 August 1999 / Accepted in revised form: 30 June 2000     

Impact of intermittent hypoxia on long-term facilitation of minute ventilation and heart rate variability in men and women: do sex differences exist?

Following exposure to intermittent hypoxia, respiratory motor activity and sympathetic nervous system activity may persist above baseline levels for over an hour. The present investigation was designed to determine whether sustained increases in minute ventilation and sympathovagal (S/V) balance, in addition to sustained depression of parasympathetic nervous system activity (PNSA), were greater in men compared with women following exposure to intermittent hypoxia. Fifteen healthy men and women matched for age, race, and body mass index were exposed to eight 4-min episodes of hypoxia during sustained hypercapnia followed by a 15-min end-recovery period. The magnitude of the increase in minute ventilation during the end-recovery period, compared with baseline, was similar in men and women (men, 1.52 +/- 0.03; women, 1.57 +/- 0.02 fraction of baseline; P < 0.0001). In contrast, depression of PNSA and increases in S/V balance were evident during the end-recovery period, compared with baseline, in men (PNSA, 0.66 +/- 0.06 fraction of baseline, P < 0.0001; S/V balance, 2.8 +/- 0.7 fraction of baseline, P < 0.03) but not in women (PNSA, 1.27 +/- 0.19 fraction of baseline, P = 0.3; S/V balance, 1.8 +/- 0.6 fraction of baseline, P = 0.2). We conclude that a sustained increase in minute ventilation, which is indicative of long-term facilitation, is evident in both men and women following exposure to intermittent hypoxia and that this response is independent of sex. In contrast, sustained alterations in autonomic nervous system activity were evident in men but not in women.     

Polyamine Oxidase Activity in Sera of Depressed and Schizophrenic Patients after ECT Treatment

High level of polyamine oxidase activity is detected in sera of depressed as well as in schizophrenic patients. ECT treatment of depressed and schizophrenic patients reduced significantly the level of polyamine oxidase activity in their sera. After ECT treatment, clinically improved depressed and schizophrenic subjects were found to have sera polyamine oxidase activity not significantly differ from that of normal subjects. Possible biochemical mechanisms, which link polyamine oxidase activity, schizophrenia, depression and ECT effect are discussed here.     

Use of a continuous culture fermentation system to investigate the effect of GanedenBC30 (Bacillus coagulans GBI-30, 6086) supplementation on pathogen survival in the human gut microbiota

Single-stage continuous fermentation systems were employed to examine the effects of GanedenBC(30) supplementation on the human gastrointestinal microbiota in relation to pathogen challenge in vitro. Denaturing gradient gel electrophoresis analysis demonstrated that GanedenBC(30) supplementation modified the microbial profiles in the fermentation systems compared with controls, with profiles clustering according to treatment. Overall, GanedenBC(30) supplementation did not elicit major changes in bacterial population counts in vitro, although notably higher Bcoa191 counts were seen following probiotic supplementation (compared to the controls). Pathogen challenge did not elicit significant modification of the microbial counts in vitro, although notably higher Clit135 counts were seen in the control system post-Clostridium difficile challenge than in the corresponding GanedenBC(30)-supplemented systems. Sporulation appears to be associated with the anti-microbial activity of GanedenBC(30), suggesting that a bi-modal lifecycle of GanedenBC(30)in vivo may lead to anti-microbial activity in distal regions of the gastrointestinal tract.