Maternal Antibiotic Exposure and the Risk of Developing Antenatal Depressive Symptoms.

Background: Antenatal depression is common and has significant consequences. The literature suggests that antibiotic exposure may be associated with depression. Many individuals are exposed to antibiotics during pregnancy. Further investigation of the association between antenatal antibiotic use and the development of depression during pregnancy is needed. Methods: A national prospective observational cohort study of pregnant individuals was undertaken using an online survey, completed during the third trimester. Antenatal depressive symptoms (ADSs) were defined as having an Edinburgh Postnatal Depression Scale score of ≥13 and/or receiving a clinical diagnosis of depression. Results: One in six individuals (16.5%, n = 977) experienced ADSs during their pregnancy, of whom 37.9% received a depression diagnosis. There was no relationship between antibiotic use and the development of ADSs. Four factors were identified as significant independent predictors of ADSs: personal history of depression, severe nausea and vomiting causing an inability to eat, emotional abuse from an intimate partner within the prior 12 months, and not having a university degree. Conclusions: Antenatal antibiotic use was not associated with the development of ADSs. Given the high incidence of undiagnosed depression, new strategies and models of care that prioritise individuals with risk factors may be required to optimise antenatal care.

Investigating the association between the symptoms of women with Fibromyalgia, Digestive function, and markers of the microbiota of the Gastrointestinal Tract (The FIDGIT Study): study protocol.

BACKGROUND: Fibromyalgia a common idiopathic condition affecting around 1.4% of adults globally. Its signature symptom is chronic widespread pain, with a constellation of somatic and psychological symptoms. Fibromyalgia is associated with significant reductions in quality of life, yet to date there is no biochemical marker for its diagnosis. Previous studies have indicated a strong association with gastrointestinal dysfunction, and more recently, alterations to the gut microbiome. No studies have examined the inter-relationship between fibromyalgia, gastrointestinal dysfunction, and the microbiome. This prospective observational case-controlled study will gather data on gastrointestinal function, dietary intake, fermentation patterns of ingested carbohydrates, and symptoms commonly associated with fibromyalgia. These will be evaluated alongside human gene expression and metatranscriptomic analysis of the oral and faecal microbiome. METHODS: Adult women aged ≥18 years diagnosed with fibromyalgia and/or meeting ACR 2016 criteria, and healthy family or age-matched controls will be recruited from the community. From consenting participants, we will collect detailed survey information and samples of blood, urine, stool, saliva, and breath. DISCUSSION: This is the first prospective study examining interactions between digestive function, human gene expression, and the gut microbiome together with general, and fibromyalgia-specific, symptoms experienced by New Zealand women. This exploration will allow an in-depth understanding of clinically relevant factors that are associated with fibromyalgia and will guide further research and contribute to improved management of this poorly understood condition. TRIAL REGISTRATION: The study was approved by the New Zealand Health and Disability Committee (HDEC) (ref: 20/CEN/197) and registered with the Australia and New Zealand Clinical Trials Registry (ANZCTR), registration number ACTRN12620001337965. Written consent will be obtained after providing participants with detailed information about the procedures. Access to data will be restricted to the immediate research team, and all samples and survey data will be deidentified and coded before analysis.

Effects of a high-prebiotic diet versus probiotic supplements versus synbiotics on adult mental health: The "Gut Feelings" randomised controlled trial.

Background: Preliminary evidence supports the use of dietary interventions and gut microbiota-targeted interventions such as probiotic or prebiotic supplementation for improving mental health. We report on the first randomised controlled trial (RCT) to examine the effects of a high-prebiotic dietary intervention and probiotic supplements on mental health. Methods: "Gut Feelings" was an 8-week, 2 × 2 factorial RCT of 119 adults with moderate psychological distress and low prebiotic food intake. Treatment arms: (1) probiotic supplement and diet-as-usual (probiotic group); (2) high-prebiotic diet and placebo supplement (prebiotic diet group); (3) probiotic supplement and high-prebiotic diet (synbiotic group); and (4) placebo supplement and diet-as-usual (placebo group). The primary outcome was assessment of total mood disturbance (TMD; Profile of Mood States Short Form) from baseline to 8 weeks. Secondary outcomes included anxiety, depression, stress, sleep, and wellbeing measures. Results: A modified intention-to-treat analysis using linear mixed effects models revealed that the prebiotic diet reduced TMD relative to placebo at 8 weeks [Cohen's d = -0.60, 95% confidence interval (CI) = -1.18, -0.03; p = 0.039]. There was no evidence of symptom improvement from the probiotic (d = -0.19, 95% CI = -0.75, 0.38; p = 0.51) or synbiotic treatments (d = -0.03, 95% CI = -0.59, 0.53; p = 0.92). Improved anxiety, stress, and sleep were noted in response to the prebiotic diet while the probiotic tentatively improved wellbeing, relative to placebo. No benefit was found in response to the synbiotic intervention. All treatments were well tolerated with few adverse events. Conclusion: A high-prebiotic dietary intervention may improve mood, anxiety, stress, and sleep in adults with moderate psychological distress and low prebiotic intake. A synbiotic combination of high-prebiotic diet and probiotic supplement does not appear to have a beneficial effect on mental health outcomes, though further evidence is required. Results are limited by the relatively small sample size. Clinical trial registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372753, identifier ACTRN12617000795392.

Hydrogen-methane breath testing results influenced by oral hygiene.

The measurement of hydrogen-methane breath gases is widely used in gastroenterology to evaluate malabsorption syndromes and bacterial overgrowth. Laboratories offering breath testing provide variable guidance regarding oral hygiene practices prior to testing. Given that oral dysbiosis has the potential to cause changes in breath gases, it raises concerns that oral hygiene is not a standard inclusion in current breath testing guidelines. The aim of this study was to determine how a pre-test mouthwash may impact hydrogen-methane breath test results. Participants presenting for breath testing who had elevated baseline gases were given a chlorhexidine mouthwash. If a substantial reduction in expired hydrogen or methane occurred after the mouthwash, breath samples were collected before and after a mouthwash at all breath sample collection points for the duration of testing. Data were evaluated to determine how the mouthwash might influence test results and diagnostic status. In 388 consecutive hydrogen-methane breath tests, modifiable elevations occurred in 24.7%. Administration of a chlorhexidine mouthwash resulted in significantly (p ≤ 0.05) reduced breath hydrogen in 67% and/or methane gas in 93% of those consenting to inclusion. In some cases, this modified the diagnosis. Mean total gas concentrations pre- and post-mouthwash were 221.0 ppm and 152.1 ppm (p < 0.0001) for hydrogen, and 368.9 ppm and 249.8 ppm (p < 0.0001) for methane. Data suggest that a single mouthwash at baseline has a high probability of returning a false positive diagnosis. Variations in gas production due to oral hygiene practices has significant impacts on test interpretation and the subsequent diagnosis. The role of oral dysbiosis in causing gastrointestinal symptoms also demands exploration as it may be an underlying factor in the presenting condition that was the basis for the referral.

A systematic review of the association between fibromyalgia and functional gastrointestinal disorders.

BACKGROUND: Fibromyalgia and functional gastrointestinal disorders (FGID) including irritable bowel syndrome (IBS) are common conditions presenting in clinical settings and are more prevalent in women. While the relationship between IBS and fibromyalgia has been demonstrated, a review of the prevalence of the broader group of FGID in adults with fibromyalgia has not been undertaken. The aim of this review was to systematically review the published literature, identifying the comorbidity of FGID in people with fibromyalgia, and to discuss the clinical implications, limitations of current research and areas of interest for future research. METHODS: Medline, Embase, CINAHL and Web of Science were searched during June 2019. Results were screened for original research articles meeting established criteria for identification of FGID in adults diagnosed with fibromyalgia. RESULTS: A total of 14 studies involving 1340 adults with fibromyalgia, 363 healthy controls and 441 adults with other pathologies were included in this review. Only 1 of the 14 studies included surveyed the full range of FGID . Functional gut disorders were matched to Rome II criteria for reporting and comparison. In addition to increased abdominal pain and functional bloating or gas, IBS of mixed-pattern and constipation-types appear to be more prevalent than diarrhoea-predominant IBS in adults with fibromyalgia. CONCLUSION: This review confirms previous reports that IBS is common in people living with fibromyalgia and suggests that IBS-mixed and constipation types predominate. An association with a range of FGID other than IBS is suggested, but data are limited. Research exploring the association between fibromyalgia and functional gastrointestinal dysfunction beyond IBS are warranted.

Integrative physiology and traditional naturopathic practice: Results of an international observational study.

BACKGROUND: Naturopathy is one of seven distinct traditional medical systems acknowledged by the World Health Organization. Naturopathic principles and philosophies encourage a focus on multiple body systems during case-taking and the design of treatments. Little is known about whether such teaching translates into practice. This study aimed to characterise naturopathic practice as it relates to the identification of multiple physiological systems in the diagnosis and treatment of patients. METHODS: A cross sectional study was conducted in collaboration with the World Naturopathic Federation. A survey capturing clinical diagnostic and treatment considerations for up to 20 consecutive patients was administered to naturopaths in 14 countries. RESULTS: Naturopaths (n = 56) were mostly female (62.5%), aged between 36 and 45 years (37.5%), in practice for 5-10 years (44.6%), and consulting between 11 and 20 patients per week (35.7%). Participants completed the survey for 851 patient cases. Naturopaths reported a greater number of physiological systems relevant to clinical cases where the patients were working age (18-65 years) (IRR 1.3, p = .042), elderly (65 years and over) (IRR 1.4, p = .046), or considered by the naturopath to have a chronic health condition (IRR 1.2, p = .003). The digestive system was weakly associated with patients based on chronicity of the health complaint (V = .1149, p = .004), or having a musculoskeletal complaint (V = .1067, p = .002) autoimmune pathophysiology (V = .1681, p < .001), and considered relevant in respiratory (V = .1042, p = .002), endocrine (V = .1023, p = .003), female reproductive (V = .1009, p = .003), and integumentary (V = .1382, p < .001) systems. CONCLUSION: Naturopaths across the world adopt an integrative physiological approach to the diagnosis and treatment of chronic and complex health care complaints..

Consumer Reports of "Keto Flu" Associated With the Ketogenic Diet.

Background: The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that limits glucose and results in the production of ketones by the liver and their uptake as an alternative energy source by the brain. KD is an evidence-based treatment for intractable epilepsy. KD is also self-administered, with limited evidence of efficacy, for conditions including weight loss, cognitive and memory enhancement, type II diabetes, cancer, neurological and psychiatric disorders. A commonly discussed side effect of KD in media and online forums is "keto flu," a cluster of transient symptoms generally reported as occurring within the first few weeks of KD. This study aimed to characterize the pattern of symptoms, severity and time course of keto flu as related by users of online forums. Method: Online forums referring to "keto flu," "keto-induction," or "keto-adaptation" in the URL were identified in Google. Passages describing personal experiences of keto flu were categorized manually with reference to pattern of symptoms, severity, time course, and remedies proposed. Results: The search criteria identified 75 online forums, 43 met inclusion criteria and contained 448 posts from 300 unique users. Seventy-three made more than one post (mean 3.12, range 2-11). Descriptors of personal experience of keto flu, reported by 101 of 300 users, included 256 symptom descriptions involving 54 discrete symptoms. Commonest symptoms were "flu," headache, fatigue, nausea, dizziness, "brain fog," gastrointestinal discomfort, decreased energy, feeling faint and heartbeat alterations. Symptom reports peaked in the first and dwindled after 4 weeks. Resolution of keto flu symptoms was reported by eight users between days 3 and 30 (median 4.5, IQR 3-15). Severity of symptoms, reported by 60 users in 40 forums, was categorized as mild (N = 15), moderate (N = 23), or severe (N = 22). Eighteen remedies were proposed by 121 individual users in 225 posts. Conclusions: Typically, individual posts provided fragmentary descriptions related to the flow of forum conversations. A composite picture emerged across 101 posts describing personally experienced symptoms. User conversations were generally supportive, sharing remedies for keto flu reflecting assumptions of physiological effects of KD.

Determining the association between fibromyalgia, the gut microbiome and its biomarkers: A systematic review.

BACKGROUND: The association between fibromyalgia and irritable bowel syndrome is well-established. Alterations in the composition and diversity of the gut microbiome in irritable bowel syndrome have been reported, however, this association is poorly understood in fibromyalgia. Our aim was to summarise the research reporting on the gastrointestinal microbiome and its biomarkers in people with fibromyalgia. METHODS: A systematic review of published original research reporting on the gastrointestinal microbiota and its biomarkers in adults with a diagnosis of fibromyalgia was undertaken. RESULTS: From 4771 studies, 11 met our inclusion criteria and were separated into four main groups: papers reporting Helicobacter pylori; other gut bacterial markers; metabolomics and other biomarkers, which included intestinal permeability and small intestinal bacterial overgrowth. CONCLUSION: The results suggest there is a paucity of quality research in this area, with indications that the gut microbiota may play a role in fibromyalgia within the emerging field of the gut-musculoskeletal axis. Further investigations into the relationship between the gut microbiota, gut dysfunction and fibromyalgia are warranted.

Western herbal medicines in the treatment of irritable bowel syndrome: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of Western herbal medicines in the treatment of irritable bowel syndrome (IBS). DESIGN: A computer-based search of MEDLINE, EMBASE, CINAHL, AMED, GreenFILE, Health Source: Nursing/Academic Edition, and the Cochrane Library was conducted. A hand-search of the bibliographies of relevant papers and previous meta-analyses and reviews was also undertaken. Trials were included in the review if they were double-blind and placebo-controlled investigating the effects of Western herbal medicines on IBS-related symptoms or quality of life. There were no language restrictions. Eligibility assessment and data extraction were performed by two independent researchers. For herbal medicines where there was more than 1 trial of similar design, data were synthesised using relative risk of symptoms improving using the random effects model. RESULTS: Thirty-three trials were identified that met all eligibility criteria. Seventeen of these evaluated peppermint essential oil, fifteen other Western herbal medicines, and one trial evaluated peppermint oil in one arm and aniseed essential oil in the other arm. Eighteen different herbal preparations were evaluated in these trials. Data suggests that a number of Western herbal medicines may provide relief of IBS symptoms. Meta-analyses suggest that peppermint essential oil is both efficacious and well-tolerated in the short-term management of IBS. Aloe vera and asafoetida also demonstrated efficacy in reducing global IBS symptoms in meta-analyses. The herbal formulas STW 5, STW 5-II and Carmint, along with Ferula assa-foetida, Pimpenella anisum oil, the combination of Curcumin and Foeniculum vulgare oil, and the blend of Schinopsis lorentzii, Aesculus hippocastanum, and peppermint essential oil also demonstrated efficacy in rigorously-designed clinical trials. CONCLUSION: A number of Western herbal medicines show promise in the treatment of IBS. With the exception of peppermint essential oil, Aloe vera, and asafoetida, however, none of the positive trials have been replicated. This lack of replication limits the capacity to make definitive statements of efficacy for these herbal medicines.

Mania Associated With Herbal Medicines, Other Than Cannabis: A Systematic Review and Quality Assessment of Case Reports.

Background: DSM-5 introduced the diagnostic category of substance/medication-induced bipolar and related disorder. This systematic review examines published reports linking mania with the consumption of herbal medicines (HM), excluding cannabis. Putative pathophysiological mechanisms that may account for the reported HM being associated with mania are discussed. Methods: A systematic search of EMBASE, CINAHL, Health Source, PsychINFO, and PubMed. The quality of case reports meeting inclusion criteria was assessed using the modified Quality Assessment Scale by Agbabiaka. Results: Nineteen single and seven multiple-case reports met inclusion criteria. These yielded a study sample of 35 case reports, 28 of herbal medicine associated mania, 5 of hypomania, and two mixed states, in 17 females [age in years M(SD) = 43.1(13.2)] and 18 males [40.7(18.1)]. A total of 11 herbal medicines were implicated. Case reports by herbal medicine (number of reports) comprised: St John's wort (Hypericum perforatum) (14); Ginseng (Panax ginseng) (5); brindleberry (Garcinia cambogia) (4); ma-huang (Ephedra sinica) (3); "herbal slimming pills" (2); Herbalife products (2); Hydroxycut (1); horny goat weed (Epimedium grandiflorum) (1); "herbal body tonic" (1); celery root (Apium graveolans) (1), and a "herbal mixture" (1). All case reports were associated with use rather than withdrawal of herbal medicines. Only one case report was rated for probability of association using a standardized algorithm. Laboratory assays to confirm composition of the herbal preparation were reported in only one article describing two cases and indicating admixture of a likely causal pharmaceutical in the herbal preparation. Conclusions: Causal attributions are problematic given the limited number of reports, antidepressant co-prescribing in 7 cases, insufficient data regarding pattern and type of herbal medicine use, and lack of a reference frequency for spontaneous mania.The quality assessment scores across the 26 papers (35 case reports) were as follows: low quality (0), lower-medium quality (9), upper-medium quality (10) and high quality (7). Putative pathophysiological mechanisms were postulated for nine of the 11 herbal medicines and centered on HPA-axis activation and increased monoamine activity. Systematic study of the association between herbal medicines and the course of bipolar disorder may contribute to defining targets for pathophysiological research.

Herbal medicines, other than St. John's Wort, in the treatment of depression: a systematic review.

OBJECTIVE: To evaluate herbal medicines, other than St. John's wort, in the treatment of depression. DATA SOURCES/SEARCH METHODS: A computer-based search of Medline, Cinahl, AMED, ALT Health Watch, Psych Articles, Psych Info, Current Contents databases, Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews, was performed. Researchers were contacted, and bibliographies of relevant papers and previous meta-analysis were hand searched for additional references. REVIEW METHODS: Trials were included in the review if they were prospective human trials assessing herbal medicines, other than St. John's wort, in the treatment of mild-to-moderate depression and utilized validated instruments to assess participant eligibility and clinical endpoints. RESULTS: Nine trials were identified that met all eligibility requirements. Three studies investigated saffron stigma, two investigated saffron petal, and one compared saffron stigma to the petal. Individual trials investigating lavender, Echium, and Rhodiola were also located. DISCUSSION: Results of the trials are discussed. Saffron stigma was found to be significantly more effective than placebo and equally as efficacious as fluoxetine and imipramine. Saffron petal was significantly more effective than placebo and was found to be equally efficacious compared to fluoxetine and saffron stigma. Lavender was found to be less effective than imipramine, but the combination of lavender and imipramine was significantly more effective than imipramine alone. When compared to placebo, Echium was found to significantly decrease depression scores at week 4, but not week 6. Rhodiola was also found to significantly improve depressive symptoms when compared to placebo. CONCLUSION: A number of herbal medicines show promise in the management of mild-to-moderate depression.

Effects of two natural medicine formulations on irritable bowel syndrome symptoms: a pilot study.

OBJECTIVE: The study objective was to assess the effects and tolerability of two novel natural medicine formulations in improving bowel habit and abdominal symptoms in patients with irritable bowel syndrome (IBS). The DA-IBS formula was designed to treat diarrhea-predominant and alternating bowel habit IBS, and the C-IBS formula was designed to treat constipation-predominant IBS. DESIGN: This was a two arm, open-label, uncontrolled pilot study. SETTINGS/LOCATION: Subjects were recruited from the greater Lismore area (NSW, Australia) in 2001. SUBJECTS: The study included 31 patients who fulfilled the Rome II criteria for IBS. Twenty-one (21) patients were classified as suffering from diarrhea-predominant or alternating bowel habit IBS and 10 patients were classified with constipation-predominant IBS. INTERVENTIONS: The DA-IBS formula consisted of a mixture of dried, powdered bilberry fruit, slippery elm bark, agrimony aerial parts, and cinnamon quills. The C-IBS formula consisted of a mixture of dried powdered slippery elm bark, lactulose, oat bran, and licorice root. The aim of each formula was to normalize stool frequency and stool consistency. RESULTS: Ingestion of the DA-IBS formula was associated with a small, but significant increase in bowel movement frequency (p = 0.027). Subjects in the DA-IBS group also experienced reductions in straining (p = 0.004), abdominal pain (p = 0.006), bloating (p < 0.0001), flatulence (p = 0.0001), and global IBS symptoms (p = 0.002) during the treatment phase of the trial. Subjects in the C-IBS group experienced a 20% increase in bowel movement frequency (p = 0.016) and significant reductions in straining (p < 0.0001), abdominal pain (p = 0.032), bloating (p = 0.034), and global IBS symptom severity (p = 0.0005), as well as improvements in stool consistency (p < 0.0001). Both formulas were well-tolerated. CONCLUSIONS: The DA-IBS formula was not effective in improving bowel habit in individuals with diarrhea-predominant or alternating bowel habit IBS, although it did significantly improve a number of IBS symptoms. The C-IBS formula significantly improved both bowel habit and IBS symptoms in patients with constipation-predominant IBS. Further research is warranted on C-IBS, as a potentially useful therapeutic formula.

Essential oils in the treatment of intestinal dysbiosis: A preliminary in vitro study.

INTRODUCTION: Dysbiosis is associated with a number of gastrointestinal and systemic disorders. There is a need for selectively acting antimicrobial agents capable of inhibiting the growth of potentially pathogenic microorganisms, or those found to be out of balance, while not negatively impacting the bulk gastrointestinal tract microflora. OBJECTIVE: The purpose of this in vitro study is to examine the potential of a selection of essential oils as agents to treat dysbiosis. MATERIALS AND METHODS: Eight essential oils were examined using the agar dilution method, including Carum carvi, Citrus aurantium var. amara, Foeniculum vulgare dulce, Illicium verum, Lavandula angustifolia, Mentha arvensis, Mentha x piperita, and Trachyspermum copticum. Doubling dilutions of the essential oils were tested against 12 species of intestinal bacteria, which represent the major genera found in the human gastrointestinal tract (GIT). RESULTS: Carum carvi, Lavandula angustifolia, Trachyspermum copticum, and Citrus aurantium var. amara essential oils displayed the greatest degree of selectivity, inhibiting the growth of potential pathogens at concentrations that had no effect on the beneficial bacteria examined. CONCLUSION: The most promising essential oils for the treatment of intestinal dysbiosis are Carum carvi, Lavandula angustifolia, Trachyspermum copticum, and Citrus aurantium var. amara. The herbs from which these oils are derived have long been used in the treatment of gastrointestinal symptoms and the in vitro results of this study suggest that their ingestion will have little detrimental impact on beneficial members of the GIT microflora. More research is needed, however, to investigate tolerability and safety concerns, and verify the selective action of these agents.

Is Lactobacillus rhamnosus GG effective in preventing the onset of antibiotic-associated diarrhoea: a systematic review.

OBJECTIVE: To evaluate the efficacy of Lactobacillus rhamnosus GG in the prevention of antibiotic-associated diarrhoea. DATA SOURCES: A computer-based search of MEDLINE, CINAHL, AMED, the Cochrane Controlled Trials Register and the Cochrane Database of Systematic Reviews was conducted. A hand-search of the bibliographies of relevant papers and previous meta-analyses was undertaken. REVIEW METHODS: Trials were included in the review if they compared the effects of L. rhamnosus GG and placebo and listed diarrhoea as a primary end-point. Studies were excluded if they were not placebo-controlled or utilised other probiotic strains. RESULTS: Six trials were found that met all eligibility requirements. Significant statistical heterogeneity of the trials precluded meta-analysis. Four of the six trials found a significant reduction in the risk of antibiotic-associated diarrhoea with co-administration of Lactobacillus GG. One of the trials found a reduced number of days with antibiotic-induced diarrhoea with Lactobacillus GG administration, whilst the final trial found no benefit of Lactobacillus GG supplementation. CONCLUSION: Additional research is needed to further clarify the effectiveness of Lactobacillus GG in the prevention of antibiotic-associated diarrhoea.

The causes of intestinal dysbiosis: a review.

Alterations in the bowel flora and its activities are now believed to be contributing factors to many chronic and degenerative diseases. Irritable bowel syndrome, inflammatory bowel disease, rheumatoid arthritis, and ankylosing spondylitis have all been linked to alterations in the intestinal microflora. The intestinal dysbiosis hypothesis suggests a number of factors associated with modern Western living have a detrimental impact on the microflora of the gastrointestinal tract. Factors such as antibiotics, psychological and physical stress, and certain dietary components have been found to contribute to intestinal dysbiosis. If these causes can be eliminated or at least attenuated then treatments aimed at manipulating the microflora may be more successful