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Use of Antibiotics and Risk of Psychiatric Disorders in Newly Diagnosed Cancer Patients: A Population-Based Cohort Study in Sweden.
BACKGROUND: Antibiotic-induced dysbiosis is associated with an increased risk of depression and anxiety in the general population. A diagnosis of cancer is associated with an immediately and dramatically elevated risk of psychiatric disorders, but the potential influence of prediagnostic antibiotic-induced dysbiosis is unknown. METHODS: Based on a national cohort of cancer patients in Sweden, we included 309,419 patients who were diagnosed with a first primary malignancy between July 2006 and December 2013. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of first-onset psychosis, depression, anxiety, or stress-related disorders during the first year after cancer diagnosis for antibiotic use during the year before cancer diagnosis. RESULTS: Compared with no antibiotic use, use of antibiotics was associated with a higher rate of the aforementioned psychiatric disorders (HR, 1.23; 95% CI, 1.16-1.30) after adjustment for sociodemographic factors, comorbidity, potential indications for antibiotics, and cancer stage and type. The magnitude of the association was higher for broad-spectrum antibiotics (HR, 1.27; 95% CI, 1.18-1.37), higher doses (HR, 1.32; 95% CI, 1.22-1.44), more frequent use (HR, 1.33; 95% CI, 1.21-1.46), and recent use (HR, 1.26; 95% CI, 1.17-1.35). CONCLUSIONS: Use of antibiotics, especially of broad-spectrum type, of high dose and frequency, with recent use, was associated with an aggravated risk of psychiatric disorders, compared with no antibiotic use. IMPACT: A better understanding of the microbiota-gut-brain axis may open up a wide avenue for the prevention and treatment of psychiatric disorders in cancer patients.
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Chemosensory Impairments and Their Impact on Nutrition in Parkinson's Disease: A Narrative Literature Review.
Parkinson's disease (PD) is a neurological disorder characterized by heterogeneous symptomatology, in which the classical motor features of Parkinsonism are associated with clinically significant non-motor symptoms. Olfactory alteration, as a manifestation of PD's premotor or prodromal phase, is well known. These impairments can lead to malnutrition, decreased appetite, and depression, thereby worsening patients' quality of life. However, only a few studies clarify the mechanisms, characteristics, and clinical diagnostic and therapeutic implications of impaired taste perception. Moreover, unlike most motor features of PD, non-motor symptoms often have limited treatment options or responses. The purpose of this review is to collate and describe all relevant studies on taste and smell alterations in patients with PD and how these alterations could affect nutritional status. Our search aimed to identify English-language research articles and reviews published in peer-reviewed journals over the past two decades (2004-2024), while also including older foundational studies when relevant. Several studies show that hyposmia in PD worsens over time, potentially linked to structural changes in the brain's basal ganglia and piriform cortex. Severe hyposmia is also associated with a higher risk of dementia in PD patients and can negatively influence quality of life, affecting social interactions and nutrition. Regarding taste perception, recent studies have suggested that hypogeusia may occur even in the prodromal stage of PD, such as in patients with REM sleep disorder, although the exact mechanisms remain unclear. Additionally, research has explored the role of bitter taste receptors and their possible involvement in inflammation and α-synuclein misfolding, suggesting a link between taste dysfunction and immune system changes in PD. Attention was then focused on the gut microbiota's link to the central nervous system and its contribution to gustatory dysfunctions, as well as how the nasal microbiome influences PD progression by altering the olfactory system. Nowadays, the primary role of a correct diet in the overall treatment of PD patients is becoming increasingly important for practitioners. Diet should be included among the available aids to counteract some aspects of the pathology itself. For all these reasons, it is also crucial to determine whether these chemosensory impairments could serve as disease markers, helping to better understand the underlying mechanisms of the disease.
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Prospective study of an amino acid-based elemental diet in an eosinophilic gastritis and gastroenteritis nutrition trial.
BACKGROUND: Eosinophilic gastritis/gastroenteritis (EoG/EoGE) are rare disorders with pathologic gastric and/or small intestinal eosinophilia lacking an approved therapy. An allergic mechanism is postulated but underexplored mechanistically and therapeutically. OBJECTIVE: We evaluated the effectiveness of a food allergen-free diet (elemental formula) in controlling gastrointestinal eosinophilia in adult EoG/EoGE. METHODS: Adults aged 18 to 65 years with histologically active EoG/EoGE (≥30 eosinophils per high-power field) in the stomach and/or duodenum and gastrointestinal symptoms within the month preceding enrollment were prospectively enrolled onto a single-arm clinical trial to receive elemental formula for 6 consecutive weeks. The primary end point was percentage of participants with complete histologic remission (<30 eosinophils per high-power field in both stomach and duodenum). Exploratory outcomes were improvement in symptoms, endoscopy results, blood eosinophilia, quality of life, Physician Global Assessment score, and EoG-relevant gastric transcriptome and microbiome. RESULTS: Fifteen adults (47% male, average age 37.7 years, average symptom duration 8.8 years) completed the trial. Multi-gastrointestinal segment involvement affected 87%. All subjects had complete histologic remission in the stomach (P = .002) and duodenum (P = .001). Scores improved in overall PhGA (P = .002); EGREFS (P = .003); EGDP (P = .002); SODA pain intensity (P = .044), non-pain (P = .039), and satisfaction (P = .0024); and PROMIS depression (P = .0078) and fatigue (P = .04). Food reintroduction reversed these improvements. The intervention was well tolerated in 14 subjects, with 1 serious adverse event reported in 1 subject. CONCLUSION: An amino acid-based elemental diet improves histologic, endoscopic, symptomatic, quality-of-life, and molecular parameters of EoG/EoGE; these findings and disease recurrence with food trigger reintroduction support a dominant role for food allergens in disease pathogenesis. CLINICALTRIALS: gov Identifier: NCT03320369.
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Intestinal colonization of germ-free mice with indole-producing E. coli modulates the central and peripheral endocannabinoidome.
Colonization of germ-free (GF) mice with indole-producing E. coli exacerbates anxiety- and depression-like behaviors. Lack and subsequent reintroduction of gut microbiota in mice alter in opposing ways the brain and intestinal levels of the lipid mediators of the expanded endocannabinoid system, or endocannabinoidome (eCBome), which controls affective behaviors. By using LC/MS-MS-based targeted lipidomics and qPCR, we investigated the effect of GF mouse colonization with E. coli strains capable (wild-type, I+) or not (knock-out, I-) of producing indole, on the brain and intestinal eCBome. Compared to untreated GF mice, and unlike the I- strain, the I+ strain reduced the levels of 2-monoacylglycerols (2-MAGs), and 2-arachidonoylglycerol in particular, in the amygdala, and of 2-MAGs and NAEs in the hippocampus. Moreover, it elevated 2-MAGs in the ileum and reduced NAEs in the cecum. The mRNA expression of some eCBome receptors was also selectively altered by the I+ strain, including Gpr55 (upregulated in the amygdala), Gpr18 (downregulated in the ileum), Cnr2 (upregulated in the colon), and Gpr119 (downregulated in the cecum). LC/MS-MS-based targeted metabolomics detected the indole metabolite indoxyl-3-sulfate in the plasma and liver, but not brain, of I+-colonized mice. Our data pinpoint the eCBome as a potential mediator of the effects of indole.
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Probiotic, prebiotic, synbiotic and fermented food supplementation in psychiatric disorders: A systematic review of clinical trials.
The use of probiotics, prebiotics, synbiotics or fermented foods can modulate the gut-brain axis and constitute a potentially therapeutic intervention in psychiatric disorders. This systematic review aims to identify current evidence regarding these interventions in the treatment of patients with DSM/ICD psychiatric diagnoses. Forty-seven articles from 42 studies met the inclusion criteria. Risk of bias was assessed in all included studies. Major depression was the most studied disorder (n = 19 studies). Studies frequently focused on schizophrenia (n = 11) and bipolar disorder (n = 5) and there were limited studies in anorexia nervosa (n = 4), ADHD (n = 3), Tourette (n = 1), insomnia (n = 1), PTSD (n = 1) and generalized anxiety disorder (n = 1). Except in MDD, current evidence does not clarify the role of probiotics and prebiotics in the treatment of mental illness. Several studies point to an improvement in the immune and inflammatory profile (e.g. CRP, IL6), which may be a relevant mechanism of action of the therapeutic response identified in these studies. Future research should consider lifestyle and dietary habits of patients as possible confounders that may influence inter-individual treatment response.
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The Add-On Effect of Lactobacillus plantarum PS128 in Patients With Parkinson's Disease: A Pilot Study.
Background: Lactobacillus plantarum PS128 (PS128) is a specific probiotic, known as a psychobiotic, which has been demonstrated to alleviate motor deficits and inhibit neurodegenerative processes in Parkinson's disease (PD)-model mice. We hypothesize that it may also be beneficial to patients with PD based on the possible mechanism via the microbiome-gut-brain axis. Methods: This is an open-label, single-arm, baseline-controlled trial. The eligible participants were scheduled to take 60 billion colony-forming units of PS128 once per night for 12 weeks. Clinical assessments were conducted using the Unified Parkinson's Disease Rating Scale (UPDRS), modified Hoehn and Yahr scale, and change in patient "ON-OFF" diary recording as primary outcome measures. The non-motor symptoms questionnaire, Beck depression inventory-II, patient assessment of constipation symptom, 39-item Parkinson's Disease Questionnaire (PDQ-39), and Patient Global Impression of Change (PGI-C) were assessed as secondary outcome measures. Results: Twenty-five eligible patients (32% women) completed the study. The mean age was 61.84 ± 5.74 years (range, 52-72), mean disease duration was 10.12 ± 2.3 years (range, 5-14), and levodopa equivalent daily dosage was 1063.4 ± 209.5 mg/daily (range, 675-1,560). All patients remained on the same dosage of anti-parkinsonian and other drugs throughout the study. After 12 weeks of PS128 supplementation, the UPDRS motor scores improved significantly in both the OFF and ON states (p = 0.004 and p = 0.007, respectively). In addition, PS128 intervention significantly improved the duration of the ON period and OFF period as well as PDQ-39 values. However, no obvious effect of PS128 on non-motor symptoms of patients with PD was observed. Notably, the PGI-C scores improved in 17 patients (68%). PS128 intervention was also found to significantly reduce plasma myeloperoxidase and urine creatinine levels. Conclusion: The present study demonstrated that PS128 supplementation for 12 weeks with constant anti-parkinsonian medication improved the UPDRS motor score and quality of life of PD patients. We suggest that PS128 could serve as a therapeutic adjuvant for the treatment of PD. In the future, placebo-controlled studies are needed to further support the efficacy of PS128 supplementation. Clinical Trial Registration: https://clinicaltrials.gov/, identifier: NCT04389762.
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Effects of intravenous lipopolysaccharide administration on physiological and ruminal responses that modulate feed intake in beef cattle.
This experiment evaluated feed intake, physiological reactions, and ruminal parameters in beef cattle receiving or not receiving a lipopolysaccharide (LPS) challenge. Ten ruminally-cannulated Angus steers [590 ± 16 kg of body weight (BW)] were housed in individual pens on day -7, ranked by BW, and allocated to 1 of 2 treatments administered intravenously on day 0: 1) 0.5 μg/kg of BW of bacterial LPS (Escherichia coli 0111:B4) diluted in 5 mL of 0.9% sterile saline, or 2) 5 mL of 0.9% physiological saline (CON). Steers had free-choice access to wheat hay, water, and a commercial vitamin + mineral mix (days -7 to 7). Hay dry matter intake (DMI) was evaluated daily from days -5 to 7. Prior to treatment administration on day 0 (hour 0), polyester bags containing 4 g of ground dietary hay (DM basis) were immersed into the rumen of each steer, and incubated for 0, 4, 8, 12, 24, 36, 48, 60, and 72 h for dry matter (DM) and neutral detergent fiber (NDF) degradability evaluation. Steers were also intra-ruminally pulse-dosed with 5 g of Co-EDTA and with Cr-EDTA (0.1 g/kg of BW) prior to treatment administration. Rumen fluid samples were collected at 0, 2, 4, 6, 8, 12, 16, 24, 36, and 48 h, and blood samples were collected at -2, 0, 2, 4, 6, 8, 12, 18, 24, 36, 48, 60, 72, 96, 120, and 144 h relative treatment administration. Values obtained before treatment administration were used as covariates within each respective analysis. Steers receiving LPS had less (P ≤ 0.05) hay DMI on days 0 and 1, less (P < 0.01) rumen liquid volume and dilution rate, and less (P < 0.01) ruminal effective degradability of DM and NDF compared with CON. Steers receiving LPS had greater (P ≤ 0.05) plasma haptoglobin concentration from 18 to 144 h, greater (P ≤ 0.04) plasma cortisol concentration from 2 to 12 h, and less (P ≤ 0.04) total plasma Cr concentration from 2 to 18 h compared with CON. Steers receiving LPS had less (P ≤ 0.03) mean concentrations of acetate, butyrate, valerate, and total volatile fatty acids (VFA) in the rumen fluid compared with CON. Steers receiving LPS had less (P ≤ 0.05) mean total bacterial load in the ruminal fluid, and less mean prevalence of the phyla Spirochaetes and Fibrobacteres and the genera Treponema compared with CON. Results from this experiment suggest that LPS administration elicited host-microbiome endocrine interactions that impaired feed degradability and VFA production in the rumen, particularly a reduction in total bacterial load, which may have contributed to a 48-h decrease in hay DMI.
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The Role of the Oral Microbiota Related to Periodontal Diseases in Anxiety, Mood and Trauma- and Stress-Related Disorders.
The prevalence of anxiety, mood and trauma- and stress-related disorders are on the rise; however, efforts to develop new and effective treatment strategies have had limited success. To identify novel therapeutic targets, a comprehensive understanding of the disease etiology is needed, especially in the context of the holobiont, i.e., the superorganism consisting of a human and its microbiotas. Much emphasis has been placed on the role of the gut microbiota in the development, exacerbation, and persistence of psychiatric disorders; however, data for the oral microbiota are limited. The oral cavity houses the second most diverse microbial community in the body, with over 700 bacterial species that colonize the soft and hard tissues. Periodontal diseases encompass a group of infectious and inflammatory diseases that affect the periodontium. Among them, periodontitis is defined as a chronic, multi-bacterial infection that elicits low-grade systemic inflammation via the release of pro-inflammatory cytokines, as well as local invasion and long-distance translocation of periodontal pathogens. Periodontitis can also induce or exacerbate other chronic systemic inflammatory diseases such as atherosclerosis and diabetes and can lead to adverse pregnancy outcomes. Recently, periodontal pathogens have been implicated in the etiology and pathophysiology of neuropsychiatric disorders (such as depression and schizophrenia), especially as dysregulation of the immune system also plays an integral role in the etiology and pathophysiology of these disorders. This review will discuss the role of the oral microbiota associated with periodontal diseases in anxiety, mood and trauma- and stress-related disorders. Epidemiological data of periodontal diseases in individuals with these disorders will be presented, followed by a discussion of the microbiological and immunological links between the oral microbiota and the central nervous system. Pre-clinical and clinical findings on the oral microbiota related to periodontal diseases in anxiety, mood and trauma- and stress-related phenotypes will be reviewed, followed by a discussion on the bi-directionality of the oral-brain axis. Lastly, we will focus on the oral microbiota associated with periodontal diseases as a target for future therapeutic interventions to alleviate symptoms of these debilitating psychiatric disorders.
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Functional brain rewiring and altered cortical stability in ulcerative colitis.
Despite recent advances, there is still a major need to better understand the interactions between brain function and chronic gut inflammation and its clinical implications. Alterations in executive function have previously been identified in several chronic inflammatory conditions, including inflammatory bowel diseases. Inflammation-associated brain alterations can be captured by connectome analysis. Here, we used the resting-state fMRI data from 222 participants comprising three groups (ulcerative colitis (UC), irritable bowel syndrome (IBS), and healthy controls (HC), N = 74 each) to investigate the alterations in functional brain wiring and cortical stability in UC compared to the two control groups and identify possible correlations of these alterations with clinical parameters. Globally, UC participants showed increased functional connectivity and decreased modularity compared to IBS and HC groups. Regionally, UC showed decreased eigenvector centrality in the executive control network (UC < IBS < HC) and increased eigenvector centrality in the visual network (UC > IBS > HC). UC also showed increased connectivity in dorsal attention, somatomotor network, and visual networks, and these enhanced subnetwork connectivities were able to distinguish UC participants from HCs and IBS with high accuracy. Dynamic functional connectome analysis revealed that UC showed enhanced cortical stability in the medial prefrontal cortex (mPFC), which correlated with severe depression and anxiety-related measures. None of the observed brain changes were correlated with disease duration. Together, these findings are consistent with compromised functioning of networks involved in executive function and sensory integration in UC.
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Assessing the effect of anthocyanins through diet and supplementation on cognitive function in older adults at risk for dementia: protocol for a randomised controlled trial.
INTRODUCTION: Promising evidence is emerging for the procognitive, anti-inflammatory and neuroprotective properties of dietary flavonoids, particularly anthocyanins that provide red, purple and blue plant pigments. METHODS AND ANALYSIS: The 'Food for Thought' study is a multicentre, 6-month randomised, parallel 3-arm clinical trial. Its primary aim is to investigate whether anthocyanin consumption, either through diet or supplementation, can prevent memory loss progression and improve inflammatory and cardiovascular health in older adults at risk for dementia. Eligible participants will include those aged 60-85 years with a diagnosis of amnestic mild cognitive impairment or with a self-referral of memory concerns and scoring ≤13 on the Memory Index Score within the Telephone Montreal Cognitive Assessment screening test. Participants will be randomised to one of three arms: High anthocyanin ('purple foods') diet (aiming for a target of 250 mg anthocyanins/day); freeze-dried product derived from blackcurrants (250 mg anthocyanins/day); or control (coloured maltose powder). The primary outcome is auditory anterograde memory functioning assessed by the Buschke and Grober Free and Cued Selective Reminding Test-Immediate Recall. Secondary outcomes are additional cognitive functions including processing speed, working memory, aspects of executive functioning (attentional shifting and word generativity) and premorbid estimate as well as subjective memory problems and self-reported depression symptoms. Additional secondary outcomes are blood pressure, inflammatory biomarkers, brain-derived neurotrophic factor, fatty acid profile, apolipoprotein E and polyphenol metabolites, gut microbiota composition and function and vascular and microvascular endothelial function tests. Repeated measures analysis of variance and/or mixed linear modelling will evaluate changes over time, with the inclusion of covariates. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Greater Western Human Research Ethics Committee (2021/ETH12083). A Consumer Advisory Group was established to guide and review the protocol and dissemination strategy. The results of this trial are intended to be published in a peer-reviewed journal. TRIAL SPONSOR: National Health and Medical Research Centre Dementia Collaborative Research Centre.Start date of clinical trial: 02 September 2022.Expected end date: 11 October 2024. TRIAL REGISTRATION NUMBER: ACTRN12622000065796.