Gut microbiota is essential for intestinal integrity and brain functions. Herein we aimed to investigate the effects of alteration of gut microbiome using broad-spectrum antibiotics on CD 1 male mice (germ-modified group (GM). Moreover, we co-administrated probiotics with or without antibiotics for four weeks and evaluated if probiotics could reverse these behavioral and intestinal effects. GM, co-administered antibiotics and probiotics, and probiotics-only groups were compared to control mice of the same sex, age, and weight that did not receive either drug (n=12 in all groups). Cultivation of aerobic and anaerobic bacteria was evaluated by fecal culture of all groups. We tested exploratory behavior, anxiety, memory, depression-like behavior, and hippocampal and frontal lobe BDNF protein level alterations in response to antibiotics and its downstream effect on the PI3K/Akt1/Bcl2 pathway. Intestinal integrity was evaluated using gene expression analysis of ZO-1, claudin, and occludin genes. Additionally, the inflammatory TLR4 and p-p38 MAPK pathways in the intestines were investigated. Twice-daily administration of oral antibiotics for four weeks significantly reduced total bacterial count and upregulated TLR4 and p-p38.GM mice showed a significant reduction in BDNF(P =0.04), impaired spatial memory, and long-term memory as evidenced by decreased T maze correct alternation trails and shortened retention time in the passive avoidance test in GM(P =0.01). Passive avoidance showed significantly increased latency after probiotics intake. Depressive-like behavior was more pronounced in GM mice as assessed by the tail suspension test (P =0.01). GM showed significant upregulation(p<0.001) of the TLR4 and p-p38 MAPK pathway. Co-administration of probiotics with antibiotics showed an increase in BDNF levels, and upregulation of the cell survival PI3K/Akt1/Bcl2 pathway, significantly higher relative abundance in the firmucutes members, a significant decrease in the Firmicutes/Bacteroidetes ratio and downregulation of TLR4 and p-p38 MAPK. The tight junction proteins ZO-1, claudin and occludin were downregulated by antibiotic administration for four weeks and restored by probiotics. Collectively, the data suggest that long-term use of antibiotics appears to disrupt the intestinal epithelial barrier and alter neurobehavioral qualities specifically, long-term memory and exploratory drive, possibly through the reduction of BDNF, and probiotics partially reverse these effects. Our study emphasizes the effect of prolonged intake of antibiotics on production of dysbiosis as well as the impact of the antibiotic induced intestinal inflammation on neurobehavioral aspects in mice as the memory and anxiety-like behavior. We also reveal that co-administration of probiotics can reverse these changes.

01 Sep 2024·Psychiatry Research

Antibiotic exposure and depression incidence: A cohort study of the Korean population

Article

Author: Chang, Jooyoung ; Jeong, Seogsong ; Ahn, Joseph C ; Park, Sang Min ; Kim, Jihoon Andrew ; Lee, Jaewon ; Son, Joung Sik ; Park, Sun Jae ; Choi, Seulggie ; Lee, Gyeongsil ; Park, Young Jun

Recent research highlights the crucial role of the gut-brain axis in understanding depression etiologies. While burgeoning studies suggest an association between disruptions in gut microbiota and the development of depression, limited longitudinal studies have investigated this link. To address this gap, we conducted a retrospective cohort study using National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data in South Korea, involving 199,144 individuals aged 40-79. We examined the impact of cumulative antibiotic exposure (2004-2008) on subsequent depression incidence (2009-2013) by conducting Cox proportional hazards regressions. Our findings show an increasing depression risk with extended antibiotic exposure after adjusting for comorbidities and behavioral covariates. A broader antibiotic spectrum was associated with a higher depression risk. These trends persisted after adjusting for the original antibiotic indications. In conclusion, our study highlights the duration-dependent association between antibiotic exposure and increased depression risk, offering insights into depression etiologies and relevant novel therapeutic tools, and advocating for heightened antibiotic stewardship considering their impact on mental health.

01 May 2024·BMJ Open

Childbirth Acquired Perineal Trauma study (CHAPTER): a UK prospective cohort study protocol

Article

Author: Tohill, Susan ; MacArthur, Christine ; Hodgetts Morton, Victoria ; Hughes, Terry ; Magill, Laura ; Perry, Rita ; Man, Rebecca ; Morris, R Katie

IntroductionChildbirth-related perineal trauma (CRPT) is the most common complication of childbirth affecting 80% of women overall after vaginal birth. There remains a lack of comprehensive evidence relating to the prevalence of subsequent health problems. Current evidence is related to short-term outcomes, for example, pain, but there is less known about longer-term outcomes such as infection, wound dehiscence, pelvic floor function and psychological outcomes. This is a protocol for a cohort study assessing outcomes of women after CRPT.Methods and analysisA multicentre, prospective UK cohort study aiming to include 1000 women. All women who have sustained CRPT will be eligible for inclusion and will be followed-up for 12 months after childbirth. The primary outcome will be perineal infection at 6 weeks post-birth. Secondary outcomes will include antibiotic use for perineal infection, wound breakdown, use of analgesia, the requirement for admission or surgical intervention, urinary and faecal incontinence, anxiety and depressive symptoms, sexual function and impact on daily activities. Outcomes will be measured at 6 weeks, 6 months and 12 months post partum, with some outcomes being measured at all time points and others at selected most appropriate time points only. Outcome data will be obtained from a review of clinical notes and from patient questionnaires. Simple descriptive statistics will be used to summarise characteristics and outcomes, with categorical variables expressed as percentages and continuous variables as mean averages, alongside the corresponding standard deviatons.Ethics and disseminationEthical approval has been granted by the Research Ethics Council with reference 23/WA/0169. Data collected from the Childbirth Acquired Perineal Trauma (CHAPTER) cohort study will highlight the prevalence and type of complications after CRPT and which women are more at risk. After the conclusion of this study, findings will be used to work with governmental organisations and Royal Colleges to target resources and ultimately improve care.

100 Deals associated with MRSA Antibiotics(Inimmune)

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Indication	Highest Phase	Country/Location	Organization	Date
MRSA - Methicillin resistant Staphylococcus aureus infection	Preclinical	US	Inimmune Corp.Startup	29 Oct 2024

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