Depletion of acetate-producing bacteria from the gut microbiota facilitates cognitive impairment through the gut-brain neural mechanism in diabetic mice

Abstract Background Modification of the gut microbiota has been reported to reduce the incidence of type 1 diabetes mellitus (T1D). We hypothesized that the gut microbiota shifts might also have an effect on cognitive functions in T1D. Herein we used a non-absorbable antibiotic vancomycin to modify the gut microbiota in streptozotocin (STZ)-induced T1D mice and studied the impact of microbial changes on cognitive performances in T1D mice and its potential gut-brain neural mechanism. Results We found that vancomycin exposure disrupted the gut microbiome, altered host metabolic phenotypes, and facilitated cognitive impairment in T1D mice. Long-term acetate deficiency due to depletion of acetate-producing bacteria resulted in the reduction of synaptophysin (SYP) in the hippocampus as well as learning and memory impairments. Exogenous acetate supplement or fecal microbiota transplant recovered hippocampal SYP level in vancomycin-treated T1D mice, and this effect was attenuated by vagal inhibition or vagotomy. Conclusions Our results demonstrate the protective role of microbiota metabolite acetate in cognitive functions and suggest long-term acetate deficiency as a risk factor of cognitive decline.

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Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: a prospective randomized pilot study

Microbial Cell Factories ◽

10.1186/s12934-021-01513-6 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Haiming Fang ◽

Lian Fu ◽

Xuejun Li ◽

Chunxia Lu ◽

Yuan Su ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

Fecal Microbiota ◽

Control Group ◽

Microbiota Composition ◽

Fecal Microbiota Transplant ◽

Significant Difference ◽

The Mean

Abstract Background To assess the long-term safety and efficacy of monotherapy with a single fresh fecal microbiota transplant (FMT) for recurrent ulcerative colitis (UC). Results Twenty-six eligible patients were enrolled, and 6 patients were excluded. Ultimately, 20 patients were randomized to the FMT group (n = 10) and the control group (n = 10); 80% were females (F/M = 16/4), the mean age was 48 ± 14 years, and the mean duration was 6.4 ± 8.2 years. The mean length of post-FMT follow-up was 19.1 ± 10.1 months (6–38). No statistically significant differences in baseline demographic or clinical characteristics were found between the groups. Ninety percent of patients in the FMT group and 50% of patients in the control group met the primary endpoint at week 8. The Mayo score was significantly decreased compared with that of the control group (n = 10) when reassessed at week 4 (P = 0.001) and week 8 (P = 0.019) after FMT; there was no significant difference 6 months after treatment. The median remission time was 24 months (95% CI 68.26–131.7%) in both the FMT (range 6–38 months) and control groups (range 7–35 months), with no significant difference (P = 0.895). Participants tolerated FMT treatment, and no adverse events occurred during long-term follow-up, with one treatment-related significant adverse event (EBV infection) occurring within 2 weeks after FMT. Stool microbiota composition analysis indicated improved gut microbiota diversity after FMT, with expansion of stool-donor taxa. Bacteroidetes, Firmicutes and Proteobacteria were the dominant bacterial phyla of the gut microbiota in active UC patients. The relative abundance of Bacteroidetes decreased and that of Proteobacteria increased significantly in active UC patients compared with donors, while Firmicutes showed no significant changes. A single fresh FMT could effectively reconstruct the gut microbiota composition in patients with active UC and maintain stability, with increased Bacteroidetes and decreased Proteobacteria abundance. FMT significantly reduced the relative abundance of Escherichia and increased the relative abundance of Prevotella at the genus level. Pyruvate metabolism, glyoxylate and dicarboxylate metabolism, and pantothenate and CoA biosynthesis showed significant differences after transplantation. Conclusions Monotherapy with a single fresh FMT is an effective and safe strategy to induce long-term remission without drugs in patients with active UC and may be an alternative induction therapy for recurrent UC or even primary UC.

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Modulation of Gut Microbiota and Oxidative Status by β-Carotene in Late Pregnant Sows

Frontiers in Nutrition ◽

10.3389/fnut.2020.612875 ◽

2020 ◽

Vol 7 ◽

Author(s):

Xupeng Yuan ◽

Jiahao Yan ◽

Ruizhi Hu ◽

Yanli Li ◽

Ying Wang ◽

...

Keyword(s):

Gut Microbiota ◽

Dietary Supplementation ◽

Basal Diet ◽

Fecal Microbiota ◽

Control Group ◽

Metabolic Activities ◽

The Impact ◽

Positive Effect ◽

Β Carotene

Recent evidences suggest that gut microbiota plays an important role in regulating physiological and metabolic activities of pregnant sows, and β-carotene has a potentially positive effect on reproduction, but the impact of β-carotene on gut microbiota in pregnant sows remains unknown. This study aimed to explore the effect and mechanisms of β-carotene on the reproductive performance of sows from the aspect of gut microbiota. A total of 48 hybrid pregnant sows (Landrace × Yorkshire) with similar parity were randomly allocated into three groups (n = 16) and fed with a basal diet or a diet containing 30 or 90 mg/kg of β-carotene from day 90 of gestation until parturition. Dietary supplementation of 30 or 90 mg/kg β-carotene increased the number of live birth to 11.82 ± 1.54 and 12.29 ± 2.09, respectively, while the control group was 11.00 ± 1.41 (P = 0.201). Moreover, β-carotene increased significantly the serum nitric oxide (NO) level and glutathione peroxidase (GSH-Px) activity (P < 0.05). Characterization of fecal microbiota revealed that 90 mg/kg β-carotene increased the diversity of the gut flora (P < 0.05). In particular, β-carotene decreased the relative abundance of Firmicutes including Lachnospiraceae AC2044 group, Lachnospiraceae NK4B4 group and Ruminococcaceae UCG-008, but enriched Proteobacteria including Bilophila and Sutterella, and Actinobacteria including Corynebacterium and Corynebacterium 1 which are related to NO synthesis. These data demonstrated that dietary supplementation of β-carotene may increase antioxidant enzyme activity and NO, an important vasodilator to promote the neonatal blood circulation, through regulating gut microbiota in sows.

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Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis

Biomedicines ◽

10.3390/biomedicines9020145 ◽

2021 ◽

Vol 9 (2) ◽

pp. 145

Author(s):

Julio Plaza-Díaz ◽

Patricio Solis-Urra ◽

Jerónimo Aragón-Vela ◽

Fernando Rodríguez-Rodríguez ◽

Jorge Olivares-Arancibia ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Liver Steatosis ◽

Intestinal Barrier ◽

Fecal Microbiota ◽

Current Treatment ◽

Immune Defense ◽

Alcoholic Fatty Liver ◽

The Impact

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).

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The Association between Physical Activity and Selected Parameters of Psychological Status and Dementia in Older Women

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18147549 ◽

2021 ◽

Vol 18 (14) ◽

pp. 7549

Author(s):

Angelika Cisek-Woźniak ◽

Kinga Mruczyk ◽

Rafał W. Wójciak

Keyword(s):

Mental Health ◽

Physical Activity ◽

Cognitive Impairment ◽

Cognitive Functioning ◽

Cognitive Functions ◽

Protective Factor ◽

The Elderly ◽

Regular Physical Activity ◽

Psychological Status ◽

The Impact

Physical activity has an unquestionable impact on broadly understood human health. One interesting issue related to this is the importance of movement on mental health and cognitive functioning. Research shows that regular physical activity improves the cognitive functioning of adults and people with mental disorders. Regular physical activity can be an important and powerful protective factor in cognitive impairment and dementia in the elderly, and exercise is an important non-pharmacological treatment for mild cognitive impairment or neurodegenerative diseases. This study aims to present the impact of physical activity on selected cognitive functions in physically active women over 60 years of age. The research was carried out in a group of 110 generally healthy women from the area of western Poland over 60 years of age, who were divided into four groups based on the intensity of their physical activity. A pedometer (sport watch) and a physical activity diary were used to measure physical activity. Body Mass Index was assessed. Selected cognitive functions were assessed using the MMSE test, motor and psychomotor skills were measured, and Luria’s auditory memory test and recall test, a clock drawing test, and a GDS test were performed. There were statistically significant relationships between the level of physical activity and the effectiveness of cognitive processes. These results show that about 5000 steps a day is enough to see a positive effect on the mental health and cognitive functioning of this group of the elderly population. The women had an average BMI of 28.1 ± 4.7. BMI, indicating an overweight condition (over 30 kg/m2), was observed in 31% of women. The results of this study lead the authors to conclude that physical activity positively influences cognitive function and can be recommended for all seniors who do not have other serious comorbidities that would prevent them from playing sports.

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The Role of The Gut Microbiome in Parkinson’s Disease

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/08919887211018268 ◽

2021 ◽

Vol 34 (4) ◽

pp. 253-262

Author(s):

Amy Gallop ◽

James Weagley ◽

Saif-ur-Rahman Paracha ◽

George Grossberg

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Gut Microbiota ◽

Symptom Relief ◽

Antibiotic Use ◽

Fecal Microbiota ◽

Fermented Food ◽

Fecal Microbiota Transplant ◽

Disease States ◽

Cord Blood Transplant

The gut microbiota is known to play a role in various disease states through inflammatory, immune and endocrinologic response. Parkinson’s Disease is of particular interest as gastrointestinal involvement is one of the earlier features seen in this disease. This paper examines the relationship between gut microbiota and Parkinson’s Disease, which has a growing body of literature. Inflammation caused by gut dysbiosis is thought to increase a-synuclein aggregation and worsen motor and neurologic symptoms of Parkinson’s disease. We discuss potential treatment and supplementation to modify the microbiota. Some of these treatments require further research before recommendations can be made, such as cord blood transplant, antibiotic use, immunomodulation and fecal microbiota transplant. Other interventions, such as increasing dietary fiber, polyphenol and fermented food intake, can be made with few risks and may have some benefit for symptom relief and speed of disease progression.

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Antibiotics at birth and later antibiotic courses: effects on gut microbiota

Pediatric Research ◽

10.1038/s41390-021-01494-7 ◽

2021 ◽

Author(s):

Sofia Ainonen ◽

Mysore V Tejesvi ◽

Md. Rayhan Mahmud ◽

Niko Paalanne ◽

Tytti Pokka ◽

...

Keyword(s):

Gut Microbiota ◽

Control Group ◽

List Type ◽

Antibiotic Exposure ◽

Microbiota Composition ◽

Long Term Effects ◽

The Impact ◽

Antibiotic Courses ◽

Gut Microbiota Composition

Abstract Background Intrapartum antibiotic prophylaxis (IAP) is widely used, but the evidence of the long-term effects on the gut microbiota and subsequent health of children is limited. Here, we compared the impacts of perinatal antibiotic exposure and later courses of antibiotic courses on gut microbiota. Methods This was a prospective, controlled cohort study among 100 vaginally delivered infants with different perinatal antibiotic exposures: control (27), IAP (27), postnatal antibiotics (24), and IAP and postnatal antibiotics (22). At 1 year of age, we performed next-generation sequencing of the bacterial 16S ribosomal RNA gene of fecal samples. Results Exposure to the perinatal antibiotics had a clear impact on the gut microbiota. The abundance of the Bacteroidetes phylum was significantly higher in the control group, whereas the relative abundance of Escherichia coli was significantly lower in the control group. The impact of the perinatal antibiotics on the gut microbiota composition was greater than exposure to later courses of antibiotics (28% of participants). Conclusions Perinatal antibiotic exposure had a marked impact on the gut microbiota at the age of 1 year. The timing of the antibiotic exposure appears to be the critical factor for the changes observed in the gut microbiota. Impact Infants are commonly exposed to IAP and postnatal antibiotics, and later to courses of antibiotics during the first year of life. Perinatal antibiotics have been associated with an altered gut microbiota during the first months of life, whereas the evidence regarding the long-term impact is more limited. Perinatal antibiotic exposure had a marked impact on the infant’s gut microbiota at 1 year of age. Impact of the perinatal antibiotics on the gut microbiota composition was greater than that of the later courses of antibiotics at the age of 1 year.

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Pulmonary and intestinal microbiota dynamics during Gram-negative pneumonia-derived sepsis

Intensive Care Medicine Experimental ◽

10.1186/s40635-021-00398-4 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Nora S. Wolff ◽

Max C. Jacobs ◽

W. Joost Wiersinga ◽

Floor Hugenholtz

Keyword(s):

Gut Microbiota ◽

Pulmonary Inflammation ◽

Alpha Diversity ◽

Severe Pneumonia ◽

Fecal Microbiota ◽

Protective Role ◽

Oral Microbiota ◽

Post Inoculation ◽

Systemic Spread ◽

Pathogen Burden

Abstract Background The gut microbiome plays a protective role in the host defense against pneumonia. The composition of the lung microbiota has been shown to be predictive of clinical outcome in critically ill patients. However, the dynamics of the lung and gut microbiota composition over time during severe pneumonia remains ill defined. We used a mouse model of pneumonia-derived sepsis caused by Klebsiella pneumoniae in order to follow the pathogen burden as well as the composition of the lung, tongue and fecal microbiota from local infection towards systemic spread. Results Already at 6 h post-inoculation with K. pneumoniae, marked changes in the lung microbiota were seen. The alpha diversity of the lung microbiota did not change throughout the infection, whereas the beta diversity did. A shift between the prominent lung microbiota members of Streptococcus and Klebsiella was seen from 12 h onwards and was most pronounced at 18 h post-inoculation (PI) which was also reflected in the release of pro-inflammatory cytokines indicating severe pulmonary inflammation. Around 18 h PI, K. pneumoniae bacteremia was observed together with a systemic inflammatory response. The composition of the tongue microbiota was not affected during infection, even at 18–30 h PI when K. pneumoniae had become the dominant bacterium in the lung. Moreover, we observed differences in the gut microbiota during pulmonary infection. The gut microbiota contributed to the lung microbiota at 12 h PI, however, this decreased at a later stage of the infection. Conclusions At 18 h PI, K. pneumoniae was the dominant member in the lung microbiota. The lung microbiota profiles were significantly explained by the lung K. pneumoniae bacterial counts and Klebsiella and Streptococcus were correlating with the measured cytokine levels in the lung and/or blood. The oral microbiota in mice, however, was not influenced by the severity of murine pneumonia, whereas the gut microbiota was affected. This study is of significance for future studies investigating the role of the lung microbiota during pneumonia and sepsis.

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Fecal Microbiota Transplant in Two Ulcerative Colitis Pediatric Cases: Gut Microbiota and Clinical Course Correlations

Microorganisms ◽

10.3390/microorganisms8101486 ◽

2020 ◽

Vol 8 (10) ◽

pp. 1486

Author(s):

Andrea Quagliariello ◽

Federica Del Chierico ◽

Sofia Reddel ◽

Alessandra Russo ◽

Andrea Onetti Muda ◽

...

Keyword(s):

Ulcerative Colitis ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Clinical Effects ◽

Phylogenetic Distance ◽

Fecal Microbiota Transplant ◽

Inflammatory Bowel ◽

Clinical Conditions ◽

And Control

Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts’ time-point profiles, donors and control cohorts’ baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient’s condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.

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IMPACT OF COGNITIVE DYSFUNCTION AND ROLE OF PHYSICAL EXERCISES TO ENHANCE COGNITIVE FUNCTIONS AMONG SUBJECTS WITH TYPE 2 DIABETES MELLITUS

10.36106/5336413 ◽

2021 ◽

pp. 47-48

Author(s):

Manju Unnikrishnan ◽

Titto Cherian

Keyword(s):

Type 2 Diabetes ◽

Cognitive Impairment ◽

Cognitive Ability ◽

Physical Performance ◽

Cognitive Functions ◽

Mortality And Morbidity ◽

Causes Of Mortality

Diabetes has become a widespread epidemic, characterized by hyperglycemia resulting from an error in insulin secretion, insulin action, or both, and is one of the leading causes of mortality and morbidity worldwide. Studies reveal that diabetes is linked to long-term complications in the brain, which appear in the form of impaired cognitive ability compared to people without diabetes( Van Duinkerken et al 2020). Reduced physical performance is one of the most important problems faced by patients which has a direct relationship with an individual's cognitive ability. The study aims to analyse the direct and positive relationship between physical exercise and cognitive functions among people with type 2 diabetes, so this must be veried along with gaining a comprehensive understanding of cognitive impairment in diabetes and its effect on physical performance. vice versa. This study is based on the reviewed research results of various researchers. In this study, the term "cognitive impairment" in relation to diabetes refers to any deviation in cognitive performance compared to people without diabetes.

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Impact of a Model Used to Simulate Chronic Socio-Environmental Stressors Encountered during Spaceflight on Murine Intestinal Microbiota

International Journal of Molecular Sciences ◽

10.3390/ijms21217863 ◽

2020 ◽

Vol 21 (21) ◽

pp. 7863

Author(s):

Corentine Alauzet ◽

Lisiane Cunat ◽

Maxime Wack ◽

Laurence Lanfumey ◽

Christine Legrand-Frossi ◽

...

Keyword(s):

Gut Microbiota ◽

Intestinal Microbiota ◽

Space Mission ◽

Psychosocial Stressors ◽

Mild Stress ◽

Protective Properties ◽

Β Diversity ◽

Intestinal Dysbiosis ◽

The Impact

During deep-space travels, crewmembers face various physical and psychosocial stressors that could alter gut microbiota composition. Since it is well known that intestinal dysbiosis is involved in the onset or exacerbation of several disorders, the aim of this study was to evaluate changes in intestinal microbiota in a murine model used to mimic chronic psychosocial stressors encountered during a long-term space mission. We demonstrate that 3 weeks of exposure to this model (called CUMS for Chronic Unpredictable Mild Stress) induce significant change in intracaecal β-diversity characterized by an important increase of the Firmicutes/Bacteroidetes ratio. These alterations are associated with a decrease of Porphyromonadaceae, particularly of the genus Barnesiella, a major member of gut microbiota in mice and humans where it is described as having protective properties. These results raise the question of the impact of stress-induced decrease of beneficial taxa, support recent data deduced from in-flight experimentations and other ground-based models, and emphasize the critical need for further studies exploring the impact of spaceflight on intestinal microbiota in order to propose strategies to countermeasure spaceflight-associated dysbiosis and its consequences on health.

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