Clinical Trials of Lactoferrin in the Newborn: Effects on Infection and the Gut Microbiome

2020 ◽  
pp. 1-11 ◽  
Author(s):  
Nicholas D. Embleton ◽  
Janet E. Berrington
Keyword(s):  
Clinical Trials ◽  
Gut Microbiome

scholarly journals The Oral β-Lactamase SYN-004, Designed to Protect the Gut Microbiome from Biliary Excreted IV Antibiotics, Efficiently Degrades Intestinal Ceftriaxone in Two Phase 2a Clinical Trials

2016 ◽  
Vol 3 (suppl_1) ◽  
Author(s):  
John Kokai-Kun ◽  
Tracey Roberts ◽  
Eric Sicard ◽  
Marianne Rufiange ◽  
Richard Fedorak ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Gut Microbiome ◽  
Two Phase

Probiotics for Mental Health: A Review of Recent Clinical Trials

2021 ◽  
pp. 155982762110491
Author(s):  
Monica Kazlausky Esquivel
Keyword(s):  
Mental Health ◽  
Clinical Trials ◽  
Nervous System ◽  
Gut Microbiome ◽  
Digestive System ◽  
Healthy Individuals ◽  
Appetite Control ◽  
Mental Health Benefits ◽  
Brain Neurotransmitters ◽  
Study Participants

The digestive system is involved in providing both regulatory and biochemical signaling to the nervous system via the gut–brain axis. Major brain neurotransmitters within the enteric nervous system include acetylcholine, serotonin, and norepinephrine, which are triggered by various stimuli within the digestive system, including the microbiota. Associations between the gut microbiome and activation of neuroreceptors and neurotransmitters are related to factors such as appetite control, mood, and memory. This column presents the results of a brief review of recently published clinical trials related to gut microbiome interventions (n = 11) that aimed to address a variety of mental health outcomes. The impacts of probiotics on mental health and other clinical outcomes vary by the health of study participants. Continuing research on the mental health benefits of probiotics in healthy individuals is necessary.

scholarly journals Is the Gut Microbiome a Target for Adjuvant Treatment of COVID-19?

Biologics ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 285-299
Author(s):  
Kai Hilpert
Keyword(s):  
Clinical Trials ◽  
Gut Microbiome ◽  
Transmembrane Protein ◽  
Meta Analysis ◽  
Gastrointestinal Symptoms ◽  
Control Group ◽  
Intestinal Damage ◽  
Pilot Studies ◽  
Mucosal Integrity ◽  
Probiotic Treatment

High expression of the transmembrane protein angiotensin I converting enzyme 2 (ACE2), more than 100-times higher as in the lung, and transmembrane serine protease 2 (TMPRSS2) in the gastrointestinal tract leads to infection with SARS-CoV-2. According to meta-analysis data, 9.8–20% of COVID-19 patients experience gastrointestinal symptoms, where diarrhoea is the most frequent, and about 50% shed viruses with high titre through their faeces, where a first faecal transmission was reported. Furthermore, gut inflammation, intestinal damage, and weakening of the gut mucosal integrity that leads to increased permeability has been shown in different studies for COVID-19 patients. This can lead to increased inflammation and bacteraemia. Low mucosal integrity combined with low intestinal damage is a good predictor for disease progression and submission to the intensive care unit (ICU). Several pilot studies have shown that the gut microbiome of COVID-19 patients is changed, microbial richness and diversity were lower, and opportunistic pathogens that can cause bacteraemia were enriched compared to a healthy control group. In a large proportion of these patients, dysbiosis was not resolved at discharge from the hospital and one study showed dysbiosis is still present after 3 months post COVID-19. Consequently, there might be a link between dysbiosis of the gut microbiome in COVID-19 patients and chronic COVID-19 syndrome (CCS). Various clinical trials are investigating the benefit of probiotics for acute COVID-19 patients, the majority of which have not reported results yet. However, two clinical trials have shown that a certain combination of probiotics is beneficial and safe for acute COVID-19 patients. Mortality was 11% for the probiotic treatment group, and 22% for the control group. Furthermore, for the probiotic group, symptoms cleared faster, and an 8-fold decreased risk of developing a respiratory failure was calculated. In conclusion, evidence is arising that inflammation, increased permeability, and microbiome dysbiosis in the gut occur in COVID-19 patients and thus provide new targets for adjuvant treatments of acute and chronic COVID-19. More research in this area is needed.

scholarly journals S3207 Time Trends in Gut Microbiome Clinical Trials in Gastroenterology

2020 ◽  
Vol 115 (1) ◽  
pp. S1681-S1682
Author(s):  
Gassan Kassim ◽  
Ryan Ungaro ◽  
David B. Sachar ◽  
Jean-Frederic Colombel ◽  
Eyal Klang
Keyword(s):  
Clinical Trials ◽  
Gut Microbiome ◽  
Time Trends

scholarly journals COVID-19 and the gut microbiome: more than a gut feeling

2020 ◽  
Author(s):  
Daniel van der Lelie ◽  
Safiyh Taghavi
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Gut Microbiome ◽  
Viral Infections ◽  
Intervention Strategies ◽  
Contributing Factors ◽  
Microbiome Composition ◽  
Clear Link ◽  
And Function ◽  
Druggable Targets

Due to its fundamental role in the induction, training, and function of the immune system, it is critical to include the gut microbiome in clinical trials and studies that aim to broaden our understanding of COVID-19. A clear link seems to exist between gut microbiome health and COVID-19 progression. Understanding the “gut-lung axes”, where gut microbiome composition influences the lung’s susceptibility to viral infections and viral infections of the lung alter gut microbiome composition toward proinflammatory functional dysbiosis will be critical in addressing COVID-19, including disease progression, the importance of preexisting conditions, and the risk for developing complications. These insights will help to identify biomarkers and druggable targets and develop intervention strategies based on live biotherapeutics and nutrition to overcome gut microbiome dysbiosis and restore intestinal homeostasis as contributing factors to COVID-19.

scholarly journals The role of the gut microbiome and exercise in non-alcoholic fatty liver disease

2020 ◽  
Vol 13 ◽  
pp. 175628482094174
Author(s):  
Veera Houttu ◽  
Ulrika Boulund ◽  
Aldo Grefhorst ◽  
Maarten R. Soeters ◽  
Sara-Joan Pinto-Sietsma ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Liver Disease ◽  
Fatty Liver ◽  
Gut Microbiome ◽  
Fatty Liver Disease ◽  
Inflammatory Responses ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

In recent years, the human gut microbiome has been found to influence a multitude of non-communicable diseases such as cardiovascular disease and metabolic syndrome, with its components type 2 diabetes mellitus and obesity. It is recognized to be mainly influenced by environmental factors, such as lifestyle, but also genetics may play a role. The interaction of gut microbiota and obesity has been widely studied, but in regard to non-alcoholic fatty liver disease (NAFLD) as a manifestation of obesity and insulin resistance, the causal role of the gut microbiome has not been fully established. The mechanisms by which the gut microbiome influences lipid accumulation, inflammatory responses, and occurrence of fibrosis in the liver are a topic of active research. In addition, the influence of exercise on gut microbiome composition is also being investigated. In clinical trials, exercise reduced hepatic steatosis independently of weight reduction. Other studies indicate that exercise may modulate the gut microbiome. This puts forward the question whether exercise could mediate its beneficial effects on NAFLD via changes in gut microbiome. Yet, the specific mechanisms underlying this potential connection are largely unknown. Thus, associative evidence from clinical trials, as well as mechanistic studies in vivo are called for to elucidate the relationship between exercise and the gut microbiome in NAFLD. Here, we review the current literature on exercise and the gut microbiome in NAFLD.

scholarly journals Nonclinical Safety Assessment of SYN-004

2015 ◽  
Vol 35 (3) ◽  
pp. 309-316 ◽  
Author(s):  
John F. Kokai-Kun ◽  
J. Andrew Bristol ◽  
John Setser ◽  
Michael Schlosser
Keyword(s):  
Clinical Trials ◽  
Gut Microbiome ◽  
Maximum Tolerated Dose ◽  
Systemic Absorption ◽  
High Dose ◽  
Noticeable Effect ◽  
Adverse Effect Level ◽  
Enteric Infections ◽  
Good Laboratory ◽  
Effect Level

SYN-004 is a first in class, recombinant β-lactamase that degrades β-lactam antibiotics and has been formulated to be administered orally to patients receiving intravenous β-lactam antibiotics including cephalosporins. SYN-004 is intended to degrade unmetabolized antibiotics excreted into the intestines and thus has the potential to protect the gut microbiome from disruption by these antibiotics. Protection of the gut microbiome is expected to protect against opportunistic enteric infections such as Clostridium difficile infection as well as antibiotic-associated diarrhea. In order to demonstrate that oral SYN-004 is safe for human clinical trials, 2 Good Laboratory Practice-compliant toxicity studies were conducted in Beagle dogs. In both studies, SYN-004 was administered orally 3 times per day up to the maximum tolerated dose of the formulation. In the first study, doses of SYN-004 administered over 28 days were safe and well tolerated in dogs with the no-observed-adverse-effect level at the high dose of 57 mg/kg/day. Systemic absorption of SYN-004 was minimal and sporadic and showed no accumulation during the study. In the second study, doses up to 57 mg/kg/day were administered to dogs in combination with an intravenous dose of ceftriaxone (300 mg/kg) given once per day for 14 days. Coadministration of oral SYN-004 with intravenous ceftriaxone was safe and well tolerated, with SYN-004 having no noticeable effect on the plasma pharmacokinetics of ceftriaxone. These preclinical studies demonstrate that SYN-004 is well tolerated and, when coadministered with ceftriaxone, does not interfere with its systemic pharmacokinetics. These data supported advancing SYN-004 into human clinical trials.

scholarly journals The Unique Impact of COVID-19 on Human Gut Microbiome Research

2021 ◽  
Vol 8 ◽  
Author(s):  
Ella Burchill ◽  
Eva Lymberopoulos ◽  
Elisa Menozzi ◽  
Sanjay Budhdeo ◽  
James R. McIlroy ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Gut Microbiome ◽  
Indirect Effects ◽  
Population Level ◽  
Faecal Microbiota ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Microbiome Research ◽  
Potential Impact

The coronavirus (COVID-19) pandemic has disrupted clinical trials globally, with unique implications for research into the human gut microbiome. In this mini-review, we explore the direct and indirect influences of the pandemic on the gut microbiome and how these can affect research and clinical trials. We explore the direct bidirectional relationships between the COVID-19 virus and the gut and lung microbiomes. We then consider the significant indirect effects of the pandemic, such as repeated lockdowns, increased hand hygiene, and changes to mood and diet, that could all lead to longstanding changes to the gut microbiome at an individual and a population level. Together, these changes may affect long term microbiome research, both in observational as well as in population studies, requiring urgent attention. Finally, we explore the unique implications for clinical trials using faecal microbiota transplants (FMT), which are increasingly investigated as potential treatments for a range of diseases. The pandemic introduces new barriers to participation in trials, while the direct and indirect effects laid out above can present a confounding factor. This affects recruitment and sample size, as well as study design and statistical analyses. Therefore, the potential impact of the pandemic on gut microbiome research is significant and needs to be specifically addressed by the research community and funders.

Nanobyte

2018 ◽  
Vol 3 (1) ◽  
pp. 1
Author(s):  
Radhika A. Vaishnav
Keyword(s):  
Clinical Trials ◽  
Gut Microbiome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Poor Responders ◽  
Microbiome Composition ◽  
Near Future ◽  
Immune Checkpoint Blockers

Immune checkpoint inhibitors targeting PD-1/PD-L1 can have differing effects in various individuals. Recent studies published have suggested a role in the gut microbiome composition in contributing to the efficacy of these drugs. Patients who took antibiotics showed a poorer response to PD-1 inhibitors compared to those who did not take any antibiotics. In another study, fecal transplants to mice from patients that improved on PD-1 blockers showed improvement on the drugs, while mice receiving transplants from poor responders showed similar lack of efficacy of PD-1 blockers. New clinical trials and metagenomics studies are anticipated in the near future that could allow us to understand better the mechanisms of the gut microbial role in the effectiveness of immune checkpoint blockers.

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