Gut Check

Clinical Papers

A randomized controlled trial of the efficacy of systemic enzymes and probiotics in the resolution of post-COVID fatigue

Muscle fatigue and cognitive disturbances persist in patients after recovery from acuteCOVID-19 disease. However, there are no specific treatments for post-COVID fatigue. Objective: Toevaluate the efficacy and safety of the health supplements ImmunoSEB (systemic enzyme complex)and ProbioSEB CSC3 (probiotic complex) in patients suffering from COVID-19 induced fatigue.A randomized, multicentric, double blind, placebo-controlled trial was conducted in 200 patientswith a complaint of post-COVID fatigue. The test arm (n= 100) received the oral supplements for14 days and the control arm (n= 100) received a placebo. Treatment efficacy was compared usingthe Chalder Fatigue scale (CFQ-11), at various time points from days 1 to 14. The supplementaltreatment resulted in resolution of fatigue in a greater percentage of subjects in the test vs. the controlarm (91% vs. 15%) on day 14. Subjects in the test arm showed a significantly greater reductionin total as well as physical and mental fatigue scores at all time points vs. the control arm. Thesupplements were well tolerated with no adverse events reported. This study demonstrates that a14 days supplementation of ImmunoSEB + ProbioSEB CSC3 resolves post-COVID-19 fatigue and canimprove patients’ functional status and quality of life.

Diet, microbiome, and cancer immunotherapy—A comprehensive review

This review shows that specific dietary patterns (such as, e.g., animal-based, vegetarian, or Mediterranean diet) alter the gut microbiome’s composition. An appropriate intestinal microbiota structure might modulate the function of human immune system, which affects the bodily anti-cancer response. This paper shows also that specific bacteria species inhabiting the gastrointestinal tract can have a beneficial influence on the efficacy of immunotherapy. Antibiotics weaken gut bacteria and worsen the immune checkpoint blockers’ efficacy, whereas a faecal microbiota transplant or probiotics supplementation may help restore bacterial balance in the intestine. Other factors (like vitamins, glucose, or BMI) change the cancer treatment response, as well. This review demonstrates that there is a strong association between one’s diet, gut microbiome composition, and the outcome of immunotherapy. However, further investigation on this subject is required.

Gut microbiome diversity is an independent predictor of survival in cervical cancer patients receiving chemoradiation

Our results indicate that overweight or obesity is a favorable prognostic factor independent of gut diversity. In addition, our results demonstrate that patients with better clinical survival exhibit higher diversity as well as a distinct gut microbiome composition. At last, the association between gut diversity and local immune signatures suggests that patients with high gut diversity develop increased infiltration of activated CD4+ T-cell subsets and highlights helper CD4+ T cells as potential mediators of antitumor immunity upon CRT treatment.

Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients

We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. In conclusion, FMT from CR donors and re-induction of anti-PD-1 therapy in refractory metastatic melanoma patients was safe and feasible. In some patients, this treatment increased the intra-tumoral immune activity, which was translated into objective clinical responses. These findings support the concept of overcoming resistance to immunotherapy by modulating the gut microbiota.

Impact of microbial metabolites on microbiota-gut-brain axis in inflammatory bowel disease

This review highlights the more recent evidence suggesting that alterations of the microbiota–gut–brain bidirectional communication axis may concur to IBD pathogenesis and sustain the development of both local and CNS symptoms. The participation of the main microbial-derived metabolites, also defined as “postbiotics”, such as bile acids, short-chain fatty acids, and tryptophan metabolites in the development of IBD-associated gut and brain dysfunction will be discussed. Changes in gut-brain axis communication may contribute to the development of chronic visceral pain and hypersensitivity, representing the most common cause of disability and impaired quality of life in IBD.

Gut microbiota influence tumor development and alter interactions with the human immune system

Dysregulation of the gut microbiota and its interaction with the host may be important in tumorigenesis. Gut microorganisms and their toxic metabolites may migrate to other parts of the body via the circulatory system, causing an imbalance in the physiological status of the host and secretion of various neuroactive molecules through the gut-brain axis, gut-hepatic axis, and gut-lung axis to affect inflammation and tumorigenesis in specific organs. Thus, gut microbiota can be used as a tumor marker and may provide new insights into the pathogenesis of malignant tumors.

Role of probiotics in modulating human gut microbiota populations and activities in patients with colorectal cancer – A systematic review of clinical trials

Background: Growing attention has been given to the role of nutrition and alterations
of microbial diversity of the gut microbiota in colorectal cancer (CRC) pathogenesis. It has been suggested that probiotics and synbiotics modulate enteric microbiota and therefore may be used as an intervention to reduce the risk of CRC. The aim of this study was to evaluate the influence of probiotics/synbiotics administration on gut microbiota in patients with CRC. Methods: PubMed, Scopus, and Web of Science were searched between December 2020 and January 2021. Randomized controlled trials (RCTs) recruiting adults with CRC, who have taken probiotics/synbiotics for at least 6 days were included. Changes in gut microbiota and selected biochemical and inflammatory parameters (i.e., hsCRP, IL-2, hemoglobin) were retrieved. Results: The search resulted in 198 original research articles and a final 6 were selected as being eligible, including 457 subjects. The median age of patients was 65.4 years old and they were characterized by the median BMI value: 23.8 kg/m2. The literature search revealed that probiotic/synbiotic administration improved enteric microbiota by increasing the abundance of beneficial bacteria such as Lactobacillus, Eubacterium, Peptostreptococcus, Bacillus and Bifidobacterium, and decreased the abundance of potentially harmful bacteria such as Fusobacterium, Porhyromonas, Pseudomonas and Enterococcus. Additionally, probiotic/synbiotic intervention improved release of antimicrobials, intestinal permeability, tight junction function in CRC patients. Conclusions: The use of probiotics/synbiotics positively modulates enteric microbiota, improves postoperative outcomes, gut barrier function and reduces inflammatory parameters in patients suffering from CRC.

Altered gut microbial metabolites in amnestic mild cognitive impairment and Alzheimer’s disease: Signals in host–microbe interplay

This recent study identified an altered microbiome in patients with pre-onset amnestic mild cognitive impairment (aMCI) and dementia Alzheimer’s disease (AD). We identified significant differences between AD and HC for tryptophan metabolites, short-chain fatty acids (SCFAs), and lithocholic acid, the majority of which correlated with altered microbiota and cognitive impairment. Notably, tryptophan disorders presented in aMCI and SCFAs decreased progressively from aMCI to AD. Importantly, indole-3-pyruvic acid, a metabolite from tryptophan, was identified as a signature for discrimination and prediction of AD, and five SCFAs for pre-onset and progression of AD. This study showed fecal-based gut microbial signatures were associated with the presence and progression of AD, providing a potential target for microbiota or dietary intervention in AD prevention and support for the host–microbe crosstalk signals in AD pathophysiology.

Modulatory effects of the gut microbiome in cancer immunotherapy: A novel paradigm for blockade of immune checkpoint inhibitors

Notably, intestinal microbiota can cooperate with immune checkpoint inhibitors (ICIs) of its host, especially in enhanc-ing the efficacy of programmed death 1 (PD-1) protein and its ligand programmed death ligand 1 (PD-L1) blockade therapy for cancer. Herein, we review the dual function of gut microbiota in triggering GI cancers, its association with host immunity and its beneficial functions in modulation of cancer immunotherapy responses. Importantly, supplementation with specific probiotics or prebiotics and restoring the favorable intestinal microbi-ome by applying FMT or the prevention of the unfavorable bacteria by narrow-spectrum antibiotics may improve the effectiveness of ICIs in tumor control.

Postbiotics: A novel strategy in food allergy treatment

During the last two decades, the prevalence and severity of clinical appearances of food allergy (FA) have a significant rise. FA derives from a breakdown of immune tolerance. In recent year’s clinical evidence have shown that the probiotics have significant influences on FA by improving the immune tolerance. Besides, postbiotics due to their unique characteristics (safe profile, more shelf life, resistance to mammalian enzymes and stable to digestive system conditions), may have safety superiority against their parent live cells and as a novel strategy can be applied for improvement immune tolerance and treatment of FA without any undesirable side-effects or human opportunistic infections, particularly in infants and pediatrics.