Possible Role of the Antibiotic-Modified Microbiome in the Development of Hematological Malignancies in European Countries

Hematological malignancies are considered the fifth most common cancer in the world. Several risk factors and probable etiological agents have been suspected in the pathomechanism of those malignancies as infections, chemicals, irradiation, etc., and recently, the contribution of the altered gut flora, dysbiosis, was identified also as a possible additional factor to the existing ones. Host, and external factors, like antibiotics, which were identified as a major disruptor of the "normal" gut flora, influence the composition of the microbiome. Considering the several-fold differences in antibiotic consumption patterns and the incidence of hematological malignancies in European countries, the hypothesis was raised that the dominant consumption of certain antibiotic classes might influence the incidence of different hematological malignancies through the modification of gut flora. Comparisons were performed between the average antibiotic consumption databases reported yearly by ECDC (2009-2019) and the incidence rate of Hodkin lymphoma (HL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), and leukemia (LEU) estimated for 2020 in 30 European countries. Applying Spearman calculations, significant positive correlation has been found between the incidence of HL and tetracycline (J01A) consumption (r = 0.399, p = 0,029), NHL and narrow spectrum, beta-lactamase resistant penicillin (J01CF) (r = 0.580, p = 0,001), MM and tetracycline (r = 0.492, p = 0.006), penicillin (J01C) (r = 0.366, p = 0.047), narrow spectrum, beta-lactamase resistant penicillin (J01CF) (r = 0.574, p = 0.001), while strong, significant negative correlation has been recorded between NHL and cephalosporin (r = -0,460, p = 0,011), and quinolone (r = -0,380, p = 0,038). The incidence of LEU did not show any positive or negative association with any antibiotic classes. It is concluded that certain antibiotic classes, in addition to other putative factors, might promote or inhibit the development of different hematological malignancies.

Regulation of the intestinal dysbiosis of high – fat diet obese mice via gut microbia–TLR2 / 4 pathway by electroacupuncture

Objective: We design experimental study to explore the impacts of electroacupuncture (EA) treatment on the interaction between TLR2 / 4 pathway and gut flora in high – fat diet obese mice. Methods: Reverse transcriptase polymerase chain reaction, western blotting and 16S rRNA pyrosequencing were to study the association among groups (normal (N), model (M), electroacupuncture for 7 d (A7), 14 d (A14), 21 d (A21) and 28 d (A28) group). Results: EA reduced the relative expression of TLR2 / 4 gene and protein, and regulated the significant difference species flora in different levels, such as Firmicutes and Actinobacteria in Phylum, Coriobacteriia in Class, Coriobacteriales in Order, Atopobiaceae in Family, and Oscillibacter, Intestinimonas, Lachniclostridium and Acetatifactor in Genus. In all acupuncture groups, the analytical data of A21 group was similar to normal mice. Conclusion: These findings suggested the interaction between TLR2/ 4 pathway and gut flora could be a novel target of EA treatment against obesity.

Long COVID a New Derivative in the Chaos of SARS-CoV-2 Infection: The Emergent Pandemic?

Coronavirus disease 2019 (COVID-19) is a multisystem illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which can manifest with a multitude of symptoms in the setting of end-organ damage, though it is predominantly respiratory. However, various symptoms may remain after acute SARS-CoV-2 infection, and this condition is referred to as “Long COVID” (LC). Patients with LC may develop multi-organ symptom complex that remains 4–12 weeks after the acute phase of illness, with symptoms intermittently persisting over time. The main symptoms are fatigue, post-exertional malaise, cognitive dysfunction, and limitation of functional capacity. Pediatric patients developed the main symptoms of LC like those described in adults, although there may be variable presentations of LC in children. The underlying mechanisms of LC are not clearly known, although they may involve pathophysiological changes generated by virus persistence, immunological alterations secondary to virus–host interaction, tissue damage of inflammatory origin and hyperactivation of coagulation. Risk factors for developing LC would be female sex, more than five early symptoms, early dyspnea, previous psychiatric disorders, and alterations in immunological, inflammatory and coagulation parameters. There is currently no specific treatment for LC, but it could include pharmacological treatments to treat symptoms, supplements to restore nutritional, metabolic, and gut flora balance, and functional treatments for the most disabling symptoms. In summary, this study aims to show the scientific community the current knowledge of LC.

Lessons in clinical reasoning ‒ pitfalls, myths and pearls: a case of recurrent pancreatitis

Objectives Cognitive biases can result in clinical reasoning failures that can lead to diagnostic errors. Autobrewery syndrome is a rare, but likely underdiagnosed, condition in which gut flora ferment glucose, producing ethanol. It most frequently presents with unexplained episodes of inebriation, though more case studies are necessary to better characterize the syndrome. Case presentation This is a case of a 41-year old male with a past medical history notable only for frequent sinus infections, who presented with recurrent episodes of acute pancreatitis. In the week prior to his first episode of pancreatitis, he consumed four beers, an increase from his baseline of 1–2 drinks per month. At home, he had several episodes of confusion, which he attributed to fatigue. He underwent laparoscopic cholecystectomy and testing for genetic and autoimmune causes of pancreatitis, which were non-revealing. He was hospitalized 10 more times during that 9-month period for acute pancreatitis with elevated transaminases. During these admissions, he had elevated triglycerides requiring an insulin drip and elevated alcohol level despite abstaining from alcohol for the prior eight months. His alcohol level increased after consumption of complex carbohydrates, confirming the diagnosis of autobrewery syndrome. Conclusions Through integrated commentary on the diagnostic reasoning process, this case underscores how overconfidence can lead to premature closure and anchoring resulting in diagnostic error. Using a metacognitive overview, case discussants describe the importance of structured reflection and a standardized approach to early hypothesis generation to navigate these cognitive biases.

Gut Microbiota and SCFAs Play Key Roles in QingFei Yin Recipe Anti-Streptococcal Pneumonia Effects

Emerging evidence has revealed the presence in animals of a bidirectional regulatory “lung-gut axis” that provides resistance to respiratory infections. Clues to the existence of this system stem from observations that respiratory infections are often accompanied by gastrointestinal symptoms, whereby intestinal microbiota appear to play pivotal roles in combating pathogenic infections. Importantly, short-chain fatty acids (SCFAs) produced by the gut microbiota appear to serve as the biological link between host immune defenses and gut flora. Streptococcus pneumoniae (S.pn), the main cause of lower respiratory tract infections, is involved in more than 1.189 million deaths per year. QingFei Yin (QFY) is known for its excellent therapeutic efficacy in combating bacterial lung infections. In this study, effects of S.pn infection on gut homeostasis were assessed using 16S RNA-based microbiota community profiling analysis. In addition, potential mechanisms underlying QFY recipe beneficial therapeutic effects against bacterial pneumonia were explored using S.pn-infected gut microbiota-depleted mice. Results of data analysis indicated that QFY treatment alleviated lung infection-associated pathogenic processes, while also promoting repair of disordered gut flora and counteracting S.pn infection-associated decreases in levels of SCFAs, particularly of acetate and butyrate. Mechanistically, QFY treatment suppressed inflammatory lung injury through inhibition of the host NF-κB-NLRP3 pathway. These results inspired us to identify precise QFY targets and mechanisms underlying QFY anti-inflammatory effects. In addition, we conducted an in-depth evaluation of QFY as a potential treatment for bacterial pneumonia.

Probing Gut-Brain Links in Alzheimer's Disease with Rifaximin

Gut-microbiome-inflammation interactions have been linked to neurodegeneration in Alzheimers disease (AD) and other disorders. We hypothesized that treatment with rifaximin, a minimally absorbed gut-specific antibiotic, may modify the neurodegenerative process by changing gut flora and reducing neurotoxic microbial drivers of inflammation. In a pilot, open-label trial, we treated 10 subjects with mild to moderate probable AD dementia (MMSE = 17 + 3) with rifaximin for 3 months. Treatment was associated with a significant reduction in serum neurofilament-light levels (p <0.004) and a significant increase in fecal phylum Firmicutes microbiota. Serum pTau181 and GFAP levels were reduced (effect sizes of -0.41 and -0.48 respectively) but did not reach significance. There was also a non-significant downward trend in serum cytokine IL-6 and IL-13 levels. Increases in stool Erysipelatoclostridium were correlated significantly with reductions in serum pTau 181 and serum GFAP. Insights from this pilot trial are being used to design a larger placebo-controlled clinical trial to determine if specific microbial flora/products underlie neurodegeneration, and whether rifaximin is clinically efficacious as a therapeutic.

Gut Metabolite Trimethylamine-N-Oxide in Atherosclerosis: From Mechanism to Therapy

Atherosclerosis is associated with various pathological manifestations, such as ischemic heart disease, ischemic stroke, and peripheral arterial disease, and remains a leading cause of public health concern. Atherosclerosis is an inflammatory disease characterized by endothelial dysfunction; vascular inflammation; and the deposition of lipids, cholesterol, calcium, and cellular debris within the vessel wall intima. In-depth studies of gut flora in recent years have shown that bacterial translocation and the existence of bacterial active products in blood circulation can affect the inflammatory state of the whole blood vessel. The gut flora is considered to be a large “secretory organ,” which produces trimethylamine-N-oxide (TMAO), short-chain fatty acids and secondary bile acids by breaking down the ingested food. Studies have shown that TMAO is an independent risk factor for the occurrence of malignant adverse cardiovascular events, but whether it is harmful or beneficial to patients with cardiovascular diseases with mild or no clinical manifestations remains controversial. We review the relationship between TMAO and its precursor (L-carnitine) and coronary atherosclerosis and summarize the potential molecular mechanism and therapeutic measures of TMAO on coronary atherosclerosis.

Microbial Response to Fungal Infection in a Fungus-Growing Termite, Odontotermes formosanus (Shiraki)

The crosstalk between gut microbiota and host immunity has emerged as one of the research foci of microbiome studies in recent years. The purpose of this study was to determine how gut microbes respond to fungal infection in termites, given their reliance on gut symbionts for food intake as well as maintaining host health. Here, we used Metarhizium robertsii, an entomopathogenic fungus, to infect Odontotermes formosanus, a fungus-growing termite in the family Termitidae, and documented changes in host gut microbiota via a combination of bacterial 16S rDNA sequencing, metagenomic shotgun sequencing, and transmission electron microscopy. Our analyses found that when challenged with Metarhizium, the termite gut showed reduced microbial diversity within the first 12 h of fungal infection and then recovered and even surpassed pre-infection flora levels. These combined results shed light on the role of gut flora in maintaining homeostasis and immune homeostasis in the host, and the impact of gut flora dysbiosis on host susceptibility to infection.

Biogenic action of Lactobacillus plantarum SBT2227 promotes sleep in Drosophila melanogaster

Lactic acid bacteria (LAB) influence multiple aspects of host brain function via the production of active metabolites in the gut, which is known as the pre/pro-biotic action. However, little is known about the biogenic effects of LAB on host brain function. Here, we reported that the Lactobacillus plantarum SBT2227 promoted sleep in Drosophila melanogaster. Administration of SBT2227 primarily increased the amount of sleep and decreased sleep latency at the beginning of night-time. The sleep-promoting effects of SBT2227 were independent of the existing gut flora. Furthermore, heat treatment or mechanical crushing of SBT2227 did not suppress the sleep-promoting effects, indicative of biogenic action. Transcriptome analysis, and RNAi mini-screening for gut-derived peptide hormones revealed the requirement of neuropeptide F, a homologue of the mammalian neuropeptide Y, for the action of SBT2227. These biogenic effects of SBT2227 on the host sleep provide new insights into the interaction between the brain and gut bacteria.

- EU Harmonised Surveillance of Antimicrobial Resistance (AMR) in E. coli from Retail Meats in UK (2020 - Year 6, chicken)

In accordance with European Directive 2003/99/EC on the monitoring of bacteria that can pass from animals to humans and cause disease, Member States are obliged to ensure that procedures are in place to monitor and report on the occurrence of antimicrobial resistance (AMR) in such bacteria. The UK continued to be subject to EU rules during the transition period up to the end of December 2020. The requirements state that 300 retail chicken meats should be tested by culture for the bacterium Escherichia coli. E. coli bacteria are a normal part of the gut flora of mammals and as such can be useful “indicators” of AMR in gut bacteria. Whilst some strains of E. coli can cause disease, most strains of E. coli do not cause observable disease in healthy animals and humans. Addressing the public health threat posed by AMR is a national strategic priority for the UK, which has led to both a 20-year vision of AMR (Opens in a new window)and a 5-year (2019 to 2024) AMR National Action Plan (NAP)