Microbiome

Antibiotic induced changes to mitochondria result in potential contributions to carcinogenesis, heart pathologies, other medical conditions and ecosystem risks

Published on: 2nd October, 2020

OCLC Number/Unique Identifier: 8689024240

With the discovery by Calghatgi (2013) that three common antibiotics (Abs) increased mitochondrial reactive oxygen (ROS) and lipid peroxide (LP) and depleted their natural absorbant glutathione led me to investigate further the potential impacts of these genotoxic substances on carcinogenesis. The range of impacts on mitochondria and cellular DNA varied by antibiotic to those consistent with known prior contributions to carcinogenesis. Specific cancers probably increased by these changes were HCC, RCC (KCC), CRC, cancer of the esophagus. Tumor suppressor gene mutations resulting from LP were noteworthy in this regard and mutations induced in CRC were consistent with those found in carcinogenesis of CRC. In addition depression of short chain fatty acids in microbiomes were found which depress the immune system increasing risk of all cancers. Many cancers were increased according to epidemiological studies linking Abs with elevated odds ratios, with one concern in particular, fatal breast cancer. The impact of loss of functionality of the mitochondria was also linked to depression of the citric acid cycle and therefore ATP which deflected metabolism to glycolysis, the Warburg mechanism also increasing risk of all cancers, favoured by cancer cells. In conclusion, some portion of many cancer types are probably increased in likelihood by number, type and frequency of Abs treatment and chronic residue exposure which varies from individual to individual. This led me to propose a three pronged carcinogenesis mechanism for Abs. 1. Cancer critical mutations 2. Immune depression 3. loss of mitochondrial functionality leading to Warburg effects. Damage to mitochondria were also noted by common pesticides tested in China and cancer associations were also found for many pesticides supporting a similar contributory etiology. Heart health concerns were raised by these findings because of the myriad mitochondria in the heart and because of long term reliability needs. Studies suggesting hearts were affected by Abs and pesticide exposure were presented. Because of their geographical ubiquitousness and the huge range of diseases associated with mitochondrial dysfunction, antibiotics and pesticides and bacteriocidal biocides are of concern for biodiversity and life in general. I propose research steps to evaluate Abs safety and suggest directions for further research and make suggestions on ways to ameliorate Abs toxicity.
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Recent findings related to Nutrition and Diabetes Mellitus

Published on: 18th February, 2018

OCLC Number/Unique Identifier: 7964755229

Roux-en-Y Gastric Bypass surgery is superior to medical treatment for short- to medium-term remission of Type 2 diabetes (T2DM) [1]. Recent research indicates that the improvements in insulin sensitivity following bariatric surgery are associated with elevated circulating bile acid concentration and remodeling of gut microbiota [2]. Gut microbiome can be considered as a target of dietary interventions or medicines to prevention/treatment of hyperglycemia in T2DM. Since, the glucose-lowering effects of metformin are mediated by changes in the composition and function of gut microbiota [3,4].
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Microbiome and Gastroesophageal Disease: Pathogenesis and Implications for Therapy

Published on: 21st May, 2020

OCLC Number/Unique Identifier: 8603898545

There is growing evidence that gastroesophageal disease is influenced by the esophageal microbiome, and that commensal bacteria of the oropharynx, stomach, and colon are thought to have a role in modulatiing pathogenesis. These emerging hypotheses are based on observed changes in the composition of the esophageal flora, notably, repeated observations: 1. There is an abundance of gram-positive bBacteria in the healthy esophagus. are more gram positive prevalent 2. The esophageal bacterial population becomes increasingly gram negative with disease progression. Associated with this shift to a more gram negative prevalence is an increase in the potential for the presence of antigenic lipopolysaccharide (LPS). The immunoreactivity of LPS endotoxin thought to promote susceptibility to inflammation and disease. The pathogenesis of the more common diseases of the esophagus e.g. gastroesophageal reflux disease (GERD), esophageal dysmotility (achalasia), eosinophilic esophagitis (EoE), Barrett’s esophagus (BE), and esophageal cancer, are well-established. Emerging data suggest however, that these are all characterized by an immune-mediated inflammatory cascade, propogated by a dysbiotic state. Thereby, the ability of the healthy “normative state” to protect against foreign bacteria is compromised. This dysbiosis thereby can create adverse inflammatory or immunoregulatory responses with progression of disease. In the normal healthy state, the esophageal microbiome is constituted in-part, by a multitude of gram positive bacteria, many of which produce antibacterial peptides called bacteriocins. Bacteriocins are selective and used to maintain population integrity by killing off foreign bacteria. When the “normative biome” is interrupted (e.g. antibiotics, medications, diet, environmental factors), the constitutional changes may allow a more hospitable imbalance favoring the proliferation of opportunistic pathogens. Therefore it seems rational that defining, perhaps that defining, perhaps cultivating, a protective bacterial community that could help prevent or mitigate inflammatory diseases of the esophagus. Furthermore, in conjunction with evidence demonstrating that some bacteriocins are cytotoxic or antiproliferative toward cancer cell lines, further exploration might provide a rich source of effective peptide-based drug targets. Therapeutic options targeting the microbiome, including prebiotics, probiotics, antibiotics and bacteriocins, have been studied, albeit the attributable effects on the esophagus for the most part, have been unrecognized by clinicians. This review focuses on the current knowledge of the involvement of the microbiome in esophageal diseases (most notably GERD/Barrett’s esophagus/esophageal cancer) and identifies emerging new concepts for treatment.
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Acute pancreatitis with uncommon presentation of myocardial infarction

Published on: 21st May, 2020

OCLC Number/Unique Identifier: 8616347855

Acute pancreatitis is inflammation of the pancreas that may be accompanied by a systemic inflammatory response which results in impairment of the functioning of various organs, systems. Pancreatitis associated vascular complications very often cause morbidity and mortality. There are various cardiovascular complications like shock, hypovolemia, pericardial effusion, and sometimes ST–T changes in the electrocardiogram (ECG) presenting as acute myocardial infarction (AMI). Acute myocardial infarction complicating acute pancreatitis has rarely been studied and the exact process of myocardial injury still remains unclear. We here report a case of Acute Pancreatitis associated with acute myocardial Infarction.
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Upper gut bacterial overgrowth is a potential mechanism for Glucose Malabsorption after Vertical Sleeve Gastrectomy

Published on: 31st October, 2017

OCLC Number/Unique Identifier: 7317655960

In 1955, nutrient malabsorption following upper gut surgery was shown to be related to altered upper gut microbiome. In individuals with abdominal symptoms after Roux-en-Y gastric bypass, we have reported that small intestinal glucose malabsorption is associated with upper gut bacterial overgrowth. We hypothesize that individuals with abdominal symptoms after vertical sleeve gastrectomy have glucose malabsorption associated with upper gut bacterial overgrowth, and to test this hypothesis, bacterial overgrowth and potential glucose malabsorption are examined after sleeve gastrectomy. This is a retrospective study of individuals with medically-complicated obesity who underwent sleeve gastrectomy from 2013 to 2016 with subsequent glucose hydrogen breath testing to evaluate abdominal symptoms. A fasting breath hydrogen or methane of ≥10 PPM or rise of ≥8 PPM ≤45 minutes after oral glucose is bacterial overgrowth, while glucose malabsorption is a second rise of ≥8 PPM at >45 minutes. Seven females (mean age: 48.0 years; mean body mass index at surgery: 45.7 kg/m2) are described. Five subjects (71%) have an early rise in hydrogen or methane, while three (43%) have a second rise in hydrogen or methane >45 minutes after glucose. The mean percent excess weight loss at one year was 40% in three individuals with a second peak and 46% in four subjects without a second peak. After sleeve gastrectomy, subjects have glucose malabsorption associated with the presence of bacterial overgrowth. Completion of a larger prospective study is needed to confirm and expanding upon these findings. Further work should examine the potential effects of bacterial overgrowth on expression of intestinal glucose transporters.
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Unveiling the gut virome in human health and diseases

Published on: 19th January, 2018

OCLC Number/Unique Identifier: 7814985079

Due to the advances in high-throughput sequencing technologies, the gut vriome is increasingly being perceived as one important component of the gut microbiome, where the number of viral biological entities is believed to far outcompetes that of the bacterial populations [1,2]. The human virome are primarily composed of bacteriophages, animal-cell viruses, endogenous retroviruses and viruses causing persistent and latent infections. Collectively they contains a more diverse genetic entity than the gut bacteria [3,4]. While the composition of them in the gut is precipitately being revealed, their roles in human health remain largely unexplored. It is undeniable that certain gut viruses are deleterious to human health. Interestingly, enteric viruses however, in some cases, can recapitulate the beneficial effects of commensal bacteria through different mechanisms, including modulating the innate and adaptive immunity of the host [5-7].
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Non-alcoholic fatty liver disease: Update on treatment options and translational implications of sleep disruption

Published on: 17th August, 2021

OCLC Number/Unique Identifier: 9206109721

Non-alcoholic fatty liver disease (NAFLD) is a condition that is associated with cirrhosis and hepatocellular carcinoma, and is increasing in prevalence worldwide. Sleep disruptions are commonly seen in NAFLD, and the disease process is associated with sleep disorders, including obstructive sleep apnea, circadian rhythm disorders, and insufficient sleep. The intermittent hypoxia seen in obstructive sleep apnea may contribute to fibrotic changes in the liver.A major component of this linkage may be related to gut microbiome changes. One notable change is increase in Bacteroidetes/Firmicutes ratio, and decrease in flora that ferment fiber into anti-inflammatory short-chain fatty acids. Several therapeutic options exist for NAFLD that target both sleep and NAFLD, including non-pharmacological factors, such as lifestyle modification (mainly diet and exercise). Pharmacological options include melatonin, Vitamin E, thiazolidinediones, and fecal microbiota transplantation.Core tipThe pathogenesis of non-alcoholic fatty liver disease is closely tied to sleep and circadian rhythm abnormalities, through shared inflammatory pathways and altered metabolism. This review explores the pathogenesis of NAFLD in the context of sleep and circadian abnormalities. The associated inflammatory response is linked to changes in gut-microbiome interactions that contribute to the disease process. Understanding of this linkage has implications for various therapies for disease mitigation.
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