This issue is dedicated to the microbiome. Studies pointing to its central role in health and disease are ubiquitous in our medical and nutritional journals. The microbiome’s impact is far reaching, even when it is not specifically mentioned. This is the missing point in the article below. See if you can deduce the microbiome’s involvement in said article, BEFORE you read the commentary.
Hugo Rodier, MD
Proton pump inhibitors and dementia
J. Alzheimer’s and Dementia, 2024;20:837-845
“After following 1,983,785 individuals for a median of 10 years, 99,384 developed dementia. PPIs were used by 21.2% of cases and 18.9% of controls. PPI use was associated with increased dementia rate regardless of time of treatment onset. Magnitude of associations increased with younger age at diagnosis. PPI use was not associated with dementia occurring after age 90 years.”
Comment: PPIs change the acidity of your gut, which foments inflammatory bacteria in the intestines. This leads to inflammatory changes in the brain. PPIs also curtail the digestion and absorption of micronutrients critical to brain function. This is why PPIs have been associated with a higher risk for heart disease.
Unraveling role of the gut microbiome in PCOS
Healio Minute, June 13 2024
“BOSTON — Evidence suggests hyperandrogenism is associated with changes in the gut microbiome in women with polycystic ovary syndrome and the gut microbiome may play a causal role in PCOS metabolic dysregulation. “While the gut microbiome is quite variable in humans due to diet and geographical influences, meta-analyses of human studies revealed that women with PCOS have a consistent decrease in biodiversity of gut microbiota and changes in specific bacteria, including Bacteroides, that are associated with hyperandrogenism,” Thackray, PhD, professor in the department of obstetrics, gynecology and reproductive sciences at the University of California, San Diego, [reported that] “mouse models of PCOS also indicate that these changes in the gut microbiome occur without any differences in diet, indicating that diet-independent factors are driving these changes. Altogether, these studies indicate that increased testosterone levels in women modulate the composition of gut microbiota and production of microbial metabolites, which can then influence the host and contribute to PCOS pathology.” Thackray said antibiotic depletion of the gut microbiome in a PCOS-like mouse model showed that the gut microbiome was required for parameters of metabolic dysregulation associated with type 2 diabetes risk, such as abdominal adiposity and insulin resistance. “This is surprising because it indicates that the gut microbiome may be required for certain aspects of PCOS metabolic dysregulation and provides an opportunity to develop microbial-based therapies for PCOS.”
Comment: this article also applies to women who are prediabetic, having menstrual problems, pregnancy (see below), and gaining weight. The basic problem is the overgrowth of inflammatory bacteria caused by too much sugar in the diet.
Sex hormones in the gut soar during pregnancy — thanks to busy bacteria
J. Nature May 31 2024
“Two species in the gut microbiome transform corticosteroids into progestins, which can affect mood and behavior.”
Comment: the microbiome also affects hormonal function directly. This is one of the mechanisms involved in the Brain-Gut axis. Among the others are inflammation from the gut to the brain, and metabolism in the gut. The brain is very sensitive to minor fluctuations of energy.
Metformin, Cognitive Function, and Changes in the Gut Microbiome
J. Endocrine Reviews, Volume 45, Issue 2, April 2024, Pages 210–226,
“The decline in cognitive function and the prevalence of neurodegenerative disorders are among the most serious threats to health in old age. The prevalence of dementia has reached 50 million people worldwide and has become a major public health problem. The causes of age-related cognitive impairment are multiple, complex, and difficult to determine. However, type 2 diabetes (T2D) is linked to an enhanced risk of cognitive impairment and dementia. Human studies have shown that patients with T2D exhibit dysbiosis of the gut microbiota. This dysbiosis may contribute to the development of insulin resistance and increased plasma lipopolysaccharide concentrations. Metformin medication mimics some of the benefits of calorie restriction and physical activity, such as greater insulin sensitivity and decreased cholesterol levels, and hence may also have a positive impact on aging in humans. According to recent human investigations, metformin might partially restore gut dysbiosis related to T2D. Likewise, some studies showed that metformin reduced the risk of dementia and improved cognition, although not all studies are concordant. Therefore, this review focused on those human studies describing the effects of metformin on the gut microbiome (specifically the changes in taxonomy, function, and circulating metabolomics), the changes in cognitive function, and their possible bidirectional implications.”
Comment: metformin, derived from the French Lilly, seems to have many salutary effects. No wonder—it works on the liver and the microbiome.
Microbes and vitamin D aid immunotherapy
J. SCIENCE 2024;384:384-385
“Tremendous progress has been made in improving cancer immunotherapy, which is now established as a pillar for cancer treatment. Immune checkpoint inhibitors (ICIs) enhance antitumoral T cell responses by blocking interactions of the inhibitory receptors cytotoxic T lymphocyte–associated protein 4 (CTLA-4) or programmed cell death protein 1 (PD-1) that are expressed on T cells with their ligands. ICIs are used to treat a variety of cancer types, including melanoma, non–small cell lung cancer, and renal cell carcinoma (1), with patients often displaying long-lasting responses. Nevertheless, a substantial proportion of patients do not respond to ICIs (1), and the gut microbiome has been identified as a key modulator of ICI effectiveness (2–4). Diet strongly influences gut microbial composition and function. On page 428 of this issue, Giampazolias et al. (5) report the identification of vitamin D as a dietary component involved in promoting microbial regulation of responses to ICI therapy in mice.”
Comment: vitamin D has previously been shown to optimize the microbiome, which is 2/3 of our immune-detoxification system. Most cancers are due to environmental issues. We put our best foot forward when we eat a lot of fruit and veggies, rich in prebiotics.
Association Between Adequate Serum 25(OH)D Levels and Atherogenic Dyslipidemia in Young Adults
J. Atherosclerosis Thrombosis 2024 Volume 31 Issue 5 Pages 524-539
“This study provides evidence of an association between vitamin D deficiency and atherogenic dyslipidemia in young adults. It further highlights that individuals with serum 25(OH)D levels below 30 ng/mL are at a significantly higher risk of developing atherogenic dyslipidemia in a dose–response manner compared to those with higher vitamin D levels. These findings underscore the potential role of vitamin D in dyslipidemia management and emphasize the importance of maintaining sufficient vitamin D levels for cardiovascular health in young adults.”
Comment: vitamin D is not really a vitamin; it’s a pro-hormone that acts on cell nuclear receptors. It optimizes how the microbiome processes foods. Read about postbiotics.
Unlocking the power of postbiotics: A revolutionary approach to nutrition for humans and animals
J. Cell Metabolism April 2 2024
“Postbiotics, which comprise inanimate microorganisms or their constituents, have recently gained significant attention for their potential health benefits. Extensive research on postbiotics has uncovered many beneficial effects on hosts, including antioxidant activity, immunomodulatory effects, gut microbiota modulation, and enhancement of epithelial barrier function. Although these features resemble those of probiotics, the stability and safety of postbiotics make them an appealing alternative. In this review, we provide a comprehensive summary of the latest research on postbiotics, emphasizing their positive impacts on both human and animal health. By substituting postbiotics for antibiotics, we can promote health and productivity while minimizing adverse effects. This alternative approach holds immense potential for improving health outcomes and revolutionizing the food and animal products industries.”
Comment: anything you put in your mouth, including chemicals and drugs, will be modulated by your microbiome into what we call a postbiotic. It is the final functional molecule.
