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(August, 2018)

There is mounting evidence for the contribution of endogenous microbes in chronic, age-related disease. Our human gut microbiome, comprised of a diverse and complex community of microorganisms, fluctuates appreciably at different stages of life. Perturbations in the gut microbiome could strongly impact host health and disease. Most deviations occur during infancy and old age, precisely when immune health is often suspect and unstable, so there may be a causal relationship. A recent review explores these age-associated changes in intestinal microbiota, and the development of interventions such as probiotics for healthy aging (Nagpal et al., 2018; Hill, 2018).

Depression and anxiety have also been linked to a gut bacteria imbalance. Irritable Bowel Syndrome (IBS) patients deal a lot with depression and anxiety. Supplementation with the probiotic Bacillus coagulans MTC 5856 (Sabinsa Corporation) was shown recently to ameliorate IBS-related symptoms. The probiotic reduced myeloperoxidase (MPO)–an enzyme that creates damaging free radicals and oxidative stress–significantly (Majeed et al., 2018). Post-partum depression also responded favorably to L. rhamnosus HN001 probiotic supplementation (Slykerman et al., 2017). A pilot study in humans suggests that depressive symptoms respond to a probiotic containing L. helveticus Rosell-52 and B. longum (Lallemand’s Probio’ Sticks), which has an approved ‘gut-brain axis’ health claim from Health Canada (Menayang, 2018). Probiotics may improve the integrity of the gastrointestinal lining and defend against intestinal permeability (leaky gut), which promotes leakage of inflammatory bacteria and toxins into the bloodstream. Probiotics also produce short-chain fatty acids, which support neurotransmitters, hormones, and immune substances, to help alleviate inflammation and depression. Our microbiome can play an important role in cognitive health and affective disorders.

Even resiliency relies on a healthy and diverse gut microbiota. Resiliency helps buffer against physiological and immune stresses. Resilient people tend to have more robust immune systems and more diverse microbiomes (Dantzer et al., 2018). A healthy diet also bolsters resilience, but part of that is soluble fiber, which feeds our gut microflora. Gut dysbiosis, from poor diet or antibiotics, can negatively affect mental state and resilience. Scientists are exploring the benefits of various gut microbes on resilience and immunity. Various Bifidobacteria and Lactobacilli species have shown anxiolytic and other favorable cognitive effects. Certain “psychobiotics”, along with a Mediterranean diet, can help fight stress and prevent depression. In contrast, substances like antibiotics, glyphosate, heartburn meds, halide-treated water, sugar, processed foods, and NSAIDs alter or lower microbiome diversity. Nutritional psychiatry is an emerging field of study (Dantzer et al., 2018).

One of the better drugs administered by physicians is metformin, the most widely prescribed drug to treat type II diabetes (Grant, 2018). Metformin’s glucose-lowering benefits have helped those with diabetes for more than 50 years (Bailey, 2017). Metformin increases beneficial metabolic regulators, which decline as we age. A recent study out of Johns Hopkins showed that metformin also boosts a beneficial gut bacterium called Akkermansia muciniphila (de la Cuesta-Zuluaga et al., 2017). Diabetic subjects who took metformin developed more A. muciniphila than all other groups. They also had higher levels of bacteria making short-chain fatty acids (e.g., butyrate), which have anti-inflammatory properties (Wang et al., 2017). Diabetics not taking metformin showed more toxic bacteria (Scarpa et al., 2011; de la Cuesta-Zuluaga et al., 2017). In a 12-week dietary intervention, Sorbonne researchers gave 49 overweight and obese adults six weeks of a calorie-restricted diet followed by six weeks of weight stabilization. Subjects with the highest baseline stool levels of A. muciniphila showed the lowest fasting blood glucose, weight-to-hip ratio, mean fat-cell diameter, and triglycerides, and had better body fat distribution. Higher levels of A. muciniphila correlated with the presence of other beneficial microbes (Dao et al., 2016). Another study showed metformin’s ability to improve a condition called leaky gut and its resultant low-grade inflammation (Lee, 2016; Zhou et al., 2016). Chronic inflammation can lead to insulin resistance and high blood-sugar (Lee, 2016). In further support, mice made insulin resistant with a high-fat diet were treated with metformin alone, or metformin following injections of gut-related, pro-inflammatory toxins (Zhou, 2017).  Metformin treatment reversed gut leakiness from the high-fat diet, lowered toxicity, and increased beneficial Lactobacillus  and Akkermansia numbers, helping to heal a dysbiotic gut. No wonder why metformin is such a good remedy for diabetes. Interventions that boost A. muciniphila and related organisms could prove useful in counteracting many chronic diseases of modernity.

It is becoming clear that our gut bacteria affect numerous biochemical and physiologic functions, in beneficial and deleterious ways. The data presented here are only those gathered this month on the topic. As more and more scientists study this burgeoning area of research, we get closer to finding answers for improving health and well-being, and aging more gracefully.

References

Bailey CJ. Metformin: historical overview. Diabetologia 2017;60(9):1566-76.

Dantzer R, Cohen S, Russo S, Dinan T. Resilience and immunity. Brain Behav Immun. 2018 Aug 10. pii: S0889-1591(18)30440-9. https://www.ncbi.nlm.nih.gov/pubmed/30102966

Dao MC, Everard A, Aron-Wisnewsky J, et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2016;65(3):426-36.

de la Cuesta-Zuluaga J, Mueller NT, Corrales-Agudelo V, et al. Metformin Is associated with higher relative abundance of mucin-degrading Akkermansia muciniphila and Several Short-Chain Fatty Acid-Producing Microbiota in the Gut. Diabetes Care. 2017;40(1):54-62.

Grant S. Metformin reduces diabetic risk by improving gut health. Life Extension Magazine September 2018. http://www.lifeextension.com/Magazine/2018/9/Metformin-Improves-Gut-Health/Page-01?sourcecode=CVH801E&utm_source=Zmag&utm_medium=email&utm_content=ReadMoreArticle5&utm_campaign=CVH801E

Lee MS. Ed 05-2: Interaction of gut dysbiosis and innate immune dysfunction in the development of metabolic syndrome. J Hypertens 2016;34 Suppl 1 2016:e187.

Majeed M, Nagabhushanam K, Arumugam S, et al. Bacillus coagulans MTCC 5856 for the management of major depression with irritable bowel syndrome: a randomised, doubleblind, placebo controlled, multi-centre, pilot clinical study. Food Nutrition Res 2018;62. https://foodandnutritionresearch.net/index.php/fnr/article/view/1218

Menayang A. Pilot study sheds light on probiotics’ potential as novel therapy for depression symptoms. NutraIngrediants-USA June 2018. https://www.nutraingredients-usa.com/Article/2018/06/18/Pilot-study-sheds-light-on-probiotics-potential-as-a-novel-therapeutic-for-depression-symptoms

Nagpal R, Mainali R, Ahmadi S, et al. Gut microbiome and aging: Physiological and mechanistic insights. Nutr Healthy Aging. 2018;4(4):267-85.

Scarpa M, Grillo A, Faggian D, et al. Relationship between mucosa-associated microbiota and inflammatory parameters in the ileal pouch after restorative proctocolectomy for ulcerative colitis. Surgery 2011;150(1):56-67.

Slykerman RF, Hood F, Wickens K, et al. Effect of Lactobacillus rhamnosus HN001 in pregnancy on postpartum symptoms of depression and anxiety: A randomized double-blind placebo-controlled trial. EBioMed 2017;24:159–65. 

Wang F, Liu J, Weng T, et al. The Inflammation Induced by lipopolysaccharide can be mitigated by short-chain fatty acid, butyrate, through upregulation of IL-10 in septic shock. Scand J Immunol 2017;85(4):258-63.

Zhou ZY, Ren LW, Zhan P, et al. Metformin exerts glucose-lowering action in high-fat fed mice via attenuating endotoxemia and enhancing insulin signaling. Acta Pharmacol Sin 2016;37(8):1063-75.

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