General and microbiological chronic diseases into humans

INTRODUCTION

In every country, non-communicable and CDs are currently the leading cause of adult mortality, and over the next ten years, this number is expected to rise by an additional 17%.¹ About one-third of persons worldwide suffer from several chronic illnesses.² Previous Indian research show that at least one chronic illness affects 21% of India's elderly population. Chronic disease affects 29% of older people in urban settings and 17% of senior people in rural areas. All chronic disorders, hypertension, and diabetes account for over 68%. Kerala (54%) has the highest rate of chronic disease prevalence, followed by Andhra Pradesh (43%) West Bengal (36%), and Goa (32%). In the US, four out of ten persons have two or more CDs, and six out of ten adults have one or more.³ An estimated 35 million of the 58 million fatalities that occurred in 2005 were predicted to be caused by chronic illnesses.¹ Several unhealthy behaviors, including smoking, non exercising, eating poorly, and drinking too much alcohol, are significant causes of the most common chronic illnesses.⁴ In developed nations, the most common chronic illnesses are CVD and arthritis. heart attacks and strokes, diabetes, cancer (breast, colon, and epilepsy), obesity, and issues with the mouth. Senior citizens are afflicted with all these ailments. The increase in CDs is a grave concern for public health as well as the impacted societies and economies. The effect and profile of CDs were usually underappreciated until recently.⁵

Microbes and humans interact in a variety of intricate ways. Since we now know that infectious agents can cause chronic illnesses and that the human microbiome plays a significant role in both health and disease, our understanding of the interactions between humans and microorganisms has undergone a fundamental shift. We are discovering that chronic disorders previously believed to be unrelated to infectious processes can also be caused by infectious agents. The world's most prevalent, expensive, and avoidable health issues, CDs have a staggering toll. Seven out of ten deaths annually are caused by CDs, which are also the major cause of disability and mortality. Each year, cancer, and CVD cause over half of all deaths.⁶

Many CDs are not caused by infections; instead, their causes can be hereditary, environmental toxins, the combination of several behavioural and other risk factors, or an unidentified factor. Numerous mechanisms exist for infectious pathogens to induce chronic illness. CDs including Chlamydia infection and CVD can be brought on by inflammation brought on by infections or the immune system's reaction to infections.⁷ Early infection can potentially result in long-term, irreversible impairments or deficiencies (e.g., paralysis following poliovirus infection). An indirect risk factor for chronic illness is infection; for example, a mother's sickness can put her offspring at risk for psychological problems. Finding the source of an infection that causes a chronic illness is crucial because it may enable early laboratory diagnosis, treatment, and significant potential for prevention.^8-12

GUT MICROBIOME AND AUTOIMMUNE DISEASE

The causes of autoimmune disorders (AIDs) involves both genetic predispositions and environmental influences, with a disturbed gut flora garnering more interest. Numerous autoimmune disorders have been linked to functional and compositional alterations in the gut microbiota, and mounting data indicates that disruptions in this area may play a role in the immunopathogenesis of these conditions.⁹

Rheumatoid arthritis

Joint destruction is a symptom of rheumatoid arthritis (RA), it is a systemic autoimmune inflammatory disease. Recent research has shown that a variety of environmental factors, the most significant of which are nutrition, smoking, and infections, play a role in the development of both intestinal/oral dysbiosis and the onset and course of arthritis.^9-11 Patients with RA also exhibit an increased abundance of Prevotella species at the compositional level, including Prevotella copri.^12,13 RA patients have lower levels of Faecal bacterium, a bacterium that is widely acknowledged to be helpful. Furthermore, it was discovered that RA patients had a higher relative abundance of Collinsella.¹⁴ It is interesting to note that severe arthritis is produced when mice sensitive to collagen-induced arthritis (CIA) are vaccinated with Collinsella. Collinsella aerofaciens is thought to be a potential arthritogenic bacterium in the human gut based on in vitro investigations that revealed the bacteria increases gut permeability and stimulates the release of IL-17A, a crucial cytokine involved in the pathogenesis of RA.¹⁴ In conclusion, patients with early RA have a gut microbiota dominated by Prevotella copri and Collinsella, which may have a role in the pathophysiology of the disease.¹⁵ Short-chain fatty acids (SCFAs) have been linked recently to autoimmune arthritis in mice, and it has been shown that SCFAs are crucial for reducing inflammation in RA.^16,17 In RA models, mice lacking SCFA receptors displayed increased inflammation.¹⁸ One of the most prevalent SCFAs, butyrate, has been demonstrated to reduce inflammation in animal models of RA and other inflammatory illnesses. It functions as an endogenous histone deacetylase (HDAC) inhibitor.¹⁹ In mice with CIA, and maybe in patients with RA as well, recent study has demonstrated the importance of intestinal barrier function, particularly for zonulin, peptide that regulates epithelial tight junction permeability.²⁰ Elevated zonulin levels have been linked to inflammation, dysbiosis, and leaky intestinal barrier. Restoring the intestinal barrier in time leading up to development of clinical arthritis may help postpone disease's onset and lessen its severity. This can be achieved using pharmacological treatments like zonulin antagonists/dietary supplements containing SCFA butyrate.

GUT MICROBIOME-GUT INFLAMMATION OR BOWEL DISORDERS

Changes in bowel patterns and pain and discomfort in the abdomen are the main symptoms of syndrome of the irritable bowel (IBS). While the cause of the condition is complex, changes in the normal gut microbiota may contribute to the low-grade intestinal inflammation linked to it, according to new research on the pathophysiology of IBS.³⁰ The pathophysiology of IBS is assumed to be influenced by microbial dysbiosis in the gut. A recent study found a distinct difference in the gut microbiota of IBS patients compared to controls. Firmicutes, notably Ruminococcin, Clostridium, and Dorea, were found in greater abundance in IBS patients, but beneficial bacteria like Bifidobacterium and Faecal bacterium spp were significantly reduced.³¹ Additionally, comprehensive reviews have shown that people with IBS have potentially hazardous microbiota, such as members of the genus Bacteroides (phylum Bacteroidetes), family Lactobacillus, phylum Proteobacteria, and family Enterobacteriaceae. Numerous dangerous bacteria, including Salmonella, Escherichia, Shigella, and Campylobacter, are members of the Enterobacteriaceae family.³² These may indicate a shift in the intestinal environment or a history of intestinal illness in these people. Abdominal pain, bloating, and diarrhoea-three of the characteristic symptoms of IBS-have been linked to buy products from these potentially dangerous bacteria. The uncultured Clostridial group was the most consistently detected potentially "protective" bacterial group in IBS patients. Even though the relationship is not causative and it is unknown how a protective impact on IBS symptoms works. Gut mucosal health has been linked to the genus Faecal bacterium, particularly Faecal bacterium prausnitzii, which shares an order with the uncultured Clostridia. This bacterium was thought to be the primary butyrate-producing and anti-inflammatory organism.³³ It also preserved the integrity of the intestinal barrier and decreased the symptoms of IBS in rats by mediating the expression of IL-17.

Moreover, independent of the IBS subtype, there was a significant decrease in the genus Bifidobacterium in IBS patients. As a result, it was yet another intriguing candidate genus for reducing IBS symptoms. IBS symptoms are reduced by Bifidobacterium-containing therapies, which are not observed in products that include Lactobacillus alone, according to a comprehensive evaluation of probiotics in IBS.³⁴

Restricting fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) can help manage the symptoms of irritable bowel syndrome. The low-FODMAPS diet has been clinically proven to be effective in lowering symptoms of IBS.³⁵ Since FODMAPs can alter microbial composition and microbial metabolite production, one effect of this dietary intervention is on the composition of the gut microbiome.³⁶ Because not every IBS patient responds, and putting a low-FODMAPS diet into practice could be difficult. There has been a growing focus on the potential role of the gut microbiome in predicting the efficacy of the low-FODMAPS diet due to the role of the microbiome in metabolizing poorly absorbed carbohydrates, which depends on an individual's microbiome composition.³⁷ New data suggests that there may be baseline differences in microbiome activity and composition that can distinguish between low-FODMMAP diet responders and non-responders. Inflammatory bowel disease (IBD) is primarily characterized by chronic inflammation and colon ulceration, which are also characteristics of ulcerative colitis (UC) and Crohn's disease (CD). The hallmark of IBD, which includes ulcerative colitis and Crohn's disease, is recurrent, chronic inflammation of the GI tract. It is generally accepted that a widespread microbial dysbiosis in the gut, rather than a particular causative organism, is what causes the beginning of both illnesses.³⁸ Numerous studies have suggested a role for gut microorganisms in the manifestation of IBD, and the gut microbiota is believed to be a crucial component in the formation of mucosal lesions. Previous research has demonstrated changes in the gut microbiota's functionality and composition in individuals with IBD as opposed to those without the disease. A reduction in the microbiota's stability and diversity is a common feature of microbial dysbiosis in IBD.^39,40

In particular, the most consistent finding from IBD microbiome investigations is a rise in Proteobacteria taxa and a decrease in Firmicutes. Additionally, compared to healthy control samples, a typical indicator of microbial dysbiosis in IBD patients, particularly in (active) CD, is the decreased number of Firmicutes bacteria from the families Ruminococcaceae and Lachnospiraceae.⁴¹ Since most butyrate-producing bacteria in the human gut are members of these families, they are significant functional components of the gut microbiota. Thus, the observed disruption on a functional level, such as a reduced ability of the IBD microbiota to produce butyrate, can be associated with the depletion of these bacterial groups in IBD.⁴² Furthermore, a study utilizing metagenomic and proteomics techniques in the ileal CD microbiota revealed a decrease in metagenomic reads and proteins of significant butyrate producers, Faecalibacterium prausnitzii and Roseburia spp., as well as an underrepresentation of genes involved in SCFA generation.⁴³ Because it provides colonocytes with their primary energy source, improves the integrity of the epithelial barrier, and reduces inflammation, butyrate offers therapeutic potential in the treatment of IBD. Consuming bacteria that produce butyrate to boost in situ butyrate production is an alternative probiotic strategy that has been the subject of recent observational and interventional investigations ^[44]. This may imply that addressing microbial dysbiosis using butyrate-producing bacterial supplements could help IBD patients regain gut homeostasis and overall health.

Chronic kidney disease

Research on the makeup of the gut microbiota in CKD patients and the processes by which gut dysbiosis advances the disease are of increasing interest. Both CKD and the gut microbiota have a reciprocal effect on the gut-kidney axis, with the former greatly altering the latter's composition and functioning.⁴⁷ On the other hand, through inflammatory, endocrine, and neurologic pathways, the gut microbiota can influence the processes that lead to the onset and progression of CKD. Therefore, by focusing on the gut microbiota, new therapies to stop the progression of CKD may be made possible by understanding the intricate relationship between these two organs. CKD has been linked to changes in the intestinal microbiota, such as a decrease in microbial richness, variety, and uniformity.⁴⁸ The intestinal levels of Enterobacteriaceae, specifically Enterobacter, Klebsiella, and Escherichia, as well as Enterococci and Clostridium per fringes, are higher in patients with CDK, while the colonization of Bifidobacterium spp., Lactobacillus, Bacteroides, Akkermansia, and Proteaceae genera is lower.^49,50 A changed microbiota in CKD may increase chronic systemic inflammation, as suggested by the negative correlation found between plasma IL-10 levels and the decrease in the abundance of the essential probiotic Akkermansia muciniphilla in CKD patients. The development of chronic systemic inflammation is a significant risk factor for CKD. Dietary fibre consumption is reduced in CDK patients, which is a characteristic that is necessary for the formation of SCFAs. Reduced dietary fibre raises amino nitrogen levels, which the gut microbiota can convert to uremic toxins.⁵¹ An imbalance favouring proteolytic microbiota over fermentative microbiome is characteristic of CDK patients. In addition to having negative consequences, imbalance in favor of proteolytic species is essential to development of CKD. Additionally, it was discovered that patients' serum and feces contained less of the major SCFAs, particularly butyrate, as their CKD progressed.⁵² Nevertheless, more investigation is required to ascertain whether raising circulating SCFA levels might directly help CDK patients' clinical outcomes. Prebiotic, probiotic, and symbiotic supplementation has been found to have positive effects on the gut microbiota-renal axis in several experimental and clinical trials. These have come to light as a possible therapeutic intervention to correct dysbiosis of gut microbiota, lessen oxidative stress/inflammation markers, and regulate gut-derived uremic toxins, like trimethylamine N oxide (TMAO), indoxyl sulphate (IS), and PCS, which have been linked to advancement of CKD.^53-55

MENTAL HEALTH DISORDERS

The "gut-brain axis" refers to the connections between gut microorganisms and neurological functions that have been demonstrated to affect each other.⁵⁸ Three main avenues exist via which the gut microbiota communicates with the brain: the neural pathway (by the vagus nerve and enteric nervous system), the immunological pathway (via cytokines), and the endocrine pathway (via the HPA axis and gut hormones). A compromised state of this relationship may result in the emergence of mental illnesses. Mental health illnesses may be exacerbated by common gut microbial species from the genera Bacteroides and Bifidobacterium, as well as the phylum Firmicutes and Actinobacteria.⁵⁹ The gut-brain axis is modulated by gut microbiota in a variety of direct and indirect ways. This includes generating a wide range of metabolites, such as neurotransmitters, SCFAs, and amino acids, and preserving gut permeability by adjusting the integrity of tight junctions in the gut epithelium. These metabolites from the gut can enter circulation and impact the brain, or they can operate locally on the enteric nervous system to affect the central nervous system. Additionally, changes in the levels of gut microbial metabolites, including tryptophan, histamine, ammonia, and SCFAs, have been linked to several neurological conditions, including Parkinson's disease (PD), anorexia nervosa (AN), Alzheimer's disease (AD), autism spectrum disorder (ASD), and chronic stress and depression.^60-62 These relationships may be direct or indirect. More research is necessary to determine if the breakdown of homeostasis in mental health disorders is the result of or the cause of changes in the gut microbiota and its functions.

Considering the available data, numerous investigations have been conducted to precisely target the gut microbiota using various therapeutic approaches, such as the administration of pre- and probiotics (psych biotics) to treat mental health conditions and their symptoms.^63,64 Probiotic combinations of lactobacilli and Bifidobacteria have been shown in human-intervention studies with psychotics to significantly reduce psychological distress.⁶⁵ improve communication and cognition in patients with ASD and AD. and alleviate symptoms in patients with PD.⁶⁶

CONCLUSION

The gut microbiota and CDs, such as inflammatory autoimmune disorders, gut inflammation-related disorders, and cardiometabolic diseases, have been clearly linked in the last ten years of research involving both human and animal investigations. It is becoming more and more evident that bacterial metabolites play a major role in the impact of the gut microbiome on human health, at least in part. Of these metabolites, SCFAs seem to be the most significant. Bacteria that produce butyrate have been linked to a decreased risk of irritable bowel syndrome, inflammatory autoimmune diseases, and cardiometabolic disorders.

Although there are several potential treatment approaches that target the gut microbiome, dietary modifications seem to be the most obvious, quick, non-invasive strategy to modify the makeup and function of the gut microbiome. Recent RCTs have demonstrated that certain dietary treatments have a consistent effect on both composition and function. When dietary fibre and unsaturated fat are consumed together or in a balanced diet like the Mediterranean diet, butyrate-producing bacteria are found in larger relative abundances. The resulting SCFAs and these bacteria lead to better health outcomes. distinct dietary fibre kinds cause distinct bacterial alterations and SCFAs. Within the next five years, it should be possible to create dietary interventions that are particularly aimed at raising specific bacterial metabolites to enhance the outcomes related to inflammation, metabolism, and cardiovascular health.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

REFERENCES

1. 1. Hajat C, Stein E. The global burden of multiple chronic conditions: A narrative review. Prev Med Rep. 2018;12:284-93.
2. 2. Center for Disease Control and Prevention. Chronic diseases in America. Available at: https://www.cdc.gov/chronic-disease/index.html. Accessed on 12 April 2024.
3. 3. Bernell S, Howard SW. Use your words carefully: what is a chronic disease? Front Public Health. 2016;4:159.
4. 4. Medicinenet. Available at: https://www.medicinenet.com/. Accessed on 12 April 2024.
5. 5. Wikipedia. Chronic condition. Available at: https://en.wikipedia.org/wiki/Chronic_condition. Accessed on 12 April 2024.
6. 6. Murphy SL Xu J, Kochanek KD. Deaths: final data for 2010. Natl Vital Stat Rep. 2013;61(4):1-118.
7. 7. Joshi R, Khandelwal B, Joshi D, Gupta OP. Chlamydophila pneumoniae infection and cardiovascular disease. N. Am. J. Med. Sci. 2013;5:169-81.
8. 8. O’Connor SM, Taylor CE, Hughes JM. Emerging infectious determinants of chronic diseases. Emerg Infect Dis. 2006;12:1051-57.
9. 9. de Oliveira GLV, Leite AZ, Higuchi BS, Gonzaga MI, Mariano VS. Intestinal dysbiosis and probiotic applications in autoimmune diseases. Immunology. 2017;152:1-12.
10. 10. Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife. 2013;2:e01202.
11. 11. Wells PM, Adebayo AS, Bowyer RCE, Freidin MB, Finckh A, Strowig T, et al. Associations between gut microbiota and genetic risk for rheumatoid arthritis in a cross-sectional study. Lancet Rheumatol. 2020;2(7):e418-27.
12. 12. Donohoe DR, Wali A, Brylawski BP, Bultman SJ. Microbial regulation of glucose metabolism and cell-cycle progression in mammalian colonocytes. PLoS One. 2012;7(9):e46589.
13. 13. Alpizar-Rodriguez D, Lesker TR, Gronow A, Gilbert B, Raemy E, Lamacchia C, et al. Prevotella copri in individuals at risk for rheumatoid arthritis. Ann Rheum Dis. 2019;78(5):590-3.
14. 14. Chen J, Wright K, Davis JM, Jeraldo P, Marietta EV, Murray J, et al. An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis. Genome Med. 2016;8(1):43.
15. 15. Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med. 2015;21(8):895-905.
16. 16. Chen Z, Andreev D, Oeser K, Krljanac B, Hueber A, Kleyer A, et al. Th2 and eosinophil responses suppress inflammatory arthritis. Nat Commun. 2016;7:11596.
17. 17. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461(7268):1282-6.
18. 18. Wang L, de Zoeten EF, Greene MI, Hancock WW. Immunomodulatory effects of deacetylase inhibitors: therapeutic targeting of FOXP3+ regulatory T cells. Nat Rev Drug Disco. 2009;8(12):969-81.
19. 19. Tajik N, Frech M, Schulz O, Schälter F, Lucas S, Azizov V, et al. Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis. Nat Commun. 2020;11(1):1995.
20. 20. Kostic AD, Gevers D, Siljander H, Vatanen T, Hyötyläinen T, Hämäläinen A-M, et al. The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe. 2015;17(2):260-73.
21. 21. De Goffau MC, Fuentes S, van den Bogert B, Honkanen H, de Vos WM, Welling GW, et al. Aberrant gut microbiota composition at the onset of type 1 diabetes in young children. Diabetologia. 2014;57(8):1569-77.
22. 22. Mariño E, Richards JL, McLeod KH, Stanley D, Yap YA, Knight J, et al. Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes. Nat Immunol. 2017;18(5):552-62.
23. 23. Kirjavainen PV, Arvola T, Salminen SJ, Isolauri E. Aberrant composition of gut microbiota of allergic infants: a target of bifidobacterial therapy at weaning? Gut. 2002;51(1):51-5.
24. 24. Song H, Yoo Y, Hwang J, Na Y-C, Kim HS. Faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis. J Allergy Clin Immunol. 2016;137(3):852-60.
25. 25. Barcik W, Boutin RCT, Sokolowska M, Finlay BB. The role of lung and gut microbiota in the pathology of asthma. Immunity. 2020;52(2):241-55.
26. 26. Chu DM, Ma J, Prince AL, Antony KM, Seferovic MD, Aagaard KM. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat Med. 2017;23(3):314-26.
27. 27. Korpela K, Salonen A, Virta LJ, Kekkonen RA, Forslund K, Bork P, et al. Intestinal microbiome is related to lifetime antibiotic use in finnish pre-school children. Nat Commun. 2016;7:10410.
28. 28. Levin AM, Sitarik AR, Havstad SL, Fujimura KE, Wegienka G, Cassidy-Bushrow AE, et al. Joint effects of pregnancy, sociocultural, and environmental factors on early life gut microbiome structure and diversity. Sci Rep. 2016;6:31775.
29. 29. Lopez-Siles M, Duncan SH, Garcia-Gil LJ, Martinez-Medina M. Faecalibacterium prausnitzii: from microbiology to diagnostics and prognostics. ISME J. 2017;11(4):841-52.
30. 30. Wang H, Gong J, Wang W, Long Y, Fu X, Fu Y, et al. Are there any different effects of bifidobacterium, lactobacillus and streptococcus on intestinal sensation, barrier function and intestinal immunity in PI-IBS mouse model? PLoS One. 2014;9(3):e90153.
31. 31. Vijay A, Valdes AM. Role of the gut microbiome in chronic diseases: a narrative review. Eur J Clin Nutrit. 2022;76(4):489-501.
32. 32. Ford AC, Harris LA, Lacy BE, Quigley EMM, Moayyedi P. Systematic review with meta-analysis: the efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndrome. Aliment Pharm Ther. 2018;48(10):1044-60.
33. 33. Kostic AD, Xavier RJ, Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology. 2014;146(6):1489-99.
34. 34. Ott SJ, Musfeldt M, Wenderoth DF, Hampe J, Brant O, Fölsch UR, et al. Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut. 2004;53(5):685-93.
35. 35. Walker AW, Sanderson JD, Churcher C, Parkes GC, Hudspith BN, Rayment N, et al. High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease. BMC Microbiol. 2011;11:7.
36. 36. Tong M, Li X, Wegener Parfrey L, Roth B, Ippoliti A, Wei B, et al. A modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel disease. PLoS One. 2013;8(11):e80702.
37. 37. Martinez C, Antolin M, Santos J, Torrejon A, Casellas F, Borruel N, et al. Unstable composition of the fecal microbiota in ulcerative colitis during clinical remission. Am J Gastroenterol. 2008;103(3):643-8.
38. 38. Matsuoka K, Kanai T. The gut microbiota and inflammatory bowel disease. Semin Immunopathol. 2015;37(1):47-55.
39. 39. Halfvarson J, Brislawn CJ, Lamendella R, Vázquez-Baeza Y, Walters WA, Bramer LM, et al. Dynamics of the human gut microbiome in inflammatory bowel disease. Nat Microbiol. 2017;2:17004.
40. 40. Mottawea W, Chiang C-K, Mühlbauer M, Starr AE, Butcher J, Abujamel T, et al. Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn’s disease. Nat Commun. 2016;7:13419.
41. 41. Van Immerseel F, Ducatelle R, De Vos M, Boon N, Van De Wiele T, Verbeke K, et al. Butyric acid-producing anaerobic bacteria as a novel probiotic treatment approach for inflammatory bowel disease. J Med Microbiol. 2010;59(pt2):141-3.
42. 42. Lam V, Su J, Koprowski S, Hsu A, Tweddell JS, Rafiee P, et al. Intestinal microbiota determine severity of myocardial infarction in rats. FASEB J. 2012;26(4):1727-35.
43. 43. Lam V, Su J, Hsu A, Gross GJ, Salzman NH, Baker JE. Intestinal microbial metabolites are linked to severity of myocardial infarction in rats. PLoS One. 2016;11(8):e0160840.
44. 44. Jackson MA, Verdi S, Maxan M-E, Shin CM, Zierer J, Bowyer RCE, et al. Gut microbiota associations with common diseases and prescription medications in a population-based cohort. Nat Commun. 2018;9(1):2655.
45. 45. Chumpitazi BP. The gut microbiome as a predictor of low fermentable oligosaccharides disaccharides monosaccharides and polyols diet efficacy in functional bowel disorders. Curr Opin Gastroenterol. 2020;36(2):147-54.
46. 46. Walker AW, Sanderson JD, Churcher C, Parkes GC, Hudspith BN, Rayment N, et al. High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease. BMC Microbiol. 2011;11:7.
47. 47. Larsen N, Vogensen FK, van den Berg FWJ, Nielsen DS, Andreasen AS, Pedersen BK, et al. Gut microbiota in human adults with type 2 diabetes differs from nondiabetic adults. PLoS One. 2010;5(2):e9085.
48. 48. Mafra D, Borges N, Alvarenga L, Esgalhado M, Cardozo L, Lindholm B, et al. Dietary components that may influence the disturbed gut microbiota in chronic kidney disease. Nutrients. 2019;11(3):496.
49. 49. Tayebi-Khosroshahi H, Habibzadeh A, Niknafs B, Ghotaslou R, Yeganeh Sefidan F, Ghojazadeh M, et al. The effect of lactulose supplementation on fecal microflora of patients with chronic kidney disease; a randomized clinical trial. J Ren Inj Prev. 2016;5(3):162-7.
50. 50. Wanchai K, Yasom S, Tunapong W, Chunchai T, Thiennimitr P, Chaiyasut C, et al. Prebiotic prevents impaired kidney and renal Oat3 functions in obese rats. J Endocrinol. 2018;237(1):29-42.
51. 51. Mayer EA, Tillisch K, Gupta A. Gut/brain axis and the microbiota. J Clin Invest. 2015;125(3):926-38.
52. 52. Maldonado-Contreras A, Noel SE, Ward DV, Velez M, Mangano KM. Associations between diet, the gut microbiome, and short-chain fatty acid production among older Caribbean Latino adults. J Acad Nutr Diet. 2020;120(12):2047.e6.
53. 53. Prehn-Kristensen A, Zimmermann A, Tittmann L, Lieb W, Schreiber S, Baving L, et al. Reduced microbiome alpha diversity in young patients with ADHD. PLoS One. 2018;13(7):e0200728.
54. 54. Caspani G, Kennedy S, Foster JA, Swann J. Gut microbial metabolites in depression: understanding the biochemical mechanisms. Micro Cell Fact. 2019;6(10):454-81.
55. 55. Roubalová R, Procházková P, Papežová H, Smitka K, Bilej M, Tlaskalová-Hogenová H. Anorexia nervosa: gut microbiota-immune-brain interactions. Clin Nutr. 2020;39(3):676-84.
56. 56. van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl J Med. 2013;368(5):407-15.
57. 57. Colman RJ, Rubin DT. Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis. 2014;8(12):1569-81.
58. 58. Zhang L, Wang Y, Xiayu X, Shi C, Chen W, Song N, et al. Altered gut microbiota in a mouse model of Alzheimer’s disease. J Alzheimers Dis. 2017;60(4):1241-57.
59. 59. Wang L, Christophersen CT, Sorich MJ, Gerber JP, Angley MT, Conlon MA. Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder. Dig Dis Sci. 2012;57(8):2096-102.
60. 60. Galland L. The gut microbiome and the brain. J Med Food. 2014;17(12):1261-72.
61. 61. Barbosa RSD, Vieira-Coelho MA. Probiotics and prebiotics: focus on psychiatric disorders-a systematic review. Nutr Rev. 2020;78(6):437-50.
62. 62. Ansari F, Pourjafar H, Tabrizi A, Homayouni A. The effects of probiotics and prebiotics on mental disorders: a review on depression, anxiety, Alzheimer, and autism spectrum disorders. Curr Pharm Biotechnol. 2020;21(7):555-65.
63. 63. Yeoh YK, Zuo T, Lui GC-Y, Zhang F, Liu Q, Li AY, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021;70(4):698-706.
64. 64. Zmora N, Zilberman-Schapira G, Suez J, Mor U, Dori-Bachash M, Bashiardes S, et al. Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell. 2018;174:1388-1405.e21.
65. 65. Abraham B, Quigley EMM. Antibiotics and probiotics in inflammatory bowel disease: when to use them? Frontline Gastroenterol. 2020;11(1):62-9.
66. 66. Deehan EC, Yang C, Perez-Muñoz ME, Nguyen NK, Cheng CC, Triador L, et al. Precision microbiome modulation with discrete dietary fiber structures directs short-chain fatty acid production. Cell Host Microbe. 2020;27(3):389-404.e6.
67. 67. Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500(7564):585-8.
68. 68. Pereira MA, O’Reilly E, Augustsson K, Fraser GE, Goldbourt U, Heitmann BL, et al. Dietary fiber and risk of coronary heart disease: a pooled analysis of cohort studies. Arch Intern Med. 2004;164(4):370-6.
69. 69. Berry SE, Valdes AM, Drew DA, Asnicar F, Mazidi M, Wolf J, et al. Human postprandial responses to food and potential for precision nutrition. Nat Med. 2020;26(6):964-73.
70. 70. Zeevi D, Korem T, Zmora N, Israeli D, Rothschild D, Weinberger A, et al. Personalized nutrition by prediction of glycemic responses. Cell. 2015;163(5):1079-94.
71. 71. Asnicar F, Berry SE, Valdes AM, Nguyen LH, Piccinno G, Drew DA, et al. Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals. Nat Med. 2021;27(2):321-32.
72. 72. Gurung M, Li Z, You H, Rodrigues R, Jump DB, Morgun A, et al. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine. 2020;51:102590.
73. 73. Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490(7418):55-60.
74. 74. Vrieze A, Out C, Fuentes S, Jonker L, Reuling I, Kootte RS, et al. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. J Hepatol. 2014;60(4):824-31.