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intestinal bacteria (flora)

Bacteria present in the intestinal tract. Also see normal microbial flora. Classification: - enterotypes [31] - Bacteroides enterotype (B-type) - Ruminococcaceae enterotype (R-type) - Prevotella enterotype (P-type) * B-type with lower stool energy density, shorter intestinal transit times, & lower alpha-diversity compared to R-type * P-type intermediate between B-type & R-type [31] * B-type individuals heavier than R-type Physiology: - small intestine - Lactobacillus spp (3+) - Bacteroides spp (3+) - Clostridium spp (2+) - Mycobacterium spp (2+) - Enterococci (2+) - Enterobacteriaceae (2+) - large intestine - Bacteroides spp (4+) - Fusobacterium spp - Fusobacterium nucleatum may be increased in patients with colon cancer - Ruminococcaceae - Ruminococcus (neuroprotective) - Butyricicoccus (neuroprotective) - Clostridium spp (4+) - Peptostreptococcus spp (4+) - Enterobacteriaceae (4+) - Escherichia coli - Klebsiella spp - Proteus spp - Lactobacillus spp (3+) - Enterococci (2+) - Streptococci - Pseudomonas spp (1+) - Acinetobacter spp - coagulase-negative staphylococci (1+) - Staphylococcus aureus (1+) - Mycobacterium spp (1+) - Actinomyces spp * the adherens junctions of the intestinal epithelium provide a barrier to the movement of intestinal bacteria from the gut lumen into tissues & the circulation * exercise increases diversity of gut microbiota [9,19] - diet also plays a role [9] * antibiotic or probiotic use affects gut microbiota [19] * fecal transplantation alters gut microbiota [19] * > 400 species [10] * estimated weight of microbial flora in human gut is 1-1.4 kg * an infant's intestinal flora is strongly influenced by the mother's intestinal flora during vaginal delivery * in life a person's intestinal flora is influenced by diet & lifestyle * gut microbiota similiar in health aged & health young Chinese [16] Epidemiology: - men who have sex with men have Prevotella-dominant microbiomes - Prevotella-dominant microbiome associated with HIV1 infection - other men have Bacteroides-dominant microbiomes [8] - Veillonella atypica found in higher concentrations in intestines of marathon runners than in nonathletes [26] - in middle-age subjects intestinal bacteria were associated with cognitive effects - Barnesiella with benefit in cognitive testing including - digital symbol substitution test - category fluency - Lachnospiraceae FCS020 group with benefit on digital symbol substitution test - Sutterella with poorer performance on Montreal Cognitive Assessment [29] Pathology: - intestinal flora appear to be implicated in obesity, dyslipidemia, & insulin resistance [2] - oral antibiotics reduce microbiome diversity in feces [5] - specifically, bacteria that produce butyrate* are reduced - clindamycin reduces microbiome diversity for up to 4 months - ciprofloxacin reduces microbiome diversity for up to 12 months - 24% of non-antibiotic drugs, members of all therapeutic classes, inhibit growth of at least one intestinal strain in vitro [22] - antipsychotics, other psychoactive agents, proton-pump inhibitors, antineoplastics, & hormones over-represented [22] - bacteria resistant to various antibiotics also were resistant to inhibiting effects of nonantibiotics [22] - bacterial mutations that eject antibiotics from bacterial cells also ejected some nonantibiotic drugs [22] - animal-based diets increase the abundance of bile-tolerant microorganisms (Alistipes, Bilophila, Bacteroides) - activity of Bilophila wadsworthia associated with an animal-based diet may play a role in triggering inflammatory bowel disease [3] - plant-based diets increase the abundance of Firmicutes (Roseburia, Eubacterium rectale, Ruminococcus bromii) that metabolize dietary plant polysaccharides [3] - Fusobacterium nucleatum appears to be implicated in colorectal carcinoma - Bacteroides species present in intestinal flora of infants may suppress development of tolerance to self-antigens & increase risk of type 1 diabetes [11] - gut microbial viversity diminishes with increased frailty in community-dwelling elderly & in long-term care residents [13] - intestinal bacteria of the Ruminococcaceae family & Clostridiales order, & especially of the genus Faecalibacterium confer better response to anti-PD-1 immunotherapy in patients with melanoma [17] - intestinal bacteria of the Bacteroidales order confer worse response to anti-PD-1 immunotherapy [17] - responders to immunotherapy for metastatic melanoma with gut microbiome abundant in 8 bacterial species [19] - recent antibiotics confer worse response in patients with lung cancer, renal cell carcinoma, & urothelial cancer undergoing anti-PD-1 immunotherapy [17] - abundance of Akkermansia muciniphila associated with the best clinical outcomes [17] - dietary salt decreases intestinal Lactobacilli in mice & humans & increases blood pressure [18] - elevated levels of phenylacetylglutamine, a byproduct of microbial break down dietary protein, increases risk of heart failure & severity, & risk of myocardial infarction, stroke & death [30] - Enterococcus gallinarum may be associated with lupus [21] - the microbiome may influence development of both obesity & type 2 diabetes,1 both of which are atherogenic [23] - intestinal bacteria produce neuroactive molecules as well as molecules that influence cells to produce neuroactive agents [24] - metabolism of intestinal bacteria appear to be linked to functional status & mood, possibly influencing depression [24] - 47 specific bacterial species, 3 specific bacteriophages, & 50 fecal metabolites are significantly associated with major depression [27] - among the 50 metabolites gamma-aminobutyrate, phenylalanine & tryptophan enter the blood from the gut, affect neurochemistry, & have been implicated in major depression [27] * butyrate-producing bacteria are linked to lower inflammation, carcinogenesis, & oxidative stress in the gut [5] Genetics: - for some bacteria, i.e. Bacteroidetes, environmental influences are much greater than genomic influences [4] - for bacteria, i.e. Christensenellaceae, the opposite was true - Christensenellaceae appear to protect against obesity [4] Pharmacology: - some bacteria can store a drug without chemically modifying it - other bacteria chemically modify it to make it more or less bioactive - a drug can affect a patient's gut bacteria, their number & function - accumulation of a drug within a strain of bacteria can alter the growth rate of those bacteria - a drug can change molecules secreted by bacteria, including hormones, neurotransmitters, & inflammatory molecules [28] - communities of intestinal bacteria influence response to checkpoint inhibitors in patients with non-small cell lung carcinoma [35] Comparative biology: - nonpathogenic Clostridia (17 strains) normally found in human intestinal flora can suppress immunologically mediated disease in mice - the Clostridial strains induce CD4+FOXP3+ regulatory T-cells - promise for treatment of inflammation & allergy - fecal transplantation from mice with anti-melanoma immunity augments responses to anti-PDL1 immunotherapy [6] - augmented response apparently conferred by Bifidobacterium - probiotic therapy with Bifidobacterium species prevented or ameliorated autoimmune colitis in a mouse melanoma model [20] - effect mediated by regulatory T cells (CTLA4 inhibition) [20] - fecal transplantation into mice from patients treated with ipilimumab enhances responses of mice to anti-CTLA4 therapy [7] - high-glycemic index diets worsen macular deneration in mice - low glycemic index diets arrest progession of macular deneration in mice - changes dependent on changes in the gut microbiome [14] - lipopolysaccharide (LPS) produced by gram-negative bacteria can penetrate the gut mucosa during inflammation & can enter the circulation in mice [15] - LPS stimulates TKR4 on the endothelial wall of cerebral blood vessels & this triggers morphologic changes that evolve into serebral cavernous malformations, strokes & seizures [15] - Enterococcus gallinarum can penetrate intestinal epithelium, translocate to mesenteric lymph nodes & liver, resulting in condition similar to systemic lupus erythematosus in mice [21] - prebiotic (10% oligofructose-enriched inulin) fed to mice altered gut microbiota in young & middle-aged mice with changes correlating with fecal metabolites; Functionally, this translated into a reversal of stress-induced immune priming in middle-aged mice, reduction of infiltration of monocytes inro brain & a reversal in ageing-related increases in a subset of activated microglia [25] - microbiome-dependent production of endocannabinoid metabolites in the gut stimulates activity of TRPV1-expressing sensory neurons thus elevating dopamine levels in the ventral striatum during exercise in mice [32] - this increases the desire of mice to exercise [32] - in 3xTg-AD mice, Klebsiella pneumoniae can translocate from the gut to the bloodstream by penetrating the gut epithelial barrier & susequently infiltrate the brain by penetrating the blood-brain barrier [36] Notes: - Lactobacillus rhamnosus GG strain may benefit memory [33] - Prevotella may negatively impact memory [33] - for resistant isolates of enteric bacteria, report to EntericBacteria@cdc.gov

Related

intestinal epithelium small intestinal bacterial overgrowth

General

bacteria intestinal flora; gut microbiome

References

  1. Atarashi K, Tanoue T, Oshima K et al Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. 2013 Aug 8;500(7461):232-6 PMID: 23842501
  2. Ridaura VK et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 2013 Sep 6; 341:1079 PMID: 24009397 http://www.sciencemag.org/content/341/6150/1241214 - Le Chatelier E et al. Richness of human gut microbiome correlates with metabolic markers. Nature 2013 Aug 29; 500:541. PMID: 23985870 - Cotillard A et al. Dietary intervention impact on gut microbial gene richness. Nature 2013 Aug 29; 500:585 PMID: 2398587
  3. David LA et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014 Jan 23; 505:559 PMID: 24336217 http://www.nature.com/nature/journal/v505/n7484/full/nature12820.html
  4. Goodrich JK et al. Human genetics shape the gut microbiome. Cell 2014 Nov 6; 159:789 PMID: 25417156
  5. Zaura E et al Same Exposure but Two Radically Different Responses to Antibiotics: Resilience of the Salivary Microbiome versus Long-Term Microbial Shifts in Feces. mBio Nov 10, 2015 PMID: 26556275 http://mbio.asm.org/content/6/6/e01693-15.full
  6. Sivan A, Corrales L, Hubert N et al Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015 Nov 27;350(6264):1084-9 PMID: 26541606
  7. Vetizou M, Pitt JM, Daillere R et al Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015 Nov 27;350(6264):1079-84 PMID: 26541610
  8. Noguera-Julian M et al. Gut microbiota linked to sexual preference and HIV infection. EBioMedicine 2016 Mar; 5:135 PMID: 27077120 Free PMC Article http://www.ebiomedicine.com/article/S2352-3964%2816%2930028-7/abstract
  9. Clarke SF et al Exercise and associated dietary extremes impact on gut microbial diversity. Gut. June 9, 2014 PMID: 25021423 http://gut.bmj.com/content/early/2014/04/29/gutjnl-2013-306541 - Hold GL The gut microbiota, dietary extremes and exercise. Gut. June 9, 2014 PMID: 25021422 http://gut.bmj.com/content/early/2014/05/28/gutjnl-2014-307305.extract
  10. Kraehenbuhl JP & Corbett M, Immunology. Keeping the gut microflora at bay. Science 303, 1624, 2004 PMID: 15016988
  11. Vatanen T, Kostic AD, d'Hennezel E et al. Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans. Cell 2016 May 5; 165:842. PMID: 27259157
  12. Lynch SV, Pedersen O The Human Intestinal Microbiome in Health and Disease. N Engl J Med 2016; 375:2369-2379. December 15, 2016 PMID: 27974040 http://www.nejm.org/doi/full/10.1056/NEJMra1600266
  13. Claesson MJ, Jeffery IB, Conde S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature 2012;488:178-184 PMID: 22797518
  14. Rowan S, Jiang S, Korem T et al. Involvement of a gut-retina axis in protection against dietary glycemia-induced age-related macular degeneration. Proc Natl Acad Sci U S A 2017 May 15; http://www.pnas.org/content/early/2017/05/09/1702302114
  15. Tang AT, Choi JP, Kotzin JJ et al. Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. Nature 2017 May 18; 545:305. PMID: 28489816 https://www.nature.com/nature/journal/v545/n7654/full/nature22075.html
  16. Bian G, Gloor GB, Gong A et al The Gut Microbiota of Healthy Aged Chinese Is Similar to That of the Healthy Young. mSphere. 2017 Oct PMID: 28959739 Free PMC Article http://msphere.asm.org/content/2/5/e00327-17
  17. Minerd J. Does Gut Flora Impact the Response to Cancer Immunotherapy? Modulating the microbiome could boost therapy, studies suggest. MedPage Today. November 07, 2017 https://www.medpagetoday.com/hematologyoncology/myeloma/69098 - Gopalakrishnan V, Spencer CN, Nezi L et al Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2017 Nov 2. PMID: 29097493 - Routy B, Le Chatelier E, Derosa L et al Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2017 Nov 2. PMID: 29097494
  18. Wilck N, Matus MG, Kearney SM et al. Salt-responsive gut commensal modulates TH17 axis and disease. Nature 2017 Nov 30; 551:585. PMID: 29143823 https://www.nature.com/articles/nature24628 - Relman DA. Microbiota: A high-pressure situation for bacteria. Nature 2017 Nov 30; 551:571 PMID: 29143820 https://www.nature.com/articles/nature24760
  19. Castellino AM Manipulating Gut Microbiome to Improve Immunotherapy Response. Medscape - Jan 10, 2018. https://www.medscape.com/viewarticle/891152 - Jobin C Precision medicine using microbiota. Science 2018 359(6371):32-34. Jan 5 2018: PMID: 29302001 http://science.sciencemag.org/content/359/6371/32
  20. Wang F, Yin Q, Chen L, Davis MM. Bifidobacterium can mitigate intestinal immunopathology in the context of CTLA-4 blockade. Proc Natl Acad Sci U S A 2018 Jan 2; 115:157 PMID: 29255057 http://www.pnas.org/content/115/1/157
  21. Mohanan V, Nakata T, Desch AN et al. Clorf106 is a colitis risk gene that regulates stability of epithelial adherens junctions. Science 2018 Mar 9; 359:1161. PMID: 29420262 - Manfredo Vieira S, Hiltensperger M, Kumar V et al. Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science 2018 Mar 9; 359:1156. PMID: 29590047 - Thaiss CA, Levy M, Grosheva I et al. Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection. Science 2018 Mar 23; 359:1376. PMID: 29519916 - Citi S et al. Intestinal barriers protect against disease. Science 2018 Mar 9; 359:1097 PMID: 29590026
  22. Maier L, Pruteanu M, Kuhn M et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 2018 Mar 29; 555:623. PMID: 29555994 https://www.nature.com/articles/nature25979
  23. Komaroff AL The Microbiome and Risk for Atherosclerosis JAMA. Published online May 14, 2018 PMID: 29800043 https://jamanetwork.com/journals/jama/fullarticle/2681622
  24. Valles-Colomer M, Falony G, Darzi Y et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol 2019 Feb 4; PMID: 30718848 https://www.nature.com/articles/s41564-018-0337-x
  25. Boehme M, van de Wouw M, Bastiaanssen TFS et al Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome. Mol Psychiatry. 2019 May 16. PMID: 31092898
  26. Scheiman J, Luber JM, Chavkin TA et al. Meta-omics analysis of elite athletes identifies a performance- enhancing microbe that functions via lactate metabolism. Nat Med 2019 Jul; 25:1104. PMID: 31235964 https://www.nature.com/articles/s41591-019-0485-4
  27. Yang J, Zheng P, Li Y et al. Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders. Sci Adv 2020 Dec 2; 6:eaba8555 PMID: 33268363 PMCID: PMC7710361 Free PMC article https://advances.sciencemag.org/content/6/49/eaba8555
  28. Klunemann M, Andrejev S, Blasche S et al. Bioaccumulation of therapeutic drugs by human gut bacteria. Nature 2021 Sep; 597:533 PMID: 34497420 https://www.nature.com/articles/s41586-021-03891-8
  29. Meyer K, Lulla A, Debroy K et al Association of the Gut Microbiota With Cognitive Function in Midlife. JAMA Netw Open. 2022;5(2):e2143941. PMID: 35133436 PMCID: PMC8826173 Free PMC article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788843
  30. Hughes S Product of Gut Microbiome Implicated in Heart Failure Risk. Medscape. Dec 22, 2022 https://www.medscape.com/viewarticle/986052 - Romano KA, Nemet I, Saha PP et al Gut Microbiota-Generated Phenylacetylglutamine and Heart Failure. Circulation: Heart Failure. 2022. Dec 16. PMID: 36524472 https://www.ahajournals.org/doi/abs/10.1161/CIRCHEARTFAILURE.122.009972
  31. Boekhorst J, Venlet N, Prochazkova N et al Stool energy density is positively correlated to intestinal transit time and related to microbial enterotypes. Microbiome 2022. 10:223. Dec 12 PMID: 36510309 PMCID: PMC9743556 Free PMC article https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-022-01418-5
  32. Watkins D Science Reveals Link Between Gut Health and Exercise Motivation. Medscape. January 05, 2023 https://www.medscape.com/viewarticle/986535 - Dohnalova L, Lundgren P, Carty JRE et al A microbiome-dependent gut - brain pathway regulates motivation for exercise. Nature. 2022 Dec;612(7941):739-747. PMID: 36517598 https://www.nature.com/articles/s41586-022-05525-z.epdf
  33. Fauzia M A Common Probiotic Could Boost Brain Health in Older Adults. https://www.msn.com/en-us/health/medical/a-common-probiotic-could-boost-brain-health-in-older-adults/ar-AA1ehttK
  34. Singh S, Giron LB, Shaikh MW et al. Distinct intestinal microbial signatures linked to accelerated systemic and intestinal biological aging. Microbiome. 2024 Feb 22;12(1):31. doi: 10.1186/s40168-024-01758-4. PMID: 38383483 PMCID: PMC10882811 Free PMC article.
  35. Guglielmi G Gut microbiome discovery provides roadmap for life-saving cancer therapies. The balance between bacterial communities in the gut affects the likelihood of a positive response to drugs called checkpoint inhibitors. Nature News. June 24, 2024 https://www.nature.com/articles/d41586-024-02070-9 - Derosa L, Iebba V, Silva CAC et al. Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome. Cell. 2024. Jun 20;187(13):3373-3389.e16 PMID: 38906102 Free article. https://www.cell.com/cell/fulltext/S0092-8674(24)00538-5
  36. Park G, Kadyan S, Hochuli N et al An Enteric Bacterial Infection Triggers Neuroinflammation and Neurobehavioral Impairment in 3xTg-AD Transgenic Mice. J Infect Dis. 2024 Sep 10;230(Supplement_2):S95-S108. PMID: 39255397

Component-of

microbial flora (microbiome)