Skip to main content

Mesenteric Microbiology and Inflammatory Bowel Disease: Improved Understanding Due to Accelerating Innovation and Sophistication of Molecular Technology

  • Chapter
  • First Online:
The Mesentery and Inflammation

Abstract

It is incontrovertible that relationships exist between the intestinal microbiome and intestinal structure, function, health and disease. Understanding these relationships has been enabled through the evolution of microbiology techniques; from growth and enumeration using media selective for specific species to current exploitation of technologies that allow insight regarding the dialogue between complex microbial communities and host responses. In the context of inflammatory bowel disease, most initial microbiology studies involved analysis of stool or excreted mucus samples, in essence reflective of luminal contents transiting the intestinal environment. Endoscopy, biopsies and availability of resected intestinal tissues further enhanced the analysis. However, the majority of studies were observational and, in many cases, attempted to determine cause or effect interactions between predetermined species, mainly bacteria, inflammation or beneficial/probiotic characteristics. Exceptions to this approach included use of denaturing gradient or temperature gradient electrophoresis and shotgun sequencing approaches that facilitated characterisation of subsets of microbial communities. Notably, these advances explored the intestinal mesentery rarely and, when performed, investigations concentrated on adipose components and, as with prior studies on luminal contents or mucus-adhering microflora, failed to determine whether the presence of bacteria was due to passive or active translocation processes or whether detected microbial profiles were unambiguously characteristic of either Crohn’s disease (CD) or ulcerative colitis (UC). We have employed next-generation sequencing of bacteria from mesenteric lymph nodes of IBD patients to clarify these questions somewhat by differentiating CD and UC unequivocally. We have also employed more sophisticated techniques to elucidate the metagenome of mesenteric lymph nodes and confirmed that the bacterial profiles of CD and UC are discrete and distinctive. Further, we have explored emerging data regarding metagenomic innovations and believe that these bacterial signatures, perhaps combined with complementary assays of systemic biomarkers, may allow resolution of the issue of unclassified IBD (IBDU) and selection of optimal therapeutic and/or surgical approaches.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Coffey JC, Sehgal R, Culligan K, Dunne C, McGrath D, Lawes N, et al. Terminology and nomenclature in colonic surgery: universal application of a rule-based approach derived from updates on mesenteric anatomy. Tech Coloproctol. 2014;18(9):789–94. https://doi.org/10.1007/s10151-014-1184-2.

    Article  CAS  Google Scholar 

  2. Coffey JC, Culligan K, Walsh LG, Sehgal R, Dunne C, McGrath D, et al. An appraisal of the computed axial tomographic appearance of the human mesentery based on mesenteric contiguity from the duodenojejunal flexure to the mesorectal level. Eur Radiol. 2016;26(3):714–21. https://doi.org/10.1007/s00330-015-3883-0.

    Article  Google Scholar 

  3. Coffey JC, O’Leary DP. The mesentery: structure, function, and role in disease. Lancet Gastroenterol Hepatol. 2016;1(3):238–47. https://doi.org/10.1016/S2468-1253(16)30026-7.

    Article  Google Scholar 

  4. Coffey JC, O’Leary DP. Defining the mesentery as an organ and what this means for understanding its roles in digestive disorders. Expert Rev Gastroenterol Hepatol. 2017;11(8):703–5. https://doi.org/10.1080/17474124.2017.1329010.

    Article  CAS  Google Scholar 

  5. Coffey CJ, Kiernan MG, Sahebally SM, Jarrar A, Burke JP, Kiely PA, et al. Inclusion of the mesentery in ileocolic resection for Crohn’s disease is associated with reduced surgical recurrence. J Crohn’s Colitis. 2018;12(10):1139–50. https://doi.org/10.1093/ecco-jcc/jjx187.

    Article  Google Scholar 

  6. Coffey JC, Walsh D, Byrnes KG, Hohenberger W, Heald RJ. Mesentery - a ‘New’ organ. Emerg Top Life Sci. 2020;4(2):191–206. https://doi.org/10.1042/etls20200006.

    Article  Google Scholar 

  7. Byrnes KG, Walsh D, Walsh LG, Coffey DM, Ullah MF, Mirapeix R, et al. The development and structure of the mesentery. Commun Biol. 2021;4(1):982. https://doi.org/10.1038/s42003-021-02496-1.

    Article  Google Scholar 

  8. Coffey JC, Byrnes KG, Walsh DJ, Cunningham RM. Update on the mesentery: structure, function, and role in disease. Lancet Gastroenterol Hepatol. 2022;7(1):96–106. https://doi.org/10.1016/s2468-1253(21)00179-5.

    Article  Google Scholar 

  9. Steffen EK, Berg RD, Deitch EA. Comparison of translocation rates of various indigenous bacteria from the gastrointestinal tract to the mesenteric lymph node. J Infect Dis. 1988;157(5):1032–8. https://doi.org/10.1093/infdis/157.5.1032.

    Article  CAS  Google Scholar 

  10. Sagar PM, MacFie J, Sedman P, May J, Mancey-Jones B, Johnstone D. Intestinal obstruction promotes gut translocation of bacteria. Dis Colon Rectum. 1995;38(6):640–4. https://doi.org/10.1007/bf02054126.

    Article  CAS  Google Scholar 

  11. Fink MP. Gastrointestinal mucosal injury in experimental models of shock, trauma, and sepsis. Crit Care Med. 1991;19(5):627–41. https://doi.org/10.1097/00003246-199105000-00009.

    Article  CAS  Google Scholar 

  12. Chan Y-L, Cheng CSK, Ng P-W. Mesenteric actinomycosis. Abdom Radiol. 1993;18(3):286–7. https://doi.org/10.1007/BF00198125.

    Article  CAS  Google Scholar 

  13. Havell EA, Beretich GR Jr, Carter PB. The mucosal phase of Listeria infection. Immunobiology. 1999;201(2):164–77. https://doi.org/10.1016/s0171-2985(99)80056-4.

    Article  CAS  Google Scholar 

  14. Gorbach SL, Nahas L, Lerner PI, Weinstein L. Studies of intestinal microflora. I. Effects of diet, age, and periodic sampling on numbers of fecal microorganisms in man. Gastroenterology. 1967;53(6):845–55.

    Article  CAS  Google Scholar 

  15. Finegold SM. Intestinal bacteria — the role they play in normal physiology, pathologic physiology, and infection. Calif Med. 1969;110(6):455–9.

    CAS  Google Scholar 

  16. Toccalino H, Fagundes Neto V. Multiple channel tube for intestinal bacteriological samples. Acta Gastroenterol Latinoam. 1973;5(3):151–3.

    CAS  Google Scholar 

  17. Dunne C. Adaptation of bacteria to the intestinal niche: probiotics and gut disorder. Inflamm Bowel Dis. 2001;7(2):136–45. https://doi.org/10.1097/00054725-200105000-00010.

    Article  CAS  Google Scholar 

  18. Dunne C, O’Mahony L, Murphy L, Thornton G, Morrissey D, O’Halloran S, et al. In vitro selection criteria for probiotic bacteria of human origin: correlation with in vivo findings. Am J Clin Nutr. 2001;73(2 Suppl):386s–92s. https://doi.org/10.1093/ajcn/73.2.386s.

    Article  CAS  Google Scholar 

  19. Dunne C, Shanahan F. Role of probiotics in the treatment of intestinal infections and inflammation. Curr Opin Gastroenterol. 2002;18(1):40–5. https://doi.org/10.1097/00001574-200201000-00007.

    Article  Google Scholar 

  20. Uhlig HH, Powrie F. Dendritic cells and the intestinal bacterial flora: a role for localized mucosal immune responses. J Clin Invest. 2003;112(5):648–51. https://doi.org/10.1172/jci19545.

    Article  CAS  Google Scholar 

  21. Dunne C, Kelly P, O’Halloran S, Soden D, Bennett M, Wright AV, et al. Mechanisms of adherence of a probiotic Lactobacillus strain during and after in vivo assessment in ulcerative colitis patients. Microb Ecol Health Dis. 2004;16(2–3):96–104. https://doi.org/10.1080/08910600410032295.

    Article  CAS  Google Scholar 

  22. Kelly P, Maguire PB, Bennett M, Fitzgerald DJ, Edwards RJ, Thiede B, et al. Correlation of probiotic Lactobacillus salivarius growth phase with its cell wall-associated proteome. FEMS Microbiol Lett. 2005;252(1):153–9. https://doi.org/10.1016/j.femsle.2005.08.051.

    Article  CAS  Google Scholar 

  23. Ding Z, Wang W, Zhang K, Ming F, Yangdai T, Xu T, et al. Novel scheme for non-invasive gut bioinformation acquisition with a magnetically controlled sampling capsule endoscope. Gut. 2021;70(12):2297–306. https://doi.org/10.1136/gutjnl-2020-322465.

    Article  CAS  Google Scholar 

  24. Berg RD. Mechanisms confining indigenous bacteria to the gastrointestinal tract. Am J Clin Nutr. 1980;33(11 Suppl):2472–84. https://doi.org/10.1093/ajcn/33.11.2472.

    Article  CAS  Google Scholar 

  25. Berg RD. Promotion of the translocation of enteric bacteria from the gastrointestinal tracts of mice by oral treatment with penicillin, clindamycin, or metronidazole. Infect Immun. 1981;33(3):854–61. https://doi.org/10.1128/iai.33.3.854-861.1981.

    Article  CAS  Google Scholar 

  26. Maejima K, Deitch E, Berg R. Promotion by burn stress of the translocation of bacteria from the gastrointestinal tracts of mice. Arch Surg. 1984;119(2):166–72. https://doi.org/10.1001/archsurg.1984.01390140032006.

    Article  CAS  Google Scholar 

  27. Deitch EA, Berg R, Specian R. Endotoxin promotes the translocation of bacteria from the gut. Arch Surg. 1987;122(2):185–90. https://doi.org/10.1001/archsurg.1987.01400140067008.

    Article  CAS  Google Scholar 

  28. Steffen EK, Berg RD. Relationship between cecal population levels of indigenous bacteria and translocation to the mesenteric lymph nodes. Infect Immun. 1983;39(3):1252–9. https://doi.org/10.1128/iai.39.3.1252-1259.1983.

    Article  CAS  Google Scholar 

  29. Tokyay R, Zeigler ST, Loick HM, Heggers JP, De la Garza P, Traber DL, et al. Mesenteric lymphadenectomy prevents postburn systemic spread of translocated bacteria. Arch Surg. 1992;127(4):384–8. https://doi.org/10.1001/archsurg.1992.01420040026003.

    Article  CAS  Google Scholar 

  30. Runyon BA, Squier S, Borzio M. Translocation of gut bacteria in rats with cirrhosis to mesenteric lymph nodes partially explains the pathogenesis of spontaneous bacterial peritonitis. J Hepatol. 1994;21(5):792–6. https://doi.org/10.1016/s0168-8278(94)80241-6.

    Article  CAS  Google Scholar 

  31. Llovet JM, Bartolí R, March F, Planas R, Viñado B, Cabré E, et al. Translocated intestinal bacteria cause spontaneous bacterial peritonitis in cirrhotic rats: molecular epidemiologic evidence. J Hepatol. 1998;28(2):307–13. https://doi.org/10.1016/0168-8278(88)80018-7.

    Article  CAS  Google Scholar 

  32. Brooks SG, May J, Sedman P, Tring I, Johnstone D, Mitchell CJ, et al. Translocation of enteric bacteria in humans. Br J Surg. 1993;80(7):901–2. https://doi.org/10.1002/bjs.1800800733.

    Article  CAS  Google Scholar 

  33. MacFie J. Bacterial translocation in surgical patients. Ann R Coll Surg Engl. 1997;79(3):183–9.

    CAS  Google Scholar 

  34. Nishigaki E, Abe T, Yokoyama Y, Fukaya M, Asahara T, Nomoto K, et al. The detection of intraoperative bacterial translocation in the mesenteric lymph nodes is useful in predicting patients at high risk for postoperative infectious complications after esophagectomy. Ann Surg. 2014;259(3):477–84. https://doi.org/10.1097/SLA.0b013e31828e39e8.

    Article  Google Scholar 

  35. Yokoyama Y, Fukaya M, Mizuno T, Ebata T, Asahara T, Nagino M. Clinical importance of “occult-bacterial translocation” in patients undergoing highly invasive gastrointestinal surgery: a review. Surg Today. 2021;51(4):485–92. https://doi.org/10.1007/s00595-020-02126-z.

    Article  CAS  Google Scholar 

  36. Cregan J, Hayward NJ. Bacterial content of healthy small intestine. BMJ. 1953;1(4824):1356–9. https://doi.org/10.1136/bmj.1.4824.1356.

    Article  CAS  Google Scholar 

  37. van Houte J, Gibbons RJ. Studies of the cultivable flora of normal human feces. Antonie Van Leeuwenhoek. 1966;32(1):212–22. https://doi.org/10.1007/bf02097463.

    Article  Google Scholar 

  38. Drasar BS, Shiner M, McLeod GM. Studies on the intestinal flora. Gastroenterology. 1969;56(1):71–9. https://doi.org/10.1016/S0016-5085(69)80067-3.

    Article  CAS  Google Scholar 

  39. Drasar BS, Shiner M. Studies on the intestinal flora. II. Bacterial flora of the small intestine in patients with gastrointestinal disorders. Gut. 1969;10(10):812–9. https://doi.org/10.1136/gut.10.10.812.

    Article  CAS  Google Scholar 

  40. Simon GL, Gorbach SL. Intestinal flora in health and disease. Gastroenterology. 1984;86(1):174–93.

    Article  CAS  Google Scholar 

  41. Sartor RB. Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol. 2006;3(7):390–407. https://doi.org/10.1038/ncpgasthep0528.

    Article  CAS  Google Scholar 

  42. Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet. 2012;380(9853):1590–605. https://doi.org/10.1016/s0140-6736(12)60026-9.

    Article  Google Scholar 

  43. Keighley MR, Arabi Y, Dimock F, Burdon DW, Allan RN, Alexander-Williams J. Influence of inflammatory bowel disease on intestinal microflora. Gut. 1978;19(12):1099–104. https://doi.org/10.1136/gut.19.12.1099.

    Article  CAS  Google Scholar 

  44. Thadepalli H, Lou SMA, Bach VT, Matsui TK, Mandal AK. Microflora of the human small intestine. Am J Surg. 1979;138(6):845–50. https://doi.org/10.1016/0002-9610(79)90309-X.

    Article  CAS  Google Scholar 

  45. Gorbach SL, Plaut AG, Nahas L, Weinstein L, Spanknebel G, Levitan R. Studies of intestinal microflora. II. Microorganisms of the small intestine and their relations to oral and fecal flora. Gastroenterology. 1967;53(6):856–67.

    Article  CAS  Google Scholar 

  46. Hartley CL, Neumann CS, Richmond MH. Adhesion of commensal bacteria to the large intestine wall in humans. Infect Immun. 1979;23(1):128–32. https://doi.org/10.1128/iai.23.1.128-132.1979.

    Article  CAS  Google Scholar 

  47. Nelson DP, Mata LJ. Bacterial flora associated with the human gastrointestinal mucosa. Gastroenterology. 1970;58(1):56–61. https://doi.org/10.1016/S0016-5085(70)80093-2.

    Article  CAS  Google Scholar 

  48. Peach S, Lock MR, Katz D, Todd IP, Tabaqchali S. Mucosal-associated bacterial flora of the intestine in patients with Crohn’s disease and in a control group. Gut. 1978;19(11):1034–42. https://doi.org/10.1136/gut.19.11.1034.

    Article  CAS  Google Scholar 

  49. Plaut AG, Gorbach SL, Nahas L, Weinstein L, Spanknebel G, Levitan R. Studies of intestinal microflora. 3. The microbial flora of human small intestinal mucosa and fluids. Gastroenterology. 1967;53(6):868–73.

    Article  CAS  Google Scholar 

  50. Fiocchi C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology. 1998;115(1):182–205. https://doi.org/10.1016/S0016-5085(98)70381-6.

    Article  CAS  Google Scholar 

  51. Ji B, Nielsen J. From next-generation sequencing to systematic modeling of the gut microbiome. Front Genet. 2015;6:219. https://doi.org/10.3389/fgene.2015.00219.

    Article  CAS  Google Scholar 

  52. Schirmer M, Franzosa EA, Lloyd-Price J, McIver LJ, Schwager R, Poon TW, et al. Dynamics of metatranscription in the inflammatory bowel disease gut microbiome. Nat Microbiol. 2018;3(3):337–46. https://doi.org/10.1038/s41564-017-0089-z.

    Article  CAS  Google Scholar 

  53. Laffineur G, Lescut D, Vincent P, Quandalle P, Wurtz A, Colombel JF. [Bacterial translocation in Crohn disease]. Gastroenterol Clin Biol. 1992;16(10):777–81.

    Google Scholar 

  54. O’Boyle CJ, MacFie J, Mitchell CJ, Johnstone D, Sagar PM, Sedman PC. Microbiology of bacterial translocation in humans. Gut. 1998;42(1):29–35. https://doi.org/10.1136/gut.42.1.29.

    Article  Google Scholar 

  55. Sedman PC, Macfie J, Sagar P, Mitchell CJ, May J, Mancey-Jones B, et al. The prevalence of gut translocation in humans. Gastroenterology. 1994;107(3):643–9. https://doi.org/10.1016/0016-5085(94)90110-4.

    Article  CAS  Google Scholar 

  56. Ambrose NS, Johnson M, Burdon DW, Keighley MR. Incidence of pathogenic bacteria from mesenteric lymph nodes and ileal serosa during Crohn’s disease surgery. Br J Surg. 1984;71(8):623–5. https://doi.org/10.1002/bjs.1800710821.

    Article  CAS  Google Scholar 

  57. Takesue Y, Ohge H, Uemura K, Imamura Y, Murakami Y, Yokoyama T, et al. Bacterial translocation in patients with Crohn’s disease undergoing surgery. Dis Colon Rectum. 2002;45(12):1665–71. https://doi.org/10.1097/01.dcr.0000034515.66401.8b.

    Article  Google Scholar 

  58. Gay J, Tachon M, Neut C, Beclin E, Cheng Y, Berrebi D, et al. Mesenteric adipose tissue is colonized by bacterial flora and expresses pathogen recognition receptors in Crohn’s disease. Gastroenterology. 2005;128(Suppl 2):A503.

    Google Scholar 

  59. Batra A, Heimesaat MM, Bereswill S, Fischer A, Glauben R, Kunkel D, et al. Mesenteric fat - control site for bacterial translocation in colitis? Mucosal Immunol. 2012;5(5):580–91. https://doi.org/10.1038/mi.2012.33.

    Article  CAS  Google Scholar 

  60. Peyrin-Biroulet L, Gonzalez F, Dubuquoy L, Rousseaux C, Dubuquoy C, Decourcelle C, et al. Mesenteric fat as a source of C reactive protein and as a target for bacterial translocation in Crohn’s disease. Gut. 2012;61(1):78–85. https://doi.org/10.1136/gutjnl-2011-300370.

    Article  CAS  Google Scholar 

  61. Zulian A, Cancello R, Ruocco C, Gentilini D, Di Blasio AM, Danelli P, et al. Differences in visceral fat and fat bacterial colonization between ulcerative colitis and Crohn’s disease. An in vivo and in vitro study. PLoS One. 2013;8(10):e78495. https://doi.org/10.1371/journal.pone.0078495.

    Article  CAS  Google Scholar 

  62. Lin Y, Lee H, Berg AH, Lisanti MP, Shapiro L, Scherer PE. The Lipopolysaccharide-activated toll-like receptor (TLR)-4 induces synthesis of the closely related receptor TLR-2 in adipocytes. J Biol Chem. 2000;275(32):24255–63. https://doi.org/10.1074/jbc.M002137200.

    Article  CAS  Google Scholar 

  63. Chung S, Lapoint K, Martinez K, Kennedy A, Boysen Sandberg M, McIntosh MK. Preadipocytes mediate lipopolysaccharide-induced inflammation and insulin resistance in primary cultures of newly differentiated human adipocytes. Endocrinology. 2006;147(11):5340–51. https://doi.org/10.1210/en.2006-0536.

    Article  CAS  Google Scholar 

  64. Batra A, Pietsch J, Fedke I, Glauben R, Okur B, Stroh T, et al. Leptin-dependent toll-like receptor expression and responsiveness in preadipocytes and adipocytes. Am J Pathol. 2007;170(6):1931–41. https://doi.org/10.2353/ajpath.2007.060699.

    Article  CAS  Google Scholar 

  65. Creely SJ, McTernan PG, Kusminski CM, Fisher FM, Da Silva NF, Khanolkar M, et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab. 2007;292(3):E740–7. https://doi.org/10.1152/ajpendo.00302.2006.

    Article  CAS  Google Scholar 

  66. Poulain-Godefroy O, Froguel P. Preadipocyte response and impairment of differentiation in an inflammatory environment. Biochem Biophys Res Commun. 2007;356(3):662–7. https://doi.org/10.1016/j.bbrc.2007.03.053.

    Article  CAS  Google Scholar 

  67. Stroh T, Batra A, Glauben R, Fedke I, Erben U, Kroesen A, et al. Nucleotide oligomerization domains 1 and 2: regulation of expression and function in preadipocytes. J Immunol. 2008;181(5):3620–7. https://doi.org/10.4049/jimmunol.181.5.3620.

    Article  CAS  Google Scholar 

  68. Zulian A, Cancello R, Micheletto G, Gentilini D, Gilardini L, Danelli P, et al. Visceral adipocytes: old actors in obesity and new protagonists in Crohn’s disease? Gut. 2012;61(1):86–94. https://doi.org/10.1136/gutjnl-2011-300391.

    Article  CAS  Google Scholar 

  69. Dowling L, Jakeman P, Norton C, Skelly MM, Yousuf H, Kiernan MG, et al. Adults with Crohn’s disease exhibit elevated gynoid fat and reduced android fat irrespective of disease relapse or remission. Sci Rep. 2021;11(1):19258. https://doi.org/10.1038/s41598-021-98798-9.

    Article  CAS  Google Scholar 

  70. Bryant RV, Trott MJ, Bartholomeusz FD, Andrews JM. Systematic review: body composition in adults with inflammatory bowel disease. Aliment Pharmacol Ther. 2013;38(3):213–25. https://doi.org/10.1111/apt.12372.

    Article  CAS  Google Scholar 

  71. Boparai G, Kedia S, Kandasamy D, Sharma R, Madhusudhan KS, Dash NR, et al. Combination of sarcopenia and high visceral fat predict poor outcomes in patients with Crohn’s disease. Eur J Clin Nutr. 2021;75(10):1491–8. https://doi.org/10.1038/s41430-021-00857-x.

    Article  Google Scholar 

  72. Eder P, Adler M, Dobrowolska A, Kamhieh-Milz J, Witowski J. The role of adipose tissue in the pathogenesis and therapeutic outcomes of inflammatory bowel disease. Cells. 2019;8(6):628. https://doi.org/10.3390/cells8060628.

    Article  CAS  Google Scholar 

  73. Zielińska A, Siwiński P, Sobolewska-Włodarczyk A, Wiśniewska-Jarosińska M, Fichna J, Włodarczyk M. The role of adipose tissue in the pathogenesis of Crohn’s disease. Pharmacol Rep. 2019;71(1):105–11. https://doi.org/10.1016/j.pharep.2018.09.011.

    Article  CAS  Google Scholar 

  74. Kiernan MG, Coffey JC, McDermott K, Cotter PD, Cabrera-Rubio R, Kiely PA, et al. The human mesenteric lymph node microbiome differentiates between Crohn’s disease and ulcerative colitis. J Crohn’s Colitis. 2019;13(1):58–66. https://doi.org/10.1093/ecco-jcc/jjy136.

    Article  Google Scholar 

  75. Feng Q, Xu XT, Zhou Y, Yan YQ, Ran ZH, Zhu J. Creeping fat in patients with ileo-colonic Crohn’s disease correlates with disease activity and severity of inflammation: a preliminary study using energy spectral computed tomography. J Dig Dis. 2018;19(8):475–84. https://doi.org/10.1111/1751-2980.12652.

    Article  CAS  Google Scholar 

  76. Althoff P, Schmiegel W, Lang G, Nicolas V, Brechmann T. Creeping fat assessed by small bowel MRI is linked to bowel damage and abdominal surgery in Crohn’s disease. Dig Dis Sci. 2019;64(1):204–12. https://doi.org/10.1007/s10620-018-5303-1.

    Article  Google Scholar 

  77. Mao R, Kurada S, Gordon IO, Baker ME, Gandhi N, McDonald C, et al. The mesenteric fat and intestinal muscle interface: creeping fat influencing stricture formation in Crohn’s disease. Inflamm Bowel Dis. 2018;25:421. https://doi.org/10.1093/ibd/izy331.

    Article  Google Scholar 

  78. Bilski J, Mazur-Bialy A, Wojcik D, Surmiak M, Magierowski M, Sliwowski Z, et al. Role of obesity, mesenteric adipose tissue, and adipokines in inflammatory bowel diseases. Biomolecules. 2019;9(12):780. https://doi.org/10.3390/biom9120780.

    Article  CAS  Google Scholar 

  79. Kiernan MG, Coffey JC, Sahebally SM, Tibbitts P, Lyons EM, O’Leary E, et al. Systemic molecular mediators of inflammation differentiate between Crohn’s disease and ulcerative colitis, implicating threshold levels of IL-10 and relative ratios of pro-inflammatory cytokines in therapy. J Crohn’s Colitis. 2020;14(1):118–29. https://doi.org/10.1093/ecco-jcc/jjz117.

    Article  Google Scholar 

  80. Hong PY, Croix JA, Greenberg E, Gaskins HR, Mackie RI. Pyrosequencing-based analysis of the mucosal microbiota in healthy individuals reveals ubiquitous bacterial groups and micro-heterogeneity. PLoS One. 2011;6(9):e25042. https://doi.org/10.1371/journal.pone.0025042.

    Article  CAS  Google Scholar 

  81. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207–14. https://doi.org/10.1038/nature11234.

    Article  CAS  Google Scholar 

  82. Faith JJ, Guruge JL, Charbonneau M, Subramanian S, Seedorf H, Goodman AL, et al. The long-term stability of the human gut microbiota. Science (New York, NY). 2013;341(6141):1237439. https://doi.org/10.1126/science.1237439.

    Article  CAS  Google Scholar 

  83. Shanahan F. The colonic microbiota in health and disease. Curr Opin Gastroenterol. 2013;29(1):49–54. https://doi.org/10.1097/MOG.0b013e32835a3493.

    Article  CAS  Google Scholar 

  84. Frank DN, St. Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A. 2007;104(34):13780–5. https://doi.org/10.1073/pnas.0706625104.

    Article  CAS  Google Scholar 

  85. Kostic AD, Xavier RJ, Gevers D. The microbiome in inflammatory bowel diseases: current status and the future ahead. Gastroenterology. 2014;146(6):1489–99. https://doi.org/10.1053/j.gastro.2014.02.009.

    Article  CAS  Google Scholar 

  86. He Z, Wu J, Gong J, Ke J, Ding T, Zhao W, et al. Microbiota in mesenteric adipose tissue from Crohn’s disease promote colitis in mice. Microbiome. 2021;9(1):228. https://doi.org/10.1186/s40168-021-01178-8.

    Article  CAS  Google Scholar 

  87. Ha CWY, Martin A, Sepich-Poore GD, Shi B, Wang Y, Gouin K, et al. Translocation of viable gut microbiota to mesenteric adipose drives formation of creeping fat in humans. Cell. 2020;183(3):666–83.e17. https://doi.org/10.1016/j.cell.2020.09.009.

    Article  CAS  Google Scholar 

  88. Kaakoush NO. Insights into the role of erysipelotrichaceae in the human host. Front Cell Infect Microbiol. 2015;5:84. https://doi.org/10.3389/fcimb.2015.00084.

    Article  CAS  Google Scholar 

  89. O’Brien CL, Pavli P, Gordon DM, Allison GE. Detection of bacterial DNA in lymph nodes of Crohn’s disease patients using high throughput sequencing. Gut. 2014;63(10):1596–606. https://doi.org/10.1136/gutjnl-2013-305320.

    Article  Google Scholar 

  90. Kiely CJ, Pavli P, O’Brien CL. The microbiome of translocated bacterial populations in patients with and without inflammatory bowel disease. Intern Med J. 2018;48(11):1346–54. https://doi.org/10.1111/imj.13998.

    Article  CAS  Google Scholar 

  91. Cave DR, Mitchell DN, Brooke BN. Evidence of an agent transmissible from ulcerative colitis tissue. Lancet. 1976;1(7973):1311–5. https://doi.org/10.1016/s0140-6736(76)92649-0.

    Article  CAS  Google Scholar 

  92. Phillpotts RJ, Hermon-Taylor J, Teich NM, Brooke BN. A search for persistent virus infection in Crohn’s disease. Gut. 1980;21(3):202–7. https://doi.org/10.1136/gut.21.3.202.

    Article  CAS  Google Scholar 

  93. Guarner F, Malagelada JR. Role of bacteria in experimental colitis. Best Pract Res Clin Gastroenterol. 2003;17(5):793–804. https://doi.org/10.1016/s1521-6918(03)00068-4.

    Article  CAS  Google Scholar 

  94. Akashi K, Yokoyama Y, Mizuno T, Abe T, Fukaya M, Asahara T, et al. Association between preoperative muscle mass and intraoperative bacterial translocation in patients undergoing hepatectomy, pancreatoduodenectomy, and esophagectomy. Ann Surg Oncol. 2019;26(13):4805–13. https://doi.org/10.1245/s10434-019-07707-y.

    Article  Google Scholar 

  95. Cook MG. The size and histological appearances of mesenteric lymph nodes in Crohn’s disease. Gut. 1972;13(12):970–2. https://doi.org/10.1136/gut.13.12.970.

    Article  CAS  Google Scholar 

  96. Guillou PJ, Brennan TG, Giles GR. Lymphocyte transformation in the mesenteric lymph nodes of patients with Crohn’s disease. Gut. 1973;14(1):20–4. https://doi.org/10.1136/gut.14.1.20.

    Article  CAS  Google Scholar 

  97. Diehl GE, Longman RS, Zhang JX, Breart B, Galan C, Cuesta A, et al. Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX(3)CR1(hi) cells. Nature. 2013;494(7435):116–20. https://doi.org/10.1038/nature11809.

    Article  CAS  Google Scholar 

  98. Sampietro GM, Maconi G, Colombo F, Dilillo D, Fiorina P, D’Addio F, et al. Prevalence and significance of mesentery thickening and lymph nodes enlargement in Crohn’s disease. Dig Liver Dis. 2021;54:490. https://doi.org/10.1016/j.dld.2021.06.030.

    Article  CAS  Google Scholar 

  99. Dickson I. Creeping fat in Crohn’s disease explained. Nat Rev Gastroenterol Hepatol. 2020;17(12):713. https://doi.org/10.1038/s41575-020-00379-0.

    Article  Google Scholar 

  100. Pierce ES. Where are all the mycobacterium avium subspecies paratuberculosis in patients with Crohn’s disease? PLoS Pathog. 2009;5(3):1–11. https://doi.org/10.1371/journal.ppat.1000234.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the work of the Departments of Gastroenterology and Surgery at University Hospital Limerick and that of the technician team at the School of Medicine, University of Limerick.

Funding Source

No funding.

Authors’ Contribution Statement Using CRediT with Degree of Contribution

MK: Writing—original draft (equal); Writing—review and editing (supporting), Data curation (equal); Methodology (equal). SSD: Writing—original draft (supporting); Writing—review and editing (supporting). KM: Writing—review and editing (supporting), Methodology (supporting). PJ: Writing—review and editing (supporting), Data curation (supporting); Methodology (supporting). BG: Conceptualization (supporting); review and editing (supporting). TT: Methodology (supporting); review and editing (supporting). SK: Conceptualization (supporting); Writing—original draft (supporting); review and editing (supporting). JCC: Writing—review and editing (supporting), Data curation (supporting); Methodology (supporting). CPD: Conceptualization (lead); Writing—original draft (lead); Data curation (lead); Methodology (lead); Writing—review and editing (lead).

Compliance with Ethical Standards

The work presented here has been approved by the appropriate institutional ethics committee and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from individual participants.

Conflict of Interest Statement

The authors certify that they have no affiliations with or involvement in any organisation or entity with any financial interest, or non-financial interest in the subject matter or materials directly or indirectly related to the work submitted for publication.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Colum P. Dunne .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kiernan, M.G. et al. (2023). Mesenteric Microbiology and Inflammatory Bowel Disease: Improved Understanding Due to Accelerating Innovation and Sophistication of Molecular Technology. In: Coffey, J.C. (eds) The Mesentery and Inflammation . Progress in Inflammation Research, vol 90. Springer, Cham. https://doi.org/10.1007/978-3-031-17774-3_7

Download citation

Publish with us

Policies and ethics