Gut origin of sepsis: a prospective study investigating associations between bacterial translocation, gastric microflora, and septic morbidity

AIMSTo investigate the “gut origin of sepsis” hypothesis.METHODSProspective controlled study of 279 surgical patients in which cultures of nasogastric aspirates were compared with those obtained from mesenteric lymph nodes taken at laparotomy and the organisms cultured from subsequent septic complications. Bacterial translocation was confirmed if positive cultures were obtained from mesenteric lymph nodes. Postoperative sepsis was defined as any positive culture in the postoperative period. Bacterial species obtained in gastric microflora, mesenteric lymph nodes, and postoperative septic complications were compared.RESULTSOnly 85/279 patients (31%) had a sterile nasogastric aspirate; the most frequently identified organism was Candida spp. (54%) and the most common enteric organism cultured was E coli (20%). Multiple organisms were isolated in 39% and occurred more frequently in patients aged over 70 years, those undergoing non-elective surgery, and in those requiring proximal gastrointestinal surgery. Postoperative sepsis was more common in these patients. Bacterial translocation occurred in 21% and was significantly more frequent in those with multiple organisms in their nasogastric aspirates. E coli was the commonest organism isolated from the lymph node specimens (48%) and septic foci (53%). Fungal translocation did not occur. An identical genus was identified in the nasogastric aspirate and the septic focus in 30% of patients, in the nasogastric aspirate and the lymph node in 31%, and in the lymph node and a postoperative septic focus in 45%.CONCLUSIONSProximal gut colonisation is associated with both increased bacterial translocation and septic morbidity. The commonality of organisms identified supports the gut origin of sepsis hypothesis.

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Microbiology of bacterial translocation in humans

Gut ◽

10.1136/gut.42.1.29 ◽

1998 ◽

Vol 42 (1) ◽

pp. 29-35 ◽

Cited By ~ 232

Author(s):

C J O’Boyle ◽

J MacFie ◽

C J Mitchell ◽

D Johnstone ◽

P M Sagar ◽

...

Keyword(s):

Lymph Nodes ◽

Bacterial Translocation ◽

Intestinal Flora ◽

Enteric Bacteria ◽

Surgical Patients ◽

Postoperative Sepsis ◽

Mesenteric Lymph Nodes ◽

Septic Complications ◽

Mesenteric Lymph ◽

Postoperative Septic Complications

Background—Gut translocation of bacteria has been shown in both animal and human studies. Evidence from animal studies that links bacterial translocation to the development of postoperative sepsis and multiple organ failure has yet to be confirmed in humans.Aims—To examine the spectrum of bacteria involved in translocation in surgical patients undergoing laparotomy and to determine the relation between nodal migration of bacteria and the development of postoperative septic complications.Methods—Mesenteric lymph nodes (MLN), serosal scrapings, and peripheral blood from 448 surgical patients undergoing laparotomy were analysed using standard microbiological techniques.Results—Bacterial translocation was identified in 69 patients (15.4%). The most common organism identified wasEscherichia coli (54%). Both enteric bacteria, typical of indigenous intestinal flora, and non-enteric bacteria were isolated. Postoperative septic complications developed in 104 patients (23%). Enteric organisms were responsible in 74% of patients. Forty one per cent of patients who had evidence of bacterial translocation developed sepsis compared with 14% in whom no organisms were cultured (p<0.001). Septic morbidity was more frequent when a greater diversity of bacteria resided within the MLN, but this was not statistically significant.Conclusion—Bacterial translocation is associated with a significant increase in the development of postoperative sepsis in surgical patients. The organisms responsible for septic morbidity are similar in spectrum to those observed in the mesenteric lymph nodes. These data strongly support the gut origin hypothesis of sepsis in humans.

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Bacterial Translocation as a Cause of Postoperative Sepsis in Surgical Patients Undergoing Laparotomy

Journal of Lumbini Medical College ◽

10.22502/jlmc.v2i2.53 ◽

2014 ◽

Vol 2 (2) ◽

pp. 28

Author(s):

Neeraj Thapa ◽

Bhairav Kumar Hamal ◽

Nagendra Prashad Yadav ◽

Ghanashyam Thapa

Keyword(s):

Lymph Nodes ◽

Bacterial Translocation ◽

Enteric Bacteria ◽

Surgical Patients ◽

Postoperative Sepsis ◽

Mesenteric Lymph Nodes ◽

Septic Complications ◽

Emergency Procedures ◽

Mesenteric Lymph ◽

Postoperative Septic Complications

Introduction: Bacterial translocation is the invasion of indigenous intestinal bacteria through the gut mucosa to normally sterile tissues and the internal organs. Objective of the study is to examine the spectrum of bacteria involved in translocation in surgical patients undergoing laparotomy and to determine the relation between nodal migration of bacteria and the development of postoperative septic complications. Methods: Mesenteric lymph nodes (MLN)culture was done in patients undergoing elective and emergency surgeries fulfilling the inclusion criteria. Results:Bacterial translocation was identified in 22 (44.8%) patients. The most common organism identified was Escherichia coli (n=11, 50%). Both enteric bacteria, typical of indigenous intestinal flora, and non-enteric bacteria were isolated. Postoperative septic complications developed in four (11%) patients. Septic morbidity was more frequent when a greater diversity of bacteria resided within the mesenteric lymph nodes. Conclusion: Bacterial translocation is associated with an increase in the development of postoperative sepsis in surgical patients. The organisms responsible for septic morbidity are similar in spectrum to those observed in the mesenteric lymph nodes. These data strongly support the gut origin hypothesis of sepsis in humans. Besides, there is increased bacterial translocation in patients undergoing emergency procedures. Keywords: bacteria • laparotomy • postoperative • sepsis • translocation

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Portal Hypertension Promotes Bacterial Translocation in Rats Mono- and Non Mono-Associated with Escherichia Coli C25

HPB Surgery ◽

10.1155/1994/57549 ◽

1994 ◽

Vol 8 (2) ◽

pp. 95-100 ◽

Cited By ~ 2

Author(s):

Jean-Nicolas Vauthey ◽

Petra Duda ◽

Anthony M. Wheatley ◽

Philippe Gertsch

Keyword(s):

Escherichia Coli ◽

Portal Hypertension ◽

Lymph Nodes ◽

Bacterial Translocation ◽

Hypovolemic Shock ◽

Portal Vein Ligation ◽

Mesenteric Lymph Nodes ◽

Septic Complications ◽

Mesenteric Lymph ◽

High Incidence

The basis for the high incidence of infectious complications in portal hypertension (PHT) remains unclear. The hypothesis that PHT induces bacterial translocation (BT) was tested in a rat model with or without mono-association with streptomycin resistant Escherichia coli C25 and with or without hypovolemic shock. PHT was achieved by partial portal vein ligation and three weeks later hypovolemic shock (HS) was induced. Blood, liver, spleen and mesenteric lymph nodes cultures were performed twenty-four hours later.PHT promoted BT to mesenteric lymph nodes in indigenous flora (4/6 [67%]) and mono-associated animals (7/9 [78%]) compared to sham laparotomy and sham shock (SL + SS) animals (0/6 [0%] and 2/9 [22%] respectively) (p = 0.03). The combination of PHT and HS resulted in increased mortality in mono-associated (7/15 [47%]) and non mono-associated animals (8/15 [53%]). No significant translocation was noted in liver and spleen and bacteremia was found only in the PHT + HS mono-associated animals (4/8 [50%]).PHT induces BT to mesenteric lymph nodes and this may account for the high incidence of septic complications associated witti PHT. In this model, the addition of HS to PHT leads to an increased mortality but without uniform translocation of the gut flora beyond mesenteric lymph nodes.

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Inhibition of Escherichia coli Translocation from the Gastrointestinal Tract by Normal Cecal Flora in Gnotobiotic or Antibiotic-Decontaminated Mice

Infection and Immunity ◽

10.1128/iai.29.3.1073-1081.1980 ◽

1980 ◽

Vol 29 (3) ◽

pp. 1073-1081

Author(s):

Rodney D. Berg

Keyword(s):

Escherichia Coli ◽

Gastrointestinal Tract ◽

Lymph Nodes ◽

Bacterial Flora ◽

Specific Pathogen Free ◽

Mesenteric Lymph Nodes ◽

E Coli ◽

Mesenteric Lymph ◽

Specific Pathogen ◽

Gnotobiotic Mice

Escherichia coli C25 maintained population levels of 10 9 to 10 10 per g of cecum and translocated to 100% of the middle mesenteric lymph nodes in gnotobiotic mice monoassociated with E. coli C25. Intragastric inoculation of these mice with the cecal contents from specific-pathogen-free mice reduced the population levels of E. coli C25 to 10 6 per g of cecum and completely inhibited translocation to the mesenteric lymph nodes. Intragastric inoculation with heat-treated, Formalintreated, or filtered cecal contents did not reduce the population levels of E. coli C25 or reduce the incidence of translocation of E. coli C25 to the mesenteric lymph nodes. Thus, viable bacteria apparently are required in the cecal contents inocula to reduce the population levels and the incidence of translocation of E. coli C25. Treatment with streptomycin plus bacitracin decreased the anaerobic bacterial levels in these gnotobiotic mice, allowing increased population levels of E. coli C25 and increased translocation to the mesenteric lymph nodes. E. coli C25 also translocated to the mesenteric lymph nodes of specific-pathogen-free mice treated with streptomycin and bacitracin before colonization with E. coli C25. The high cecal population levels of E. coli C25 in these antibiotic-decontaminated specific-pathogen-free mice apparently overwhelm any barrier to translocation exerted by the immunologically developed lamina propria of the specific-pathogen-free mice. Inoculation of gnotobiotic mice with a cecal flora also reduced the population levels of an indigenous strain of E. coli with a concomitant inhibition of translocation of the indigenous E. coli to the mesenteric lymph nodes. Thus, bacterial antagonism of the gastrointestinal population levels of certain indigenous bacteria, such as E. coli , by other members of the normal bacterial flora appears to be an important defense mechanism confining bacteria to the gastrointestinal tract.

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Immunocytochemistry of mesenteric lymph node fine-needle aspirates in the diagnosis of feline infectious peritonitis

Journal of Veterinary Diagnostic Investigation ◽

10.1177/1040638718825280 ◽

2019 ◽

Vol 31 (2) ◽

pp. 210-216 ◽

Cited By ~ 4

Author(s):

Sandra Felten ◽

Katrin Hartmann ◽

Stefanie Doerfelt ◽

Laura Sangl ◽

Johannes Hirschberger ◽

...

Keyword(s):

Lymph Node ◽

Lymph Nodes ◽

Mesenteric Lymph Node ◽

Complex Method ◽

Mesenteric Lymph Nodes ◽

Predictive Values ◽

Feline Infectious Peritonitis ◽

Fine Needle ◽

Fine Needle Aspirates ◽

Mesenteric Lymph

Immunohistochemistry (IHC) of tissue samples is considered the gold standard for diagnosing feline infectious peritonitis (FIP), and, in cats without body cavity effusion, IHC is the only method available to establish definitive antemortem diagnosis. However, IHC requires invasive tissue sample collection. We evaluated sensitivity and specificity of an immunocytochemical assay of fine-needle aspirates (FNAs) of mesenteric lymph nodes that can be obtained noninvasively by ultrasound-guided aspiration to diagnose FIP. FNAs of mesenteric lymph nodes were obtained postmortem from 41 cats suspected of having FIP based on clinical and/or laboratory findings. FIP was confirmed immunohistochemically in 30 cats. In the other 11 cats, a disease other than FIP, which explained the clinical signs, was diagnosed histopathologically. Immunocytochemistry (ICC) was performed as an avidin–biotin complex method using a monoclonal anti-FCoV IgG 2A. Sensitivity, specificity, negative and positive predictive values (NPV, PPV, respectively) including 95% confidence intervals (95% CIs) were determined. ICC was positive in 17 of 30 cats with FIP, but also in 1 of 11 control cats that was diagnosed with lymphoma. Sensitivity of ICC was 53% (95% CI: 34–72); specificity 91% (95% CI: 59–100); NPV 42% (95% CI: 22–63); and PPV 94% (95% CI: 71–100). In a lethal disease such as FIP, specificity is most important in order to avoid euthanasia of unaffected cats. Given that a false-positive result occurred and FIP was correctly detected in only approximately half of the cases of FIP, ICC of mesenteric lymph node FNA alone cannot reliably confirm or exclude FIP, but can be a helpful test in conjunction with other diagnostic measures.

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Bacterial Translocation to Mesenteric Lymph Nodes Increases in Chronic Portal Hypertensive Rats

Digestive Diseases and Sciences ◽

10.1007/s10620-009-1001-3 ◽

2009 ◽

Vol 55 (8) ◽

pp. 2244-2254 ◽

Cited By ~ 16

Author(s):

Miguel-Ángel Llamas ◽

María-Ángeles Aller ◽

Domingo Marquina ◽

María-Paz Nava ◽

Jaime Arias

Keyword(s):

Lymph Nodes ◽

Bacterial Translocation ◽

Hypertensive Rats ◽

Mesenteric Lymph Nodes ◽

Mesenteric Lymph

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Metastasis to lateral lymph nodes with no mesenteric lymph node involvement in low rectal cancer: a retrospective case series

10.21203/rs.3.rs-33839/v2 ◽

2020 ◽

Author(s):

Peng Li ◽

Zhichun Zhang ◽

Yuanda Zhou ◽

Qingsheng Zeng ◽

Xipeng Zhang ◽

...

Keyword(s):

Rectal Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Dissection ◽

Low Rectal Cancer ◽

Lateral Lymph Node Dissection ◽

Node Dissection ◽

Mesenteric Lymph Nodes ◽

Lateral Lymph Node ◽

Mesenteric Lymph

Abstract Purpose The aim of this study is to examine the pattern of lymph node metastasis (lateral vs. mesenteric lymph nodes) in low rectal cancer.Methods This retrospective analysis included all patients undergoing laparoscopic total mesorectal excision plus lateral lymph node dissection for advanced low rectal cancer (up to 8 cm from the anal verge) during a period from July 1, 2017 to August 31, 2019 at the Department of Colorectal Surgery, Tianjin Union Medical Center. The decision to conduct lateral lymph node dissection was based on positive findings in preoperative imaging assessments.Results A total of 42 patients were included in data analysis. Surgery was successfully completed as planned, without conversion to open surgery in any case. A minimal of 10 mesenteric lymph nodes and 1 lateral lymph node on each side were dissected in all patients. Pathologic examination of resected specimens showed no metastasis to either mesenteric or lateral lymph nodes in 7 (16.7%) case, metastasis to both mesenteric and lateral lymph nodes in 26 (61.9%) cases, metastasis to mesenteric but not lateral lymph nodes in 4 (9.5%) cases, and metastasis to lateral but not mesenteric lymph nodes in 5 (11.9%) cases (n=2 in the obturator region; n=3 in the iliac artery region).Conclusion A clinically significant proportion of low rectal cancer patients have metastasis to lateral lymph nodes without involvement of mesenteric lymph nodes. More carefully planned prospective studies are needed to verify this preliminary finding.

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91 Effects of antibiotics on growth performance, diarrhea, and bacterial translocation in weanling pigs experimentally infected with a pathogenic E. coli

Journal of Animal Science ◽

10.1093/jas/skz122.096 ◽

2019 ◽

Vol 97 (Supplement_2) ◽

pp. 53-53

Author(s):

Kwangwook Kim ◽

Yijie He ◽

Cynthia Jinno ◽

Seijoo Yang ◽

Minho Song ◽

...

Keyword(s):

Lymph Nodes ◽

Growth Performance ◽

Bacterial Translocation ◽

Low Dose ◽

Control Diet ◽

High Dose ◽

Post Inoculation ◽

Mesenteric Lymph Nodes ◽

Fecal Samples ◽

E Coli

Abstract The experiment was conducted to investigate the effects of antibiotics on growth performance, diarrhea, fecal β-hemolytic coliforms, and bacterial translocation of weaned pigs experimentally infected with F18 Escherichia coli (E. coli). Twenty-six pigs (6.88 ± 1.03 kg BW) were individually housed in disease containment rooms and randomly allotted to one of three treatments with 8–9 replicate pigs per treatment. The three dietary treatments were control diet and 2 additional diets supplemented with 0.5 or 50 mg/kg carbadox, respectively. The experiment lasted 18 d (7 d before and 11 d after first inoculation [d 0]). F18 E. coli inoculum was daily and orally as 1010 cfu/3 mL for 3 days. Growth performance was measured on d -7 to 0 before inoculation, and d 0 to 5 and 5 to 11 post-inoculation (PI). Diarrhea scores were daily checked throughout the experiment. Fecal samples were collected on d 2, 5, 8, and 11 PI to test the percentage of β-hemolytic coliforms in total coliforms. Bacterial translocation was measured in lymph nodes on d 5 and 11 PI. All data were analyzed by ANOVA using PROC MIXED of SAS. Pigs supplemented with high-dose of antibiotics had greater (P < 0.05) final BW and lower (P < 0.05) overall frequency of diarrhea, compared with pigs in control and low-dose antibiotics groups. Pigs supplemented with low-dose antibiotics had lowest (P < 0.05) ADG and feed efficiency from d 0 to 5 PI, and had highest (P < 0.05) percentage of β-hemolytic coliforms in fecal samples on d 2 and 5 PI, and greatest (P < 0.05) bacterial colonies in mesenteric lymph nodes on d 11 PI, compared with pigs in the other two groups. In conclusion, low dose antibiotic supplementation exacerbates the detrimental effects of E. coli infection on pig performance and diarrhea.

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MAGNITUDE AND PATTERN OF THYMIC LYMPHOCYTE MIGRATION IN NEONATAL MICE

Journal of Experimental Medicine ◽

10.1084/jem.135.4.907 ◽

1972 ◽

Vol 135 (4) ◽

pp. 907-923 ◽

Cited By ~ 60

Author(s):

D. D. Joel ◽

M. W. Hess ◽

H. Cottier

Keyword(s):

Bone Marrow ◽

Cell Migration ◽

Lymph Node ◽

Lymph Nodes ◽

Peyer's Patches ◽

Mesenteric Lymph Nodes ◽

Neonatal Mice ◽

Mesenteric Lymph ◽

The Mean ◽

Thymic Cell

Neonatal mice were given a subcapsular, intrathymic injection of thymidine-3H using a modified microneedle technique, and the migration of labeled cells to spleen, lymph nodes, Peyer's patches, and bone marrow was followed radioautographically with time. Assuming that nonlabeled lymphocytes migrated in the same manner as labeled lymphocytes, it can be concluded that the majority of lymphocytes present within mesenteric lymph nodes (74%) and Peyer's patches (61%), and a large proportion of those located in popliteal lymph nodes (40%) and the spleen (26%), were of thymic origin. Evidence is presented indicating that these are minimum values. The difference in the magnitude of thymic cell migration to gut-associated lymphoid tissue on the one hand and to the spleen and popliteal lymph node on the other hand was tentatively attributed to antigenic stimulation from the intestinal flora which develops during the first days of life. Thymus-derived lymphocytes were scattered throughout the lymph node cortex and splenic follicles. No noticeable thymic cell migration to the bone marrow was found. Labeling indices in the peripheral lymphoid organs paralleled those of cortical thymic lymphocytes suggesting the thymic cortex as the major source of migrants. By 2 days postinjection, the mean grain counts of labeled lymphocytes in all peripheral lymphoid tissues were higher than the mean grain counts of labeled lymphocytes in the thymus. At 7 days postinjection heavily labeled cells constituted 11–16% of the labeled population in peripheral tissues while they were absent from the thymic cortex. These results indicate that a fraction of thymus-derived cells, upon settling in the periphery, remained in, or reentered, a nonproliferative phase for at least 7 days. Conversely, many thymus-derived lymphocytes underwent division in the periphery and/or penetrated the intestinal epithelium. Since the relative number of thymus-derived cells found in the mesenteric lymph nodes of 1- and 2-day old mice was considerably higher than the percentage of cells at this site having the theta (θ) alloantigen, as reported by other authors, the possibility exists that θ-antigen on thymus-derived lymphocytes may, at least in a fraction of these cells, no longer be detectable as they reach the peripheral organs.

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Metastasis to lateral lymph nodes with no mesenteric lymph node involvement in low rectal cancer: a retrospective case series

10.21203/rs.3.rs-33839/v4 ◽

2020 ◽

Author(s):

Peng Li ◽

Zhichun Zhang ◽

Yuanda Zhou ◽

Qingsheng Zeng ◽

Xipeng Zhang ◽

...

Keyword(s):

Rectal Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Dissection ◽

Low Rectal Cancer ◽

Lateral Lymph Node Dissection ◽

Node Dissection ◽

Mesenteric Lymph Nodes ◽

Lateral Lymph Node ◽

Mesenteric Lymph

Abstract Purpose The aim of this study is to examine the pattern of lymph node metastasis (lateral vs. mesenteric lymph nodes) in low rectal cancer.Methods This retrospective analysis included all patients undergoing laparoscopic total mesorectal excision plus lateral lymph node dissection for advanced low rectal cancer (up to 8 cm from the anal verge) during a period from July 1, 2017 to August 31, 2019 at the Department of Colorectal Surgery, Tianjin Union Medical Center. The decision to conduct lateral lymph node dissection was based on positive findings in preoperative imaging assessments.Results A total of 42 patients were included in data analysis. Surgery was successfully completed as planned, without conversion to open surgery in any case. A minimumal of 10 mesenteric lymph nodes and 1 lateral lymph node on each side were dissected in all patients. Pathologic examination of resected specimens showed no metastasis to either mesenteric or lateral lymph nodes in 7 (16.7%) case, metastasis to both mesenteric and lateral lymph nodes in 26 (61.9%) cases, metastasis to mesenteric but not lateral lymph nodes in 4 (9.5%) cases, and metastasis to lateral but not mesenteric lymph nodes in 5 (11.9%) cases (n=2 in the obturator region; n=3 in the iliac artery region).Conclusion A clinically significant proportion of low rectal cancer patients have metastasis to lateral lymph nodes without involvement of mesenteric lymph nodes. More carefully planned prospective studies are needed to verify this preliminary finding.

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