Bacterial translocation is the invasion of indigenous intestinal bacteria through the gut mucosa to

normally sterile tissues and the internal organs. Sometimes instead of bacteria, inflammatory
compounds are responsible for clinical symptoms as in systemic inflammatory response
syndrome (SIRS). The difference between sepsis and SIRS is that pathogenic bacteria are
isolated from patients with sepsis but not with those of SIRS. Bacterial translocation occurs more
frequently in patients with intestinal obstruction and in immunocompromised patients and is the
cause of subsequent sepsis. Factors that can trigger bacterial translocation from the gut are host
immune deficiencies and immunosuppression, disturbances in normal ecological balance of gut,
mucosal barrier permeability, obstructive jaundice, stress, etc. Bacterial translocation occurs
through the transcellular and the paracellular pathways and can be measured both directly by
culture of mesenteric lymph nodes and indirectly by using labeled bacteria, peripheral blood
culture, detection of microbial DNA or endotoxin and urinary excretion of non-metabolisable
sugars. Bacterial translocation may be a normal phenomenon occurring on frequent basis in
healthy individuals without any deleterious consequences. But when the immune system is
challenged extensively, it breaks down and results in septic complications at different sites away
from the main focus. The factors released from the gut and carried in the mesenteric lymphatics
but not in the portal blood are enough to cause multi-organ failure. Thus, bacterial translocation
may be a promoter of sepsis but not the initiator. This paper reviews literature on the
translocation of gut flora and its role in causing sepsis.

Keywords: Bacterial translocation, gut microflora, immunosuppression, multi-organ failure,

sepsis

How to cite this article:

Vaishnavi C. Translocation of gut flora and its role in sepsis. Indian J Med Microbiol
2013;31:334-42

How to cite this URL:

Vaishnavi C. Translocation of gut flora and its role in sepsis. Indian J Med Microbiol [serial
online] 2013 [cited 2014 Aug 10];31:334-42. Available
from: http://www.ijmm.org/text.asp?2013/31/4/334/118870

~ Introduction

The human gastrointestinal tract is inhabited by a plethora of bacteria belonging to over a 1000
different species [1] comprising of obligate anaerobes (95%) and facultative anaerobes (5%).
Obligate anaerobes include Bifidobacterium, Clostridium, Eubacterium, Bacteroides,
Fusobacterium, Peptococcus and Peptostreptococcus. The facultative anaerobes include
Lactobacillus, Bacillus, Streptococcus, Staphylococcus, Escherichia More Details coli, Klebsiella
and Pseudomonas aeruginosa.[2] Bifidobacteria are the predominant cultivable bacteria in 80%
of infants and 25% adults.[3] The resident flora comprises of distinct organisms that are
constantly present in a given region of the intestine at a particular age. The transient flora
consists of non-pathogenic or potentially pathogenic organisms that colonise the intestine for
different periods of time.[4] Commensal bacteria rarely cause local or systemic disease despite
their presence in extremely high numbers. A unicellular epithelial layer on the intestinal mucosa
prevents these micro-organisms from migrating to extra-intestinal sites.

The gut microflora has a great role to play. They directly activate the development and
differentiation of intestinal epithelium and play an important role in maintaining the integrity of
the enterocytes.[2] They contribute to nutrition by producing several enzymes for digestion as
well as for mucous secretion [2] and take part in synthesis of vitamins and absorption of
minerals.[5] The gut bacterial flora maintains an immunologically balanced inflammatory
response [2] by modulating metabolic and immunologic processes and protecting against
colonisation by invasive pathogens.[6] This paper reviews literature on the translocation of gut
flora and its role in sepsis. Literature searches were made through PubMed, Medline, Medscape
News and own publications.

History

For centuries scientists and investigators wondered how a single layer of intestinal epithelial
cells could defend against the hostile lumen environment and the sterile bloodstream. In the later
part of the 19 th century realization dawned upon them that peritonitis could result from the
passage of bacteria from organs adjacent to the peritoneal cavity and the "gut origin of sepsis"
became a theory interesting the clinicians. During that time, two investigators [7],[8] hypothesised
that living bacteria could pass through the intact gut wall in vivo. Much later on Schweinburg et
al.,[9] detected viable bacteria in the peritoneal cavity of experimental model of haemorrhagic
shock in dogs. Next, another group of workers [10] demonstrated in humans that bacteria could
migrate from the gastrointestinal tract into the portal circulation even when there was no
infective process. The passage of living bacteria through the intestinal wall was believed to lead
to bacterial peritonitis.[8],[11]

Bacterial translocation

Bacterial translocation is the invasion of indigenous intestinal bacteria through the gut mucosa to
normally sterile tissues such as the mesenteric lymph nodes (MLN) and the internal organs. [12]
Sometimes instead of bacteria, inflammatory compounds are responsible for clinical symptoms
as in systemic inflammatory response syndrome (SIRS). The difference between sepsis and SIRS
is that pathogenic bacteria are isolated from patients with sepsis but not with those of SIRS.
Thus, in SIRS the intestine becomes a cytokine-generating organ due to ischaemia as a result of
trauma, burns, obstructive gastrointestinal injury, haemorrhagic shock or sepsis.[13]

The definition of bacterial translocation was therefore broadened further in relation to intestinal
permeability, to include passage of antigens or endotoxins from the gut lumen into the
circulation causing systemic inflammation and distant organ injury. Illness creates a hostile
environment in the gut and alters the microflora favouring the growth of pathogens that promote
bacterial translocation. Portal hypertension leads to intestinal submucosal oedema which disrupts
the protective integrity of mucosal barrier. All these leads to an imbalance of gut microflora
favouring the overpopulation of enteric Gram-negative bacteria, and an increase in endotoxin-
mediated mucosal injury leading to impaired mucosal defences. [14]

Evidence for bacterial translocation in humans

Though gut translocation of bacteria has been demonstrated in both animal and human studies,
[15],[16],[17]
its existence and importance in humans are difficult to prove. O'Boyle et al.,[16]
reported bacterial translocation from gut to MLN occurring in 15% of 448 surgical patients.
They reported a significant increase (45%) in postoperative sepsis in patients with bacterial
translocation compared to those with negative MLN cultures (19%) with organisms being similar
in the clinical infections and those isolated in the MLN. On the other hand, most of the patients
with bacterial translocation to MLN showed no clinical infectious complications, thereby
suggesting that bacterial translocation could be a natural condition in some cases and not
clinically significant when the immune system is functional. Marshal et al.,[18] demonstrated that
>90% of patients in the intensive care unit (ICU), who had infection had at least a single episode
of infection with the same organisms as seen in the upper gastrointestinal tract. In human studies,
nosocomial infections were correlated with indigenous gut bacteria isolated in blood cultures and
surgical wounds [18],[19] and also in ascites of cirrhotic patients who had spontaneous bacterial
peritonitis.[20] Thus, increased circumstantial evidence has accumulated regarding bacterial
translocation in humans [21] with a prevalence of about 15% in elective surgical patients.[22] Even
though mortality is not always the outcome, bacterial translocation occurs more frequently in
patients with intestinal obstruction and in immunocompromised patients and is the cause of
subsequent sepsis. A few studies have demonstrated bacterial translocation by detection of
endotoxin [23] or by bacterial culture of portal or systemic blood. [24],[25]

A prospective study was conducted where cultures of nasogastric aspirates from 279 surgical
patients were compared with those from MLN collected at laparotomy and cultures from
subsequent septic complications.[22] The nasogastric aspirates in 31% of the patients were sterile.
Among the positive cultures, the commonly identified organisms were E. coli (20%) and candida
(54%). Multiple organisms were recovered from 39% of patients most of whom were aged over
70 years, those undergoing non-elective surgery and those requiring proximal gastrointestinal
surgery. Bacterial translocation occurred in 21% of patients and was more common in patients
with multiple organisms in their nasogastric aspirates. However, no fungal translocation was
noted. E. coli was commonly isolated from the lymph nodes (48%) and the septic foci (53%).
Simultaneous identification of an identical genus was demonstrated in nasogastric aspirate and
septic focus in 30% patients, in nasogastric aspirate and lymph node in 31% and lymph node and
septic focus in 45%. The authors concluded that proximal gut colonisation was associated with
both increased bacterial translocation and septic morbidity.

Factors for bacterial translocation

There are several factors that can trigger bacterial translocation from the gut, yet all of them have
not been fully determined. Some important factors responsible for bacterial translocation are as
hereunder.
Host immune deficiencies and immunosuppression: Immune deficiencies and
immunosuppression of the host is probably one of the most important factors for bacterial
translocation. Immune carpeting by secretory IgA, mucous, a glycocalyx brush border etc.,
represent an anatomical barrier that separates the luminal contents of the gut from the internal
milieu. When a person is immunocompromised due to a severe illness, the normal defence
mechanism of the gut barrier fails to stop bacterial translocation. Leukaemia has been found to
be associated with increased bacterial translocation to blood. O Boyle et al., [16] showed an
association between multi-organism colonies and an increasing incidence of postoperative sepsis
compatible with speculative mechanism of translocation. They suggested that it might probably
be a manifestation of immunosuppression, as greatest translocation was seen in elderly patients.
Bacterial translocation also gets promoted by immunodeficiency agents like immunosuppressive
drugs, lymphoma, burn injuries, endotoxic shock and haemorrhagic shock.

Disturbances in normal ecological balance of gut: Disturbance in the normal gut flora is also one
of the major pathogenic factors responsible for bacterial translocation. The stomach is usually
sterile. The upper gut may have 10 6 -10 8 bacteria/ml and the colon up to 10 12 bacteria/ml. The
gut flora is manipulated by various factors like diet, gastric acid, gastric and luminal secretions,
bile salts, lysozyme, secretory IgA antibodies, antibacterial drugs, bacterial interactions and gut
peristalsis.[4] Despite their high concentration, obligate anaerobes are rarely known to translocate,
indicating that increased population of a particular organism is not the major criterion for
bacterial translocation. Different pathogenic bacteria with particular virulence factors contribute
to natural disturbances and displacement of the normal flora thereby leading to infection.
Promotion of bacterial translocation by overgrowth of intestinal bacteria is due to oral
antibiotics, endotoxic shock, starvation, protein malnutrition, parenteral nutrition, bowel
obstruction, etc., Colonisation resistance by indigenous gut flora safeguards the host from
colonisation by exogenous pathogens. Disruption of indigenous flora by prolonged critical care
therapy leads to imbalance between the host and the gut flora [26] due to antibiotics. Other factors
that may predispose the disturbance of gut flora are gastroprotectant agents, vasoactive agents,
opioids and parenteral nutrition.

Mucosal barrier permeability: The first line of defence against bacterial invasion is the mucous
coat overlying the epithelia. It contains mucin and antimicrobial peptides. Toll-like receptors on
the luminal surface of enterocytes sense danger and activate host defences. Once the pathogens
pass the mucous and epithelial barriers, they are phagocytosed by submucosal macrophages. [27]
Hypoperfusion leads to the movement of blood away from splanchnic circulation toward more
vital organs. Consequently there is reperfusion injury of villi, release of pro-inflammatory
factors, mucosal disruption, increased intestinal permeability and bacterial translocation. The
integrity of gut mucosa is needed for an adequate delivery of oxygen and nutrients. When there
is disturbance in the microcirculation an increase in oxygen radicals generated from
macrophages and leucocytes [28] may lead to increased mucosal permeability. Bacterial
translocation can occur when there are breaches in the mucosal barrier as during ulceration.
However, physical integrity is maintained by a rapid turnover and migration of specialized cells
to the site of injury.[29] Factors that can promote bacterial translocation by increasing intestinal
permeability are ingredient such as castor oil and conditions of endotoxic shock, haemorrhagic
shock and burn injuries. It is also likely that the gut barrier gets broken down by other factors
which may give rise to SIRS.[13]
Obstructive jaundice: Obstructive jaundice impairs epithelial barrier permeability by
immunological disturbance and by inhibitory effect of bile on bacterial invasion of
enterocytes.[30] In obstructive jaundice, there is diminishing or ceasing of bile flow to the gut
resulting in failure of the reticuloendothelial system, immunosuppression, as well as architectural
and functional changes in intestinal mucosa. [31] The deficiency of bile within gastrointestinal
tract allows intestinal bacterial overgrowth of Gram-negative bacteria, leading to bacterial
translocation.

Stress: Psychosocial stress such as immobilisation induces physiological abnormalities in the gut.
Strong colonic inflammatory response and alteration of colonic epithelial barrier leads to
increased mucosal permeability [32] and thereby bacterial translocation.

Miscellaneous factors: Factors like radiation, intestinal peristalsis and various drugs can
influence bacterial translocation. [22] Chemotherapeutic and immunosuppressive agents, non-
steroidal anti-inflammatory drugs, as well as certain antibiotics increase the bacterial
translocation. [22] Other factors that can affect the mucosal barrier and increase the permeability
include over-production of nitric oxide, [33],[34] interleukin-6 [35] alcohol, endotoxins [10] and
coliforms such as E. coli and K. pneumonia. [36]

However, apart from bacterial translocation there might still be many more factors that could
play a role in septic morbidity inclusive of factors related to colonisation of the small intestine.
[37],[38]

Pathways of gastrointestinal permeability

The components of the epithelial barrier as visualized through electron microscopy are from the
luminal aspect towards the external surface (i) internal water lining, epithelial surface layer
composed of phospholipids and mucous coat, the epithelial cells, sub-epithelial connective tissue
and the capillary endothelium. [39] At the junction between epithelial cells, closest to the luminal
surface lies the tight junction and underneath is the adherens junction. [40] The tight junctions are
composed mainly of proteins such as claudins and occludins and hold the epithelial cells
together. The function of the gut barrier depends on the gut flora, the mucous epithelium, the
secretory IgA and the immune cells.

Acidosis of the mucosa occurs by reduction in blood flow that decreases tissue oxygenation and
consequent epithelial cell injury. This leads to increased mucosal permeability mediated by
activation of neutrophils and free oxygen radicals, which disrupts the cytoskeleton of the
mucosa. [41],[42],[43],[44] However in normal conditions bacteria passing through the intestinal
epithelia are destroyed by phagocytes before reaching the blood circulation, as gut-associated
lymphoid tissue plays an important role in controlling bacterial translocation. When translocated
bacteria and toxic compounds get drained by the mesenteric lymphatic system, they get trapped
in the intestinal lymph nodes causing an inflammatory response.

Bacterial translocation occurs through the transcellular and the paracellular pathways, which may
occur singly or in combination.
Transcellular pathway: Transcellular pathway is a more common method occurring through the
enterocytes and is under the control of specific enterocyte channels and membrane pumps. [22] It
involves the transportation of substances using the primary and the secondary active transport
across the intestinal epithelial cells through both the apical and the basolateral membranes.

Paracellular pathway: Epithelial tight junctions open and close all the time in response to a
variety of stimuli such as dietary conditions, humoral or neuronal signals, inflammatory
mediators and microbial stimuli. Paracellular pathway probably occurs through disruption of the
tight junctions and is affected by luminal osmolality and direct damage to the cytoskeleton of the
enterocytes composed of actin filaments and microtubules.

Similarly, there are two major routes taken by bacterial compounds like endotoxins to reach the
circulation (i) via enteric venous system to portal vein or (ii) following lymphatic enteric
drainage [Figure 1].

Figure 1: Diagrammatic depiction of pathways of gastrointestinal

permeability

Click here to view

Measurement of bacterial translocation

Bacterial translocation can be measured both directly and indirectly.

Direct methods: There are two direct methods of measuring bacterial translocation.

By culture of mesenteric lymph nodes: Bacterial translocation can be measured by identification

of intestinal bacteria in normally sterile MLN. [16],[45] For culture of MLN a lymph node from the
mesentery of the terminal ileum is excised at laparotomy and homogenized in sterile saline. The
homogenate is inoculated onto Columbia blood agar and cysteine lactose electrolyte deficient
(CLED) media and incubated aerobically at 37°C for two days. Anaerobic culture is carried out
on Wilkins-Chalgren blood agar with neomycin and Columbia blood agar and incubated
anaerobically at 37°C for five days. Isolates from culture are identified by standard
microbiological tests. [16],[45]

This method is useful only when culture of MLN provides some growth of bacteria, but not
when they are sterile, thus underestimating the real incidence of bacterial translocation.

By using labeled bacteria: Another direct method is to use radioactively labeled bacteria. Diniz et
al., [46] evaluated the translocation of 99mTc labelled E. coli to MLN, liver, spleen, lung and
serum of Wistar rats submitted to mesenteric ischaemia/reperfusion for 45 min by occlusion of
the superior mesenteric artery. The translocation of labelled bacteria to different organs and
portal serum was determined in rats reperfused for 30 min, 24 h, sham and controls, using
radioactivity count and colony forming units/g. All the organs from rats observed for 24 h after
reperfusion had significantly higher levels of radioactivity and positive cultures than did the
organs of rats reperfused for 30 min, sham and controls, except in the spleen indicating that
intestinal ischaemia/reperfusion led to bacterial translocation, mostly after 24 h of reperfusion.
This method has the advantage that even if bacteria are killed by gut associated lymphoid tissue
when they traverse the intestinal epithelial barrier [47] they can still be located.

Indirect methods: There are several indirect methods to measure bacterial translocation.

Blood culture: Indirect evidence of bacterial translocation involves the detection of intestinal
bacteria in cultures of portal or peripheral blood. [48] Aerobic and anaerobic blood culture bottles
are incubated constantly at 37°C for five days with 10ml of blood in BACTEC culture vials. All
blood cultures with positive readings are further inoculated into Columbia blood agar, chocolate
blood agar and CLED media. Isolates are identified by standard microbiological tests. [15]

Detection of microbial DNA: The detection of microbial DNA in biological fluids by polymerase
chain reaction (PCR) is another marker of measurement of bacterial translocation and has a
higher sensitivity than blood cultures. Bacterial DNA in ascites and serum is present in one-third
of patients with cirrhosis and ascites. [49] DNA is extracted from biological fluids and PCR
techniques used to amplify genes from E. coli, Bacteroides fragilis and 16SrRNA found in many
Gram-positive and Gram-negative bacteria. [50] The advantage lies in the ability to perform serial
measurements in the same patient for the prevalence of microbial DNA. Convincing evidence of
disease causation in the absence of cultivated microorganism may be had by combining PCR
results with relevant clinical information. It is also a useful tool for the detection of bacterial
translocation in patients who do not have a defined infectious focus. The challenge for PCR
screening of blood for rapid microbial identification is to understand when microbial DNA in
blood represents a true infection.

Detection of endotoxin: Endotoxin or lipopolysaccharide (LPS) is a characteristic and integral

component of the outer membrane of all Gram-negative bacteria and it induces bacterial
translocation from the gut. Portal hypertension leads to intestinal sub-mucosal oedema that
disrupts the protective integrity of mucosal barrier and results in an imbalance of gut microflora,
increased bacterial endotoxin-mediated mucosal injury and weakened mucosal defences.
Detection of endotoxin from the blood is also an indirect method to detect bacterial translocation.
[37],[51]
Endotoxins in body fluids are detected by the Limulus amoebocyte lysate assay. LPS
causes the clotting of extracts of amoebocytes of the horseshoe crab, Limulus polyphemus. Non-
specific amidase and other inhibitors in human plasma however interferes with the results.
Recently, two new quantitative endotoxin microplate assays using homogenous and
heterogenous fluorescence phage recombinant technology and recombinant horseshoe crab factor
C that removes sample inhibitory effects have become available.

Urinary excretion of non-metabolisable sugars: Another indirect method to detect bacterial

translocation is assessment of non-metabolisable sugars such as lactulose (paracellular) and
mannitol (transcellular) in the urine [52],[53] after oral administration. Increased urinary excretion
of the sugars indicates disruption in the integrity of mucosal barrier and thereby enhanced risk of
bacterial translocation.
Bacterial translocation in health and disease

Health: It has been proposed that bacterial translocation may be a normal phenomenon occurring
on frequent basis in healthy individuals without any deleterious consequences. [21] The rate of
bacterial translocation in healthy human individuals is approximately 5-10% [54] which is much
lower than that in animals where it is approximately 10-20%. [12] This physiologic event
probably allows the gastrointestinal tract to be exposed to antigens and thereby mount a local
immune response and develop a kind of tolerance. But when the immune system is challenged
extensively, it breaks down and results in septic complications.

Disease: Bacterial translocation can occur in several clinical conditions such as small bowel
bacterial overgrowth, damage to intestinal barrier and conditions of systemic
immunosuppression. [42],[55] Bacterial translocation has been identified in patients with ileus,
colorectal cancer, cirrhosis, obstructive jaundice, acute pancreatitis, abdominal surgery [56],[57],[58]
bowel transplant [59] haemorrhagic shock, heart diseases and those receiving parenteral
nutritional support. Bacterial translocation in some of the disease conditions are discussed below,
even though many of the conditions are overlapping.

In acute pancreatitis: The average mortality rate of patients with acute pancreatitis is 10-15% [60]
which increases to 30-40% in patients with severe disease. [61] The main cause of death in the
first week after the onset of acute pancreatitis is multi-organ dysfunction syndrome (MODS).
Mortality and morbidity occurring during later periods is due to sepsis. [62] Infections associated
with acute pancreatitis are related to enteric bacteria [63],[64] and may be due to bacterial
translocation from gut to necrosal region. [61] Bacterial migration may be due to direct transmural
migration to the peritoneal cavity or to retroperitoneum, or through lymphatic or haematogenous
spread to the pancreas. [65] Bacterial translocation in acute pancreatitis plays a key role in the
occurrence of infectious complications.

Bacterial overgrowth and intestinal dysmotility: The enteric bacterial population gets regulated
by the motility of small bowel. Acute pancreatitis may result in a significant delay in small
intestinal transit time [60],[66] by secretion of some gastrointestinal peptides, which leads to small
bowel bacterial overgrowth. Sympathoadrenal stimulation, elevated nitric oxide synthesis and
oxidative stress result in bacterial overgrowth. The decrease in bile acid due to cirrhosis
facilitates bacterial translocation. Local or any systemic deficiencies in the immunity result in
bacteraemia and subsequent seeding of other sites, inclusive of ascitic fluid.

In cirrhosis: Patients with cirrhosis have a decreased small bowel motility, hypochlorhydria and
reduced luminal IgA secretion [67] leading to small bowel overgrowth of bacteria. [68] Cirrhotic
patients have increased susceptibility to bacteraemia and spontaneous bacterial peritonitis (SBP)
[69]
due to decreased defensive mechanisms. The majority SBP cases are caused by Gram-
negative bacteria which selectively cross the intestinal barrier. They gain access to the MLN
from where they reach the blood circulation. Haemodynamic changes brought about by cirrhosis
lead to a number of detrimental effects on enteric motility, permeability and microflora. An
overactive sympathetic nervous system slows down the gut motility thereby facilitating bacterial
stasis, translocation and overgrowth. Anaerobic flora, though high in population, are rarely
involved in SBP, probably due to their inability to translocate or due to high availability of
oxygen in the colonic wall, which is detrimental to their survival. Adherent and virulent strains
of E. coli translocate the mucosal wall because of their ability to fight against the natural host
defence mechanism. [70]

In patients with severe trauma and burns: Urinary excretion of lactulose and mannitol was found
to be increased in patients with severe trauma [71] and burn patients with infection, [72] thereby
indicating bacterial translocation from gut.

In patients with nutritional support: It is believed that total parenteral nutrition (TPN) is
associated with mucosal atrophy and increased intestinal permeability which reflect damage to
the gut barrier due to absence of enteral nutrition. This could predispose to bacterial translocation
and could be one of the factors for increased rates of septic complications found in studies
investigating TPN. [73] However there is no evidence suggesting the association of short term
TPN with villus atrophy or significant changes in intestinal permeability [17] or alterations in gut
permeability or mucosal architecture predisposing to increased prevalence of bacterial
translocation. Thus, there is no concrete evidence that septic complication is increased in patients
receiving TPN as against those with enteral nutrition. [59],[74]

Multi-organ failure

The gut is the largest immune organ in the body and the major source of factors that trigger the
acute septic response and organ failure in patients sustaining major trauma, burns or shock. Live
bacteria or their products or both, cross the intestinal barrier where they directly cause infection
or excite the immune system. Consequently there is a massive inflammatory reaction resulting in
diffuse organ damage and eventually organ failure and death. [75] The concept of gut-induced
sepsis was that during shock or stress conditions there is decreased blood flow to the intestines,
causing gut injury that makes it leaky. This would allow bacteria and endotoxin to enter the
circulation leading to sepsis and subsequently MODS. The factors that cause gut mucosal injury
and promote bacterial translocation also trigger the gut to produce biologically active substances
that injure the tissues. The factors carried in the mesenteric lymphatics but not in the portal blood
are enough to cause MODS. The rate of positive culture in diseases such as MODS and intestinal
ischaemia is 16-40%. [12]

There is much circumstantial evidence that the gut is the reservoir of organisms responsible for
sepsis leading to multi-organ failure. When critically ill patients receive only TPN without the
enteral feeding for long periods, besides antibiotics, antacids and narcotics, alteration of
gastrointestinal flora occurs which may lead to bacterial translocation. In acute respiratory
disorder syndrome occurring in septic patients the lungs are the first organ to receive lymph
drainage from the gut through the thoracic duct draining into the systemic circulation. Thus
bacterial translocation might also be responsible for lung injury. [76] In severe SIRS, the state of
immune suppression may lead to more severe infection. MODS have reached epidemic
proportions and is responsible for 50-80% of all mortality in surgical ICU. It is believed that gut-
induced sepsis in critically ill patients is due to gut-barrier failure allowing bacteria and bacterial
products to enter the systemic circulation [77] resulting in systemic sepsis and MODS.
[11],[43],[78],[79]
Selective decontamination of the gut appears to reduce infections in a subset of ICU
patients. [80]

Bacterial sepsis also remains a significant cause of paediatric morbidity and mortality. Modes of
blood stream infections are bacterial translocation across the epithelial mucosa as in the lungs,
gastrointestinal tract, urinary tract, genital tract, wounds on the skin, catheters and medical
devices. [81] Bacterial translocation across gastrointestinal tract is the most important among
these factors in critically ill children. [18] Gut permeability is fostered in premature infants due to
reduced mucosal barrier function. [82] In low birth-weight infants the intestinal macrophages are
dysfunctional. [83],[84] Pierro et al.,[85] observed that in infants receiving parenteral nutrition,
septicaemia may be gut-related phenomenon.

Prevention of bacterial translocation

It has been suggested that introduction of foods that sustain the growth of intestinal
microorganisms might prevent bacterial translocation. [86] Breast-fed infants have proliferation of
Bifidobacteria and Lactobacilli whereas formula-fed infants have more Enterococci and
enterobacteria. Certain nutrients like glutamine, arginine, prebiotics, probiotics and anti-oxidants
have specific beneficial effects on the gut function. Glutamine is the preferred fuel for the
stability of the enterocytes. Prebiotics are non-digestible food substances (i.e. inulin,
oligosaccharides) that beneficially affect the host by selectively stimulating the growth and
activity of some bacteria in the colon. Probiotics are microorganisms (e.g. Lactobacillus) which
when ingested offer potential health benefits to host, and are often concurrently administered
with prebiotics. Probiotics have effect only in conditions like necrotizing enterocolitis in
neonatal infants. Ciprofloxacin and ursodeoxycholic acid have a synergic effect on prevention of
bacterial translocation in obstructive jaundice as observed in animal study. [87] Drugs such as
cisapride, propranolol, sucralfate, bile salts and prostaglandin analogues have been shown to
decrease bacterial translocation. [22]

~ Conclusion

Increased evidence has accumulated that in the immunocompromised persons bacterial

translocation occurs across the intestinal barrier leading to sepsis at different sites away from the
main focus. In the majority of non-immunocompromised persons, though translocation does
occur, the integrity of the barrier is maintained, causing no damage to the host. However, apart
from bacterial translocation there might still be many more factors such as those related to
colonisation of the small intestine that could play a role in septic morbidity. Thus bacterial
translocation may be a promoter of sepsis and not the initiator.

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