He's happy because his gut flora is happy!

He’s happy because his gut flora is happy!


Continuing with my coverage of regulatory tight-junction proteins and gut-barrier function, today I want to examine the role of a particular member of our beneficial gut flora community.

A 2008 study examined which of the following gut bacteria contributed the most to gut-barrier function (1):

  • Bifidobacterium breve
  • Bifidobacterium infantis
  • Bifidobacterium longum
  • Lactobacillus acidophilus
  • Lactobacillus delbrueckii Bulgaricus
  • Lactobacillus casei
  • Lactobacillus plantarum
  • Streptococcus salivarius Thermophilus

Of these strains, Bifidobacterium infantis (B. infantis), Bifidobacterium breve, Lactobacillus plantarum, Lactobacillus acidophilus and Lactobacillus casei ranked one through five in that order. As the clear champ, these researchers decided to study just how effective B. infantis was at strengthening gut-barrier defenses.


Courtesy: Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function

Courtesy: Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function


The upper-left graph illustrates the resistance of gut-epithelial cells to permeability when treated with B. infantis in a cultured medium (Bi-CM). This was assessed by the use of a EVOM voltohmmeter.

This handy little lab gadget measures TEER, or trans-epithelial electrical resistance. Note how B. infantis increases barrier function after six hours and keeps working for at least 24-hours.

The upper-right-hand graph displays resistance to paracellular transport of mannitol. Recall that this macromolecule should never be able to cross a healthy gut wall. Mirroring what was observed in the resistance test, decreased permeability to this molecule is evident for a full 24-hours.

In the bottom graph, resistance is tracked over a 40-hour period with peak levels reached between hours 24 and 40. The lowest dashed line illustrates what happens when adding a substance (PD98059) that inhibits the expression of mitogen-activated protein kinases or MAPKs. I’ll explain this effect in a bit.


Here we see how B. infantis impacts various tight-junction proteins. With the exception of claudin-2 which increases intestinal permeability, higher is better.

If we concentrate on what happens at 6- and 24-hours, we see that B. infantis has dramatic effects on the expression of these proteins thereby reducing intestinal permeability. And decreased permeability always translates into reduced endotoxemia, chronic immune activation, autoimmune disease and cortisol release.


cytokines b infantis


This illustrates the measure of resistance when gut cells are challenged by two inflammatory cytokines: tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ). Both cytokines increase intestinal permeability by their negative impact on tight-junction proteins.

Both TNF-α and IFN-γ are up-regulated in patients with Crohn’s disease and other inflammatory bowel disorders. (2) (3)

The first bar represents germ-free control cells and serves as a baseline measurement. The second bar notes the dramatic fall in resistance (increase in permeability) when gut cells are in contact with TNF-α. No surprise here.

However, as seen in the third bar, add B. infantis and it cancels out the increase in gut leakiness caused by TNF-α.

Moving on to the fourth bar, the addition of PD98059, the MAPK inhibitor I mentioned above, cancels out the advantageous effect of B. infantis and confirms that this pathway is how this gut microbe influences tight junctions.

The fifth bar demonstrates what IFN-γ does to tight junctions, mimicking what was seen in the presence of TNF-α. The sixth bar, the one that looks like a skyscraper, illustrates how B. infantis more than compensates for the effects of IFN-γ.

The last bar once again demonstrates how adding an inhibitor to MAPK reduces the ability of B. infantis to affect tight junctions for the better.




This fluorescent scan shows the effects on two tight-junction proteins, claudin-1 and occludin, when subjected to inflammatory cytokines with or without B. infantis. Note the third and fifth columns showing what happens to these junction proteins in the presence of TNF-α and IFN-γ.

These cytokines disorganize these structures by moving proteins from the membrane into the cell’s interior or cytoplasm. Add B. infantis and these cell membranes normalize.

By the way, gluten’s, or to be more precise gliadin’s, effect on zonulin signaling increases the expression of these cytokines:

“Based on these data…it is conceivable to hypothesize the following sequence of events: after oral ingestion, gliadin interacts with the small intestinal mucosa causing IL-8 [interleukin 8] release from enterocytes…, so leading to immediate recruitment of neutrophils in the lamina propria. At the same time, gliadin-permeating peptides…initiate intestinal permeability through a MyD88- dependent release of zonulin…that enables paracellular translocation of gliadin and its subsequent interaction with macrophages…within the intestinal submucosa. This interaction initiates signaling through a MyD88- dependent but TLR4- and TLR2-independent pathway, resulting in the establishment of a proinflammmatory…cytokine milieu that results in mononuclear cell infiltration into the submucosa. The persistent presence of inflammatory mediators such as tumor necrosis factor (TNF)-α and and interferon (IFN-γ) causes further increase in permeability across the endothelial and epithelial layers, suggesting that the initial breach of the intestinal barrier function caused by zonulin can be perpetuated by the inflammatory process after the access of gliadin to the submucosa.” [Emphasis mine]

Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer (4)

While there is no proof that B. infantis can overcome celiac disease, I wouldn’t eat too much wheat without healthy colonies of B. infantis if I were you.

So how exactly is B. infantis doing this?

By acting on mitogen-activated protein kinases or MAPKs. And what, pray tell, are MAPKs?

From Wikipedia we learn:

“MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens [cell division], osmotic stress [rapid changes in water coming in or out of a cell], heat shock and proinflammatory cytokines. They regulate proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis [cell death]- among many others. MAP kinases are found in eukaryotes [cells containing a nucleus] only, but they are fairly diverse and encountered in all animals, fungi and plants, and even in an array of unicellular eukaryotes.”

In other words, if you can influence MAPKs, you can, at a minimum, influence how rapidly cells grow, divide, die and how their DNA is expressed. I don’t know a cellular biologist living today who wouldn’t want to master that power.

Three distinct groups of protein kinases have been identified in warm-blooded animals, with one, extracellular signal-regulated kinase (ERK) having direct effects on intestinal barrier function. Beneficial gut flora, but B. infantis in particular, is extremely effective in activating this particular kinase group through a process known as phosphorylation resulting in up-regulation of tight junction expression and decrease in intestinal permeability.

Ain’t that just “friggen” cool? (Yes, that’s my inner nerd speaking:)

OK, let’s see what happens when B. infantis is administered to mice bred to lack interleukin 10 (IL-10). IL-10 is an anti-inflammatory cytokine that works in opposition to inflammatory cytokines like TNF-α and interleukin 6 (IL-6). Consider it the ying to the yang of those cytokines.

Mice bred to be deficient in IL-10 develop inflammation of the colon (colitis) between six to eight weeks of age, and experience increased intestinal permeability as a result. Because of this, inflammatory immune responses run amok in these mice.




Here we see illustrated levels of intestinal permeability in IL-10 deficient mice with or without supplementation of B. infantis. Permeability as measured by both the presence of mannitol in urine (A) and cell resistance (B) is dramatically reduced with the addition of this gut bacteria.

As the researches note:

“Mice receiving BiCM treatment showed enhanced weight gain, decreased colonic weight, and decreased colon weight-to- length ratio compared with control animals. This was associated with a significant attenuation of histological inflammation and a significantly reduced mannitol flux compared with controls.”

What’s true for these mice is true for us. Unfortunately, some of the first bacteria to be devastated as a result of antibiotic use are bifidobacteria.

Populations of bifidobacteria in infants and children are particularly vulnerable to these drugs. In infants, the health of these bacterial communities are also affected by the mode of delivery, the state of the mother’s gut flora at birth and how that infant is subsequently fed. (5)

Sadly, many children carry their gut dysbiosis well into adulthood. Dietary and lifestyle factors, as well as repeated courses of antibiotics, continue to make a bad situation worse.

Healing and sealing a gut is going to be very difficult to accomplish without this extremely important member of the human microbiome. Replenishing this bacteria and nurturing its growth are both essential for those battling gut dysbiosis.

Bifidobacteria like B. infantis love to ferment certain soluble fibers (prebiotics) so be sure to include these either as part of your diet or as a supplement. (6) And any probiotic you take should most definitely have B. infantis as part of its formulation.


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