Lactobacillus Casei

Lactobacillus casei is a bacterial species and probiotic supplement in the Lactobacillus family, and a popular strain of this bacteria is referred to as Shirota (Lactobacillus casei Shirota)^[1] and as its family name suggests, it is a lactic acid producing bacteria via fermentation and normally occurs in the human intestinal tract.^[2]

Obesity appears to be associated with increase lipopolysaccharide (LPS) appearance in serum, which is thought to be from a combination of increased intestinal permeability and a heightened ratio of gram negative:positive bacteria.^[3] LPS, via signalling through the TLR4 receptor (on immune cells), can promote symptoms of metabolic syndrome and usually is seen to promote obesity and insulin resistance.^[4][5][6][7] Excessive chronic elevations of LPS are thought to play a contributing role in metabolic syndrome.

Lipopolysaccharide binding protein (LBP) is a 60kDa protein that facilitates signalling by transporting LPS to the CD14 receptor, a coreceptor that responds to LPS as well as TLR4 (and MD2); concentrations of LBP correlate with LPS and it is sometimes used as a biomarker^[8][9] and LBP has been further shown in humans to positively correlate with both obesity and insulin resistance.^[8][9][10]

Lipopolysaccharide (LPS) and its binding protein (LPS binding protein or LBP) are increased in the blood of obese persons relative to lean controls, and as they are produced by gram negative bacteria in the gut it is thought that this increase is due to increased gut permeability. LPS has proinflammatory mechanisms to promote obesity and insulin resistance

Endurance athletes supplemented with L. casei Shirota (6.5x10⁹ CFU delivered via fermented milk) daily for 16 weeks while training during the winter months experienced no change in white blood cell count or subfraction when compared to placebo.^[11] Another study using L. casei strain DN-114 001 (dose not specified) for close to 4 weeks in military cadets undergoing extreme training also found no significant effects on immune parameters, but noted a trend to blunt the increase in white blood cells at the end of training in the probiotics group compared to placebo.^[12]

Supplementation with L. casei Shirota (6.5x10⁹ CFU delivered via fermented milk) for 16 weeks in endurance athletes significantly increased salivary IgA compared to those supplemented with placebo. This effect was seen 8 weeks after supplementation started, and not before. However, neither plasma IgA nor salivary or plasma IgA or IgM was affected.^[11] Another study in military cadets supplemented with an unspecified dose of L. casei strain DN-114 001 while undergoing intense training saw a trend toward abolishing training-induced declines in salivary IgA.^[12]

L. casei Shirota has been noted to, when tested in vitro, induce release of GM-CSF, IL-12 and IFN-γ to a relatively higher degree than other tested strains.^[13]

When assessing IL-17, l. casei shirota (9.2-10.1x10⁹ CFU) over 63 days in rats was noted to not exacerbate symptoms of experimental autoimmune encephalomyelitis although it was also without benefit,^[14][15] this suspicion arising from thoughts that IL-17 plays a pathological role^[16] and l. casei shirota has been noted to cause a transient increase in serum IL-17 after a week of 0.6-1.2x10⁹ CFU, which was no longer present after 12 days.^[15]

L. casei shirota has also been noted to preserve IL-10 concentrations in serum during experimental autoimmune encephalomyelitis (desipte not altering synthesis rates in splenic cells^[15]) at an oral intake of 0.6-1.2x10⁹ CFU daily, where a decrease may occur with no probiotic treatment.^[15]

Supplementation with L. casei Shirota (6.5x10⁹ CFU delivered via fermented milk) for 16 weeks in endurance athletes did not affect levels of interleukins 1β, 2, 4, 6, 8, or 10 in comparison with placebo.^[11]

Supplemental Lactobacillus casei Shirota (65mL of 10⁸/mL CFU) to people with metabolic syndrome does not appear to significantly alter receptors expresses on neutrophils (TLR2,4, and 9) although it appeared that this study had significant differences in soluble CD14 expression (higher in control at baseline) which were abolished with treatment.^[1] Another study involving an unreported dose of L. casei strain DN-114 001 for close to 4 weeks during intense training by military cadets noted a statistically insignificant trend in the supplemented group in blunting a rise in neutrophils induced by the training.^[12]

L. casei Shirota has been noted to, when tested in vitro, cause activation of NK cells with similar potency to some other probiotics (including two bifidobacterium strains).^[13]

In mice under experimental autoimmune encephalomyelitis, oral intake of l. casei shirota has been noted to increase CD4⁺CD25⁺ Treg cell populations (as a ratio) with a mild decrease in CD8⁺ T cells after 12 days of 0.6-1.2x10⁹ CFU.^[15]

Endurance athletes supplemented with L. casei Shirota (6.5x10⁹ CFU delivered via fermented milk) daily for 16 weeks while training during the winter months experienced a lower prevalence (36% lower) of upper respiratory tract infection (URTI) symptoms lasting one week or more compared to similar athletes given placebo. The number of average URTI bouts was also halved in the supplemented group. However, the duration and severity of URTI symptoms was not affected by L. casei Shirota supplementation. The authors of the study believe that elevated salivary IgA may have played a role in the reduced prevalence. ^[11]

Another study using L. casei strain DN-114 001 (dose not specified) for close to 4 weeks in military cadets undergoing extreme training found no significant effects on rate or severity of respiratory infections overall. A statistically insignificant higher incidence of nasal symptoms occurred in the supplemented group and lower incidence of symptoms occurred throughout the rest of respiratory tract (again statistically insignificant). The authors argue that this may indicate that the probiotics helped confine respiratory infections to the nasal area.^[12]

One study has found that L. casei supplementation may lessen the chance of upper respiratory tract infection symptoms while training during the winter months. Length and severity of symptoms was not affected, however. Another study in military cadets found no overall effect, though.

Male bodybuilders supplemented with a multi-strain probiotic capsule that included Lactobacillus casei along with L. acidophilus, L. bulgaricus, B. breve, B. longum, and S. thermophilus for 30 days saw significantly higher T4 levels of 3.4 μg/dL over placebo and lower thyroid stimulating hormone. T3 levels were not different between groups. It is unclear if this effect can be traced back to L. casei specifically, however, due to the inclusion of multiple strains of bacteria in the supplement.^[17]

Metabolic syndrome and its comorbidity of insulin resistance are associated with increased permeability of the intestinal wall to bacteria^[18] and increased serum lipopolysaccharide (LPS) and its binding protein, two biomarkers of endotoxemia^[4] which have been confirmed to be elevated in obese humans (with metabolic syndrome) relative to healthy lean controls.^[1]

Although it is unknown what causes the increase in gut permeability, the increased ratio of gram negative:positive bacteria in the gut is thought to cause an increase in LPS (only exists in gram negative bacteria) which reaches serum;^[4] this ratio appears to be increased in rodents fed a high fat diet with subsequent obesity.^[5]

Supplemental Lactobacillus casei to rats is known to reduce (improve) intestinal permeability^[19][20] and mice that are fed Lactobacillus casei Shirota at 0.05% of the diet for 4 weeks are able to reverse a high-fat diet induced insulin resistance without affecting body weight.^[21] When tested in humans, 65mL of a solution with 10⁸ colonies per mL has failed to improve intestinal permeability over 3 months (thought to be due to too short a time frame or underdosing).^[1]

The lactobacillus species of bacteria appears to frequently colonize vaginal mucosa (mostly the species gasseri, jensenii, iners, and crispatus^[22][23]), of which casei is present in some samples.^[24] A vaginal state characterized by a deficiency of lactobacillus bacteri (in general rather than a specific strain) appears to be associated with increased risk for bacterial vaginosis^[25] and may promote the transmission of sexually transmitted infections (STIs) relative to a sufficient state.^[26][27][24]

Lactobacillus casei is one of the many species present in vaginal mucosa, but the relevance of this information to oral supplementation of the bacteria is not known