What is HT-PS23? (HT L. paracasei PS23)

In addition to the Bened Life flagship strain L. plantarum PS128, Neuralli Mood introduces a new gut-brain strain into our line-up: HT-PS23. 

To learn more about what HT-PS23 is, why it’s in Neuralli Mood, and what it can mean to your mental health, we sat down with Bened Life Chief Science Officer, Noelle Patno, PhD.

The following questions and answers have been edited for clarity.

First of all, what does “HT-PS23” mean?

Dr. Patno: 

HT-PS23 is shorthand for “heat-treated” L. paracasei PS23. PS23 is a specific strain of the bacterial species L. paracasei. L. paracasei is often found in the gut microbiota of humans and animals. While it shares some properties with other strains of L. paracasei, its probiotic (PS23) and postbiotic (HT-PS23) forms have both been uniquely studied for gut-brain and gut-muscle effects. 

What exactly is a postbiotic?

Dr. Patno:

Heat treatment is what makes HT-PS23 a postbiotic. The heat treatment process uses a high enough temperature for a long enough time that no live bacteria are present. What makes HT-PS23 a postbiotic is that even when it is dead, it still has beneficial health effects when ingested. These beneficial effects have been seen in studies of both stressed animals and stressed humans. 

Theoretically, the beneficial effects of a postbiotic like HT-PS23 could come from interactions between human and/or microbial cells in the gut and chemical components of HT-PS23 such as its cell wall, metabolites, or other components.

If you want to get really technical about it, HT-PS23 is unique in that it is a dead probiotic as well as a postbiotic: 

• It is a postbiotic because it is dead and has beneficial health effects when in this dead state.
• It is a dead probiotic because, while alive, it also has probiotic properties. 

Postbiotics do not need to be dead probiotics. They can be dead bacteria that have beneficial effects. Yet, HT-PS23 is both a dead probiotic and a postbiotic. 

Can you tell me more about the beneficial health effects of HT-PS23?

Dr. Patno:

Sure! The clinical evidence shows an impact of HT-PS23 on both perceived stress as well as stress that is induced in a physically-demanding situation. 

A randomized, placebo-controlled trial evaluated the impact of HT-PS23 on stressed nurses. This kind of study is the gold standard of clinical trials: randomized, placebo-controlled, and published in a peer-reviewed journal. Because HT-PS23 was shown to reduce stress in this study, we knew that it should be in Bened Life’s Neuralli Mood.

In the study, the nurses took 20 billion heat-treated cells of PS23 per day for eight weeks or the placebo. And here’s what happened:

Overall, those who took HT-PS23 had reduced blood cortisol levels compared to those who took placebo. This reduction in the stress hormone suggests a systemic stress response effect. 

In addition, the nurses completed questionnaires that evaluated how stressed or how anxious they felt. For those nurses who started out with higher stress scores, they reported an increase in job satisfaction after taking HT-PS23 for eight weeks. The nurses who reported feeling more anxious at the beginning perceived a reduction in their anxious feelings after taking HT-PS23 over the course of the study. 

Thus, HT-PS23 reduced anxious and stressed feelings while simultaneously reducing the stress hormone that systemically activates the body’s stress response.

So HT-PS23 has beneficial mental health effects?

Dr. Patno:

Yes! While most people think of probiotics and postbiotics as primarily affecting gut health, there are certain probiotic and postbiotic strains that are able to help mental health. These strains may or may not have gut health benefits as well. 

How do you think HT-PS23 works to reduce stress?

Dr. Patno:

Our best clues for how HT-PS23 works are from studies of animals, their microbiomes, their neurotransmitters, and their stress-induced behaviors. 

In a preclinical study evaluating behavior under stress, HT-PS23 led to increases in Bifidobacteria, a genus of bacteria that is considered part of the healthy gut microbiome. Stressed animals had lower levels of dopamine in the prefrontal cortex and hippocampus, while HT-PS23 helped bring those dopamine levels back up. At the same time, the stressed behaviors in the preclinical model were reduced by giving HT-PS23. 

Another model of early life stress showed reduced mobility and exploratory behavior, both of which HT-PS23 improved. In addition, HT-PS23 influenced dopamine metabolites in the hippocampus, an area involved in memory and learning. At the same time, the stress hormone was reduced, and a protective immune cytokine was increased. Thus HT-PS23 may impact learning and memory processes through its ability to affect dopamine metabolism in the brain under stressful conditions.

Preclinical studies also hint at benefits of HT-PS23 in intestinal barrier integrity and a healthy intestinal immune response, as well as possible influences on motor function, memory, and reduced anxiety-like behaviors in aging.

So HT-PS23 influences dopamine levels in the brain. That sounds similar to PS128, the other strain in Neuralli Mood. Does PS128 also help with stress in people?

Dr. Patno:

Yes, we have two clinical studies that suggest it can. A group of stressed IT specialists completed questionnaires and provided saliva before and after taking PS128, and their results showed improvements in sleep, gut health, and mood with a reduction in salivary cortisol. A double blind randomized controlled study (RCT) of insomniacs taking PS128 showed improvement in sleep quality and mood. 

Interestingly, PS128 has also supported immune biomarkers, post-exercise recovery, and strength, as well as performance in small RCTs in triathletes and half-marathoners.

What other benefits could people maybe experience from taking HT-PS23 in Neuralli Mood?

Dr. Patno:

Based on a study with athletes, HT-PS23 could possibly help with physiological stress. Two days after an intense exercise bout (100 maximal vertical jumps), clinical study participants recovered faster with HT-PS23 rather than placebo in this double-blinded, randomized trial. Their strength was not as affected after such an intense workout, and biomarkers of delayed onset muscle soreness (DOMS) were lower.

If HT-PS23 is beneficial in its live form, why use it as a postbiotic?

Dr. Patno:

In the postbiotic form, it has the advantage of a longer shelf life. And while PS23 has passed safety studies in its live form, the dead form has the advantage of not being able to reproduce and thus not developing bacterial growth in an unwanted location (if somehow an accident occurred that transferred live bacteria to an unintended place such as the bloodstream).

In other words, a postbiotic cannot “colonize” the gut.

You mentioned that HT-PS23 is found in the human gut. Does this mean that it is safe?

Dr. Patno:

Just because a strain is isolated from healthy humans, it doesn’t mean it is “safe” in terms of passing safety standards for probiotics. PS23 had to pass the same safety tests as every other Bened Life strain, including those isolated not from humans but from plants, like PS128.

First, PS23 was evaluated for known genes that could potentially have a side effect. For example, bacteria can transfer their genes to other bacteria which might turn them into “superbugs” that are difficult to remove with antibiotics. This so-called “horizontal gene transfer” can occur from microbe to microbe co-existing in communities, like in the gut microbiome, as opposed to the vertical transmission of genes from parent to the next generation. 

The result of these tests revealed that PS23’s genome did not contain the undesirable genes that were in the database of known factors. In addition, the PS23 genome did not contain genes that would produce biogenic amines such as histamines, but it did have one that was similar to such a gene. Thus, it was tested in vitro, and that enzyme activity was not present. Thus, PS23 passed multiple safety tests. 

Other safety tests that PS23 passed were conducted in preclinical models. Various amounts of PS23 from low to high were provided and negative effects were not observed. Instead, both live and heat-treated PS23 showed benefits in a preclinical model of intestinal immune response. 

In short, HT-PS23 is considered safe because it has passed certain safety tests, the same standard applied to all Bened Life strains. And we hope it helps a lot of people!

(Click to visit the Neuralli Mood product page.)

Recommended reading:

What to Know about Neuralli Mood

What Are Postbiotics?

What Is the Gut-Brain Axis? How Your Microbiome Can Influence Wellbeing