Probiotics Don’t Change Fecal Microbiota Populations. This Is What One Review of Seven Studies Says. And I Care, Why?

 gut bugs









Back on the Subject of Bugs…Again!

Why am I on the subject of bugs again? Well, let me take you back in time to answer this question.

Earlier today, in an office far, far away, I was priming my brain for my next task of writing. I was lost in thought and innocently reading a great blog on fermented foods by Dr. Mercola. As I nonchalantly clicked on a cross reference, little did I realize I would soon be, well, bugged by it for the rest of the day.  Now mind you, it was a good blog. It was on the value of eating fermented food and nurturing ourselves with a whole food diet. This was okay, even loved, be me. I was even fine with the fact that there wasn’t a mention to be cautious with consumption of fermented products in histamine sensitive people. I mean, a blog can only go for so long, right. 😉

What bothered me was that it stated that probiotics may not be as valid an intervention as eating these whole food sources of critters. This was due to the fact that one review of seven studies found they didn’t significantly change fecal stool samples. Dolt! (Picture me slapping my forehead here.) Being someone who will change and admit she is wrong when science and clinical evidence reexamines a “truth”, one review does not a conclusion make.

So, as I took a little deep breathing break and made friends with the stress by grabbing a bottle of rosemary and peppermint essential oil, I was able to clear my pre-oil thought pattern. To give you an idea, this is what my poor brain went through: “No! Nah. (Huff noise). Oh. What! Oh geez! Who cares! Oh, this must be the blog for the day then! …” You get the picture.

So, when I was calmed down, I did a mini investigation of all that I knew. I even took a major detour pathway down microbial DNA analysis line. Warning, don’t go there!!

I came back to my conclusion that there’s actually a lot of evidence that probiotics modulate many health factors, even if some reviews didn’t find a big change in poo. Some studies did. I even wrote about one trial a few months ago. Still, I don’t care if there’s not always a change in poo in studies. This is because probiotics can do more than change our microbe count in our solid excretions. (Sorry, there’s only so many times I can write “poo.”)

For example, in a double-blind, placebo-controlled randomized trial with 62 children with a peanut allergy, researchers examined the effect of the probiotic Lactobacillus rhamnosus (CGMCC 1.3724) and peanut OIT (probiotic and peanut oral immunotherapy [PPOIT]). The authors sought to determine if the children would stay unresponsive to the allergen 2 to 5 weeks after discontinuation of treatment (referred to as possible sustained unresponsiveness). Desensitization, peanut skin prick test, and specific IgE and specific IgG4 measurements were secondary outcomes. Though the study was short, it showed that probiotics had an effect on immune modulation, and no poo was collected! Here’s the impressive results:

Possible sustained unresponsiveness was achieved in 82.1% receiving PPOIT and 3.6% receiving placebo (P < .001). Nine children need to be treated for 7 to achieve sustained unresponsiveness (number needed to treat, 1.27; 95% CI, 1.06-1.59). Of the subjects, 89.7% receiving PPOIT and 7.1% receiving placebo were desensitized (P < .001). PPOIT was associated with reduced peanut skin prick test responses and peanut-specific IgE levels and increased peanut-specific IgG4 levels (all P < .001). PPOIT-treated participants reported a greater number of adverse events, mostly with maintenance home dosing.


Microbiome Review for the Smarties

iStock_000041177846Large (2)For those who need a refresher from the beginning, our microbiota is the ecological community of microorganisms living in, on, and around our body. “Microbiome,” which is technically the genomics of the little buggers, is often used interchangeably in the literature as the subject of these bug inhabitants grew in popularity. The vast amount of research on the microbiome that continues to be released on a daily basis is astounding. In fact, the sheer volume of articles and blogs that load my inbox can make this somewhat obsessive and nerdy critter lover go a bit cross-eyed at times.

The more that is learned, the more avid bug followers are awed by their wonders and complexities. We also are humbled by how much we still don’t know. In fact, just recently the previously held notion that bugs outnumbered human cells 10-to-1, was put to question.

Still, regardless of how many critters line our insides, it isn’t necessarily their quantity that determines their impact on our body processes.  Rather it’s through the various actions they perform and the interactions with our own cells that modulate our health that is probably the most important. (Click here to read about two cool studies on the association between microbiome populations and multiple sclerosis).


But What About Swallowing Bugs?

So our microbiome fingerprint is linked to disease processes, but can swallowing bugs, AKA probiotics, really make a difference? Although, even just a few years ago, the limitations of culture techniques, translation from animal to human trials, methodology of studies (doses, duration, subjective measurements, biases, and strains used) were creating question on the efficacy of probiotics as clinical interventions, today, this is changing. There is now more evidence on how microbes modulate our mental and physical health.

Besides the vast amount of research on the connection between our gut bugs and physical diseases, the research has gone buggy in another way. The term “pscyhobiotics” was defined in a 2013 study in Biological Psychiatry as, “a live organism that, when ingested in adequate amounts, produces a health benefit in patients suffering from psychiatric illness. As a class of probiotic, these bacteria are capable of producing and delivering neuroactive substances such as gamma-aminobutyric acid and serotonin, which act on the brain-gut axis.”  

In fact, I just found a 2014 study on how certain microbe populations may even encode for specific neurotransmitters, in a small amount of the population. This was not a human or rodent trial, but I did find another review from 2016 which explored this gut-brain connection and the microbial impact on the nervous system, including their effect on the tryptophan pathway. The authors reported that these influences can lead to modulation of mood and immune function.

As far as physical health, a 2003 review determined the efficacy of probiotics on gastrointestinal issues and diarrhea, as well as early trials of their promise in infectious diseases, cancer, allergies, urogenital and reproductive issues in females. Also, it’s hard to dismiss all the clinical trials with the happy fungus, Saccharomyces Boulardii. Dr. Christianson did an awesome review with many clinically relevant references, including its use for immune modulation, intestinal integrity, skin health, calming inflammation, and digestive health. This is why this probiotic is my favorite for most by the way and why it’s on my store.

In a later analysis the clinical findings in the use of probiotics for gastrointestinal health and the importance of probiotic considerations on efficacy was also outlined. Their questions presented may explain mixed results found in some studies:

Many questions related to efficacy, viability, most optimal dose, and method of delivery remain:

  1. The optimal number of colony forming units (CFUs) for each bacterial strain delivered remains unknown. Doses in human trials are based on those used in animal studies despite the differences in intestinal surface area. Dose–response studies are generally lacking. Commercially available probiotic formulations typically have at least 106?CFUs, but they may range up to 1012?CFUs.
  2. Very few studies have actually documented survival of an administered probiotic as it transits the gut, by means of fecal recovery studies. One probiotic may not necessarily be translatable to other probiotic(s): for example, different Bifidobacterium species have different tolerances to acid and growth requirements and will have different fecal recovery rates [Matto et al. 2004; Takahashi et al. 2004].
  3. The method of delivery, i.e. yogurt versus milk, may have an impact on the viability and number of bacterial colonies. Furthermore, only one strain of B. longum could survive in fermented milk for 2 weeks [Takahashi et al. 2004].
  4. Probiotics may produce their effects with viable as well as nonviable bacteria, suggesting that metabolic or secreted factors or structural or cellular components may mediate their immunomodulatory activities [Borchers et al. 2009]. Furthermore, several experiments indicate that the ability to induce secretion of various cytokines is mediated by and large by cell wall components [Borchers et al. 2009].
  5. Different probiotic species and genuses may have different immunological and physiological effects in different disease states. Wagner and colleagues showed that different Lactobacillus species have different efficacy in preventing fungal sepsis in mice [Wagner et al. 1997].
  6. The composition of colonic bacterial microflora appears to change with aging (age >60 years). It is unknown whether elderly patients should be treated with different probiotics than young patients [Enck et al. 2009].
  7. Combination probiotics may interact and have an impact on host intestinal flora differently than single probiotic preparations.
  8. Optimal duration of probiotic treatment and durability of response are unknown. How long a given probiotic will take to colonize, alter the microflora, and have an impact on immune function remains uncertain. There is significant heterogeneity in treatment duration in the human studies, likely contributing to the differences in reported results.

So, taking all these factors into mind…


Back to What Bugged Me

superbugs and oilsLet’s go back to the excerpt that gave me the creepy crawlies in Epoch Times. It stated:

The review of previous research on the topic, conducted by researchers at the University of Copenhagen, found no evidence that probiotics improve the balance of gut bacteria in healthy adults. While further clinical research is required to dig deeper into these findings, the results certainly contribute to the broader lingering concern that products marketed as healthy may not be so good for your health (or your pocket) after all.

The feeling that many of us may have been duped into buying “all singing, all dancing” probiotic brands comes at a time when people are increasingly migrating away from the supermarket to instead embrace homemade produce – including the use of home brewed fermented foods for hopes of a healthier gut.

However, as mentioned above, there have been studies that show differences. I mentioned the previous blog I wrote about this. Another one of my favorites demonstrates that even low doses of probiotics can cause changes in the microbiota population in the gut which indicated their role in immune modulation and changing the milieu rather than “repopulation.” Furthermore, a review in Therapeutic Advances in Gastroenterology discusses some evidence of how probiotics modulate health in a variety of ways and change the microbiota present. Here’s a long excerpt that goes into the nitty-gritty details if you are interested:

The effects of probiotics on the composition, diversity and function of the gut microbiota have been studied using different tools and techniques ranging from targeted, culture-dependent methods to metagenomic sequencing. However, not many studies have demonstrated associations of altered microbiota following treatment with probiotics. A clinical study demonstrated decreased pain and flatulence in patients with IBS that received a 4-week treatment with a rose-hip drink containing 5 × 107 colony-forming units (CFU)/ml of L. plantarum DSM 9843 per day [Nobaek et al. 2000]. This improvement in clinical symptoms was associated with the presence of L. plantarum in rectal biopsies of patients, along with reduced amounts of enterococci in fecal specimens. A more recent study focusing on patients with diarrhea-dominant IBS (IBS-D) yielded symptomatic relief in patients treated with a probiotic mixture of L. acidophilus, L. plantarum, L. rhamnosus, Bifidobacterium breve, B. lactis, B. longum and Streptococcus thermophilus. Interestingly, analyses of the fecal microbiota of these patients using denaturing gradient gel electrophoresis (DGGE) revealed that the similarity of the microbial composition was more similar in probiotics-treated patients than that of the placebo group. This observation suggested that microbial community composition was more stable during the period of probiotics treatment [Ki Cha et al. 2011].

Recent technological innovations in DNA sequencing and advancements in bioinformatics have provided scientists with tools to explore research questions related to the human microbiome and how treatment modalities affect changes in global composition and function of the microbial communities. A recent study [Cox et al. 2010] using a high-throughput, culture-independent method analyzed the fecal microbiota of 6-month-old infants treated with daily supplements of L. rhamnosus (LGG). Results showed an abundance of LGG and an increased index of evenness in the fecal microbiota of these infants, suggesting ecological stability. The ability of probiotics to induce changes in intestinal microbial communities was demonstrated by a recent study, which explored the effects of L. reuteri on microbial community composition in a neonatal mouse model using 16S rRNA metagenomic sequencing. Results from this study demonstrated a transient increase in community evenness and diversity of the distal intestinal microbiome in animals treated with L. reuteri compared with that of vehicle-treated animals [Preidis et al. 2012]. The diversity in microbial communities was shown to be associated with increased ecological stability [Eisenhauer et al. 2012]. The loss of species in a community, although not immediately visible, can result in diminished ecological resilience after a stress-related perturbation [Peterson et al. 1998]. Interestingly, reduced microbial diversity was associated with diseases such as Crohn’s disease [Manichanh et al. 2006] and eczema in early life [Forno et al. 2008]. Probiotics may induce changes in the intestinal microbiota and stabilize microbial communities. However, further studies in humans are needed to assess whether probiotics can make the same impact on the human intestinal microbiome and whether the changes are associated with clinical benefits in the host.

In addition to directly affecting the composition of the intestinal microbiota, probiotics may also modulate the global metabolic function of intestinal microbiomes. Fermented milk products containing several probiotics did not alter the composition of intestinal bacterial communities in gnotobiotic mice and monozygotic twins [McNulty et al. 2011]. However, fecal metatranscriptomic analysis of probiotics-treated animals demonstrated significant changes in expression of microbial enzymes, especially enzymes involved in carbohydrate metabolism. Moreover, mass spectrometric analysis of urinary metabolites revealed altered abundance of several carbohydrate metabolites. These observations suggested that probiotics may affect the global metabolic function of the intestinal microbiom


Why One Study Does Not Make a Conclusion

Let’s look at the methods of this study that dissed probiotics, keeping in mind the caveats expressed above:

In the present review, the primary outcome of interest is alterations in fecal microbiota composition, which was assessed by either microarray hybridization (HITchip (n?=?1) [22], HTF-Microbi.Array (n?=?1) [23]), or next-generation sequencing methods (16S rRNA sequencing on Ion Torrent PGM (n?=?1) [27], Illumina MiSeq platforms (n?=?1) [24], or 454 pyrosequencing (n?=?2) [19, 21]), or metagenomics on a SOLiD 5500×l platform (n?=?1) [20]. Of the studies using a 16S rRNA-based approach, one did not report which hypervariable region of the 16S rRNA gene was targeted and no studies targeted the same set of regions. The databases used for mapping the sequences were GreenGenes version 13.5 (n?=?1) [27], RDP (MultiClassifier 1.1 or not specified) (n?=?2) [19, 24], or both (versions not specified) (n?=?1) [21], while two did not report the database used. The study by Brahe et al. [20] used metagenomics and mapped reads to a reference catalogue of 3.3 million bacterial genes [34].

Do you see what I bolded and why results may have come out a little skewed? This one little paragraph led me down a very scary road trying to cross reference different methodologies of DNA analysis of critters and bacteria. In the interest of your time and my sanity, that will need to be saved for another time, if ever, but the basics can be found on Wikepedia. Though not my favorite source for unbiased data, it can give you an idea of complexity.



So, I’ve reached the end of my rant. This little event proved to me once again how important it is to consider the big picture of the overall conclusions from various trials, reviews, and meta-analyses. When reviewing microbiota data, I try to determine the methodology of the study, as well as individualized microbiome fingerprint of the subjects, and the certain strains studied, among other factors.

If one wants to determine the efficacy of probiotics by a change in poo, that may be a little short sighted in research studies. Though the therapeutic and clinical correlations with finding pathogens in functional stool tests has been helpful in individuals with microbial overgrowth, feces do not tell the whole story of our gut population and the action of probiotics in our bellies.

The discovery of the trillion tiny friends and the new methods we have to study them has connected the dots of why we are what our microbes eat and how the critters that line our insides effect our health. This is why taking good care of our little friends with healthy diet and lifestyle is important. In other words, if we treat ‘em bad, there’s a backlash on us.


What I Suggest

I have studied microbes for a while now, and I do my best to stick with the products that have clinical validation and I’ve seen efficacy with. I also follow my clients and their responses. Due to their immunomodulatory effects, it is possible that even the “good guys” can cause imbalances in an individual with a different microbiome fingerprint.  I also make sure their mind-body and gut stays healthy and I keep their optimal population of critters with the use of the secondary metabolites found in essential oils.

If you to dig in more on the studies on probiotics, I encourage you to read this review here. I really liked how fermented foods and probiotics were included.

Oh and to order quality probiotics, check with your integrative practitioner who gets the clinically researched ones… or go here.



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