Gut Microbiome in HIV

A recent article, technical as usual, looked at the kinds of bacteria found in the intestines of people living with HIV vs those uninfected (and included one long-term non-progressor who has lived 21 years without treatment and no progression). What they found was described beautifully in this post with embedded video.

The idea presented was that perhaps we can help reduce bodywide inflammation by establishing a more healthy bacterial profile in the gut. An idea we have been talking about for decades!! And indeed, this is why we have proposed the use of agents like glutamine (which help the cells lining the gut called villi to turnover), along with probiotics and prebiotics (fiber and/or beta glucans). These are rather blunt tools but do seem to help improve gut function. We do have some data on the use of probiotics in the management of HIV-related diarrhea and for bacterial vaginosis (and our sister organization, FIAR, is working on a meta-analysis on those data). While these kinds of interventions have some benefit, ultimately, understanding what one’s ideal “microbiome fingerprint” is — what is the balance of different types of bacteria that colonize your gut under uninfected conditions — and figuring out how to replace that may provide a substantial improvement in clinical condition, dramatically reducing bodywide inflammation that may persist even under conditions of antiviral suppression.

See the NYBC website for more information on PROBIOTICS

 

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Probiotics Conference Report

Below is a report on a recent conference on one of our favorite categories of supplement–PROBIOTICS.
We aren’t surprised that prestigious scientific organizations like the New York Academy of Sciences devote their resources to spreading the word about Probiotics. Over the last 100 years, these “friendly bacteria” have been the subject of an enormous amount of scientific study, confirming their crucial role in maintaining the human body’s immune system. And we also know that many NYBC members over the years have benefited from use of Probiotics such as the Jarrodophilus line from Jarrow, or Florastor (Saccharomyces boulardii). For a full list of these Probiotics, with indications for their use and dosing recommendations, see the NYBC catalog at PROBIOTICS AT NYBC

Report on
Probiotics, Prebiotics, and the Host Microbiome:
The Science of Translation
Wednesday, June 12, 2013 | 7:45 AM – 6:00 PM
/The New York Academy of Sciences
George M. Carter

This was a day-long series of discussions, with nearly 70 posters that brought together a variety of researchers, clinicians and, of course, pharma reps sniffing around for profits.  And all about the horrors of–BACTERIA! Of course, some bacteria cause disease…but most of them not only don’t, but we need them to live. And there are indeed a lot of them!

These good ones, when they are found in the diet or as a supplement, are known as probiotics, such as acidophilus or bifidobacteria. They are found, for example, in yogurt or other fermented foods. Prebiotics, on the other hand, are substances that help to facilitate the growth of those good bacteria, but are otherwise non-digestible. They include fiber (soluble or insoluble) and agents such as beta glucans, inulin and oligosaccharides.

There seemed to be a general feeling of anticipation as our knowledge grows about the microbes we share—and depend upon for our survival. Various populations of microbes live in distinct communities on and in our bodies. Each bacterium has its own set of DNA, just like each of our human cells (except cells like platelets and red blood cells). All of our human cell  DNA contributes about 25,000 genes. By contrast, if you add up all the “bugs” in and on our bodies, that figure runs into the MILLIONS of genes, recent estimates placing the number at about 8 million. And if you removed all the microbes from your body, aside from killing you, that entire amount of bacteria would weigh up to 3 pounds!

That collection of microbes and their genes and gene-products are known as the microbiome.  This is a complex system of various species of bacteria that interact with the host (us) and other bacteria. They tend to form ecologies at various sites so that the crew found in your nostrils may not be the same as that found in the gut, the vagina, or on the skin, for example. And the patterns of bugs that colonize us are different from person to person to some degree—and even change over the course of a lifetime.

These various types of bacteria are categorized by their taxonomy. Taxa refers to the genus, species and strain of the bacteria; for example, you may have heard of Lactobacillus acidophilus, often found in enriched yogurts. “Lactobacillus” is the genus name and “acidophilus” is the species. These also may be divided into further subtypes known as strains, so one strain is L. acidophilus L1, used to feed cattle to reduce the amount of bad bacteria such as E. coli O157:H7.

And these bacteria are necessary for our survival. They perform a huge number of functions, including producing some vitamins, training our immune systems, blocking bad bacteria from growing, and even altering our moods. They communicate within and between species of bacteria, as well as with our body. Some of them may cause trouble, including Helicobacter pylori (ulcers) and Clostridia difficile (colitis). How best to treat a dysbiosis (=microbial imbalance on or inside the body)  is evolving as we increase our understanding of the relationships and ecologies of these bacterial communities.

The alterations in the nature of these communities arise from the time we are born. If one is born by a Caesarean, one tends to get more of the microbes of the mother’s skin as opposed to the vaginal microbial system that the infant collects during a vaginal birth. Whether this has any longer term clinical impact remains unclear, though some evidence suggests that those born by Caesarean may be at higher risk of allergies or asthma. The microbiota tend to establish themselves as a more adult phenotype by the tender age of 2 or 3.  Some researchers are developing models that look at similarities in the patterns of the microbes such that people are divided into 2 or 3 enterotypes.Although this attempt at classification is still evolving, it may help us see how an individual’s response to or problems with host bacteria can be understood and managed.

Indeed, some of the sessions focused on new discoveries of particular bacteria that appear to be associated with protection from certain diseases, or may be implicated in causing disease. One group discussed their findings of a putative association of Akkermansia muciniphilia with the development of diabetes, while others focused on patterns of the microbiome that might underscore a potential for obesity. Many of the sessions were devoted to research in mice, which was moderately interesting from an academic perspective. Others looked at the inter-relationship between probiotics and brain function as well as “gut feelings” (the gut containing what some have dubbed a second brain’s worth of neuronal innervation).

This raised some  issues abouthow to study these agents in the context of a Food and Drug Administration that is at the least bureaucratically hostile to the study of dietary supplements and currently forbids them to be marketed as preventing, curing or mitigating diseases. Discussion was devoted to these challenges, but I think it failed to get to the heart of the matter, namely, that we need—VERY carefully[1]—to address how to create rulemaking with regard to Investigational New Drug requirements that does not require an absurd level of documentation of safety for products ALREADY on the market and in widespread use!

Other studies in humans can avoid the onerous process of acquiring an IND by using a primary endpoint (what the study seeks to establish) that is more in line with either the supplement’s use as a “medical food” (a very narrow definition), or that seeks to improve outcomes to structure or function of the body (the currently allowed dietary supplement claim).

The frightening prospect, to me, was the pharma reps sniffing around, no doubt seeing how they can “capitalize” on and/or patent products to extract huge profits. The notion of “public-private” partnerships in this arena gives me the horrors as it usually means taking away access except for the wealthy. We’re talking about products found in yogurt that have been used for millennia!

Still, the day also had a couple of remarkable and straightforward studies. The most exciting was the work of a group who helped women in various nations in Africa to produce their own probiotics and yogurt. This had the added advantage of creating an economic opportunity for the women, increasing respect from male householders as they brought in income while also improving health outcomes. This was augmented even more by the addition of a powder of the dried leaves of Moringa, a plant that grows like a weed from South America, throughout Africa, South and Southeast Asia, and which has a good array of micronutrient vitamins and minerals. Not in huge amounts, but fairly comprehensive.

A speaker from Scotland, Mr. Burns, also discussed the kind of “grassroots” organizing that they undertook in Scottish hospitals to translate research into the public health sphere. The point of this exhilarating talk was how to get from the bench to the bedside—in short, he was promoting a very comprehensive strategy for creating awareness among physicians and others, working with district leaders and hospital administrators. Their efforts got them, for example, to adhere more closely to checklists for surgeries and pneumonia management. By requiring and getting more attention to these matters, they were able to successfully, and dramatically, drop death rates. Some of these programs have run now for over 10 years, and involve getting physicians and others to prescribe probiotics or prebiotics and  actually use them in preventing C. diff. or better management of bacterial vaginosis,or management of HIV-related diarrhea!

It was a day packed with information and interesting people. I attended with Dr. Henry Sacks of Mount Sinai School of Medicine, with whom I have been working on a grant from the National Institutes of Health to undertake meta-analyses of various questions relating to the use of Complementary and Alternative Medicine (CAM) approaches to managing HIV disease and ARV side effects. We are finishing up work on our first two questions, the use of a multivitamin/mineral among HIV+ people, and the management of peripheral neuropathy with Cannabis sativa. Our next question, which we are now beginning to work on, is the use of probiotics!

For more information, abstracts and so forth, please visit the NYAS website.

______

Footnote:
[1]  Any changes in IND rulemaking should be careful to avoid opening the floodgates to drug companies using such changes to weaken safety or oversight of new drugs, of course. Accelerated approval has been abused by the companies to push more drugs more rapidly onto the market that are NOT medically superior or addressing a desperate need as antiretroviral drugs were in the mid-90s.

Probiotics found effective for antibiotic-related diarrhea

A recent review article that pooled findings from more than 11,000 patients concluded that probiotics were effective for preventing and treating antibiotic-associated diarrhea. About 30% of people treated with a course of antibiotics develop diarrhea, so this is a significant medical issue. Types of probiotics reviewed include Lactobacillus and Saccharomyces boulardii; both were found effective. See NYBC’s entries under Probiotics for details on how to use.

Reference: Hempel S, et al “Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis” Journal of the American Medical Association 2012; 307: 1959-1969

Gut microbes important for health

As this story notes, the bacteria in our guts are important for a variety of health issues, including production of vitamins as well as protecting the immune system. They note a study indicating that the use of probiotics (like acidophilus, bifidus and the like) can help reduce the insulin resistance seen with type II diabetes.

The article is a short review of a presentation given by Professor Willem M. de Vos at the fourth Environmental Microbiology Lecture: “Microbes Inside” on October 10, 2011.

NYBC has a variety of probiotics in different forms.

Supplements for Diarrhea and Malabsorption

We’re reprinting below the NYBC recommendations
for supplements that address the common gastrointestinal
problems of people with HIV:

Diarrhea. This is one of
the most common side effects of
antiretroviral drugs–especially protease
inhibitors. When it occurs, make
sure to drink plenty of (healthy) fluids
to replace electrolytes (potassium,
sodium, and magnesium ions) and
prevent dehydration. Avoid sugary
and/or caffeinated beverages.
One of the simplest remedies: bananas!
Adding a yogurt with active
cultures to your regular diet can also
improve diarrhea. In addition to adding
beneficial flora to your gastrointestinal
tract, yogurt is nutritionally
rich in protein, calcium, riboflavin,
vitamin B6 and vitamin B12.

However, for some, dietary changes may
not be enough to control the diarrhea
Supplements to consider in treating
diarrhea associated with protease
inhibitors include calcium, and glutamine
(up to 20-40 grams daily for
diarrhea while it persists). There are
some clinical data to support these
interventions. A note of caution: calcium
carbonate works fine but should
be avoided if you are using atazanavir
[Reyataz].

If diarrhea is associated with the use
of antibiotics, go probiotic! Use acidophilus,
bifidus or Saccharomyces
boulardii
(Florastor) to control C.
difficile (a problem frequently encountered
with antibiotic use) and to improve gut function.
Use of digestive enzymes may also help to improve
digestion (e.g., lipase, protease, amylase, and
lactase).

Malabsorption is the difficulty in digesting or
absorbing nutrients from food. It’s a widespread
problem among HIVers, and a serious
one at that. HIV disease damages the
guts, where it is estimated that 80%
of the disease “lives,” hindering the
digestive tract’s ability to absorb nutrients
(or meds). Additionally, many
HIVers actually have too little acid
in their stomachs – a little-discussed
condition. This can cause the sphincter
at the opening of the stomach to
fail to close properly, resulting in
GERD: gastro-esophageal reflux disorder.
In general, gut function can be
improved with probiotics such as
acidophilus and bifidus, as well as
2-5 grams of glutamine, taken daily.
Further, digestive enzymes that help
break down fats, carbs and proteins
may be useful in promoting better
absorption. Again, a good diet and
a potent multi are important starting
points!

See the NYBC entries for more detailed
recommendations regarding these supplements:

Glutamine Powder:
http://nybcsecure.org/product_info.php?cPath=49&products_id=128
or Glutamine Caps:
http://nybcsecure.org/product_info.php?cPath=49&products_id=127

Douglas Vegetarian Enzymes:
http://nybcsecure.org/product_info.php?cPath=49&products_id=264
Jarro-Zymes Vegetarian Enzymes:
http://nybcsecure.org/product_info.php?cPath=49&products_id=335

Ultra Jarro-Dophilus (probiotic):
http://nybcsecure.org/product_info.php?cPath=27&products_id=354
Jarrodophilus EPS (No refrigeration needed):
http://nybcsecure.org/product_info.php?cPath=27&products_id=199
Saccharomyces boulardii (Florastor):
http://nybcsecure.org/product_info.php?products_id=217

Acidophilus and Gut Flora

A BBC story today reports that scientists are considering the vast variety of flora that colonize our guts as a “second genome” that has yet to be fully explored. They managed to create a metagenome that contains the sequences of all the bacteria that hang out with us.

These bacteria are important in so many ways. As the article notes: “The bacteria help digest food, provide vitamins, protect us from invading pathogens. If there’s a disturbance, people get all sorts of diseases such as Crohn’s disease, Ulcerative colitis, and a link has also been made to obesity.”

And indeed, in HIV disease, the gut is severely damaged from the get-go. HIV infection hangs out there–where many of the CD4+ T cells hang out. So would supplements of things like acidophilus or bifidus make sense? Indeed, there HAVE been clinical studies that show a positive benefit, for kids with HIV to adults (see the abstract below).

Add to that, many people take antibiotics either to treat a concurrent infection or as prophylaxis, and you add the further damage to the gut caused by the death of these friendly gut flora. Replacing this even during treatment (i.e., taking the acidophilus as many hours from the antibiotic) can help.

Further, studies are ongoing for use of vaginal application of acidophilus among women both as a spermicidal and to prevent vaginal candidiasis (see, e.g., J Assoc Nurses AIDS Care. 2001 Jul-Aug;12(4):51-57). It can also help babies.

This seems to be one of those cornerstone therapies that are relatively inexpensive.

***
Trois L, Cardoso EM, Miura E. Use of probiotics in HIV-infected children: a randomized double-blind controlled study. J Trop Pediatr. 2008 Feb;54(1):19-24. Epub 2007 Sep 17.
Department of Nutrition, Unilasalle, Brazil. liviatrois@gmail.com

HIV/AIDS is an infection characterized by immune cell dysfunction and subsequent immunodeficiency, as well as intestinal disorder. Probiotics are live microbial feed supplements that beneficially affect the host animal by improving intestinal microbial balance and promoting health benefits. The goals of this study were to determine whether the use of probiotics could improve the immune response determined by CD4 cells mm(-3) counts and reduce liquid stool episodes. A randomized double-blind controlled trial with 77 HIV-infected children (2-12 years), divided into two groups: one receiving probiotics (formula containing Bifidobacterium bifidum with Streptococcus thermophilus -2.5 x 10(10) colony forming units) and the other, a standard formula (control group), for 2 months. The CD4 counts (cells mm(-3)) were collected at the beginning and end of the study. The quality and number of stools were assessed by a questionnaire (watery to normal stool consistency). There was an increase in the mean CD4 count in the probiotics group (791 cells mm(-3)) and a small decrease in the control group (538 cells mm(-3)). The change from baseline in mean CD4 cell count was +118 cells mm(-3) vs. -42 cells mm(-3) for children receiving the probiotic formula and control formula, respectively (p = 0.049). A similar reduction in liquid stool consistency in both the groups (p < 0.06), with a slight enhancement in the probiotics group, was observed, but without significant difference (p < 0.522). The incidence of loose-soft stools showed a small decrease in both groups (p < 0.955) and there was an increase in the incidence of normal stool consistency in both the groups (p < 0.01). Our study showed that probiotics have immunostimulatory properties and might be helpful in the treatment of HIV-infected children.

**
Asia Pac J Clin Nutr. 2007;16 Suppl 1:318-22.
Advances in nutrition support for quality of life in HIV+/AIDS.

Suttajit M.

School of Science and Technology, Naresuan University, Phayao Campus, Phayao, Thailand 56000. msuttjit@mail.med.cmu.ac.th

Globally, acquired immunodeficiency syndrome (AIDS) is an epidemic, severe and fatal disease. Along with the etiological factors of human immunodeficiency virus infection (HIV+) and decreased immunity, there are a number of other risk factors including opportunistic infection, malnutrition, wasting syndrome, and oxidative stress. The nutritional problems have been shown to be significant and contribute to health and death in HIV+/AIDS patients. Weight loss, lean tissue depletion, lipoatrophy, loss of appetite, diarrhea, and the hypermetabolic state each increase risk of death. The role of nutrition and how oxidative stress is involved in the pathogenesis of HIV+ leading to AIDS is reviewed. Studies consistently show that serum antioxidant vitamins and minerals decrease while oxidative stress increases during AIDS progression. The optimization of nutritional status, intervention with foods and supplements, including nutrients and other bio-active food components, are needed to maintain the immune system. Various food components may be recommended to reduce the incidence and severity of infectious illnesses by forms of bio-protection which include reduced oxidative stress due to reactive oxygen species which stimulate HIV replication and AIDS progression. Probiotics or lactic acid bacteria and prebiotics are sometimes given on the presumed basis that they help maintain integrity of mucosal surfaces, improve antibody responses and increase white blood cell production. People with HIV+/AIDS can be informed about the basic concepts of optimal nutrition by identifying key foods and nutrients, along with lifestyle changes, that contribute to a strengthened immune system. Moreover, nutritional management, counseling and education should be beneficial to the quality and extension of life in AIDS.

***
If you can, eat yogurt daily!
J Clin Gastroenterol. 2008 Mar;42(3):239-43.
Yogurt containing probiotic Lactobacillus rhamnosus GR-1 and L. reuteri RC-14 helps resolve moderate diarrhea and increases CD4 count in HIV/AIDS patients.

Anukam KC, Osazuwa EO, Osadolor HB, Bruce AW, Reid G.

Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Benin, Benin City, Edo State, Nigeria.

HIV/AIDS is changing the human landscape in sub-Saharan Africa. Relatively few patients receive antiretroviral therapy, and many suffer from debilitating diarrhea that affects their quality of life. Given the track record of probiotics to alleviate diarrhea, conventional yogurt fermented with Lactobacillus delbruekii var bulgaricus and Streptococcus thermophilus was supplemented with probiotic Lactobacillus rhamnosus GR-1 and L. reuteri RC-14. Twenty-four HIV/AIDS adult female patients (18 to 44 y) with clinical signs of moderate diarrhea, CD4 counts over 200, and not receiving antiretrovirals or dietary supplements, consumed either 100 mL supplemented or unsupplemented yogurt per day for 15 days. Hematologic profiles, CD4 cell counts, and quality of life was evaluated at baseline, 15 and 30 days postprobiotic-yogurt feeding. There was no significant alteration in the hematologic parameters of both groups before and after the probiotic-yogurt feeding. The probiotic yogurt group at baseline, 15 and 30 days had a mean WBC count of 5.8+/-0.76 x 10(9)/L, 6.0+/-1.02 x 10(9)/L, and 5.4+/-0.14 x 10(9)/L, respectively. However, the mean CD4 cell count remained the same or increased at 15 and 30 days in 11/12 probiotic-treated subjects compared to 3/12 in the control. Diarrhea, flatulence, and nausea resolved in 12/12 probiotic-treated subjects within 2 days, compared to 2/12 receiving yogurt for 15 days. This is the first study to show the benefits of probiotic yogurt on quality of life of women in Nigeria with HIV/AIDS, and suggests that perhaps a simple fermented food can provide some relief in the management of the AIDS epidemic in Africa.

NEW! Managing and Preventing HIV Med Side-Effects

To mark its fifth anniversary, the New York Buyers’ Club has prepared a special edition of SUPPLEMENT. In it you will find a concise Guide to managing and preventing HIV medication side effects with supplements and other complementary and alternative therapies.

This is an invaluable introduction to how nutritional supplements can be used to counter those side effects that can make life miserable–or even disrupt treatment adherence–in people taking antiretroviral medications for HIV.

Read about approaches to dealing with diarrhea, nausea, heart health issues, diabetes, insomnia, fatigue, liver stress, lipodystrophy, anxiety and depression.

This FREE Guide is available online at:

http://newyorkbuyersclub.org/

On the NYBC website you can also SUBSCRIBE to the nonprofit co-op’s quarterly FREE newsletter, THE SUPPLEMENT, which continues to offer a unique perspective on current evidence-based use of supplements for chronic conditions including cardiovascular disease, diabetes/insulin resistance, hepatitis and other liver conditions, anxiety/depression, osteoarthritis, cognitive and neurorological issues, and gastrointestinal dysfunction.