The Gut Microbiome May Offer a Solution to Male Infertility

Sam Westreich, PhD

Research suggests the answer is yes. Is a probiotic going to be the long-awaited male birth control pill?

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“Husband, wait — did you remember to take your probiotic birth control pill?” “Yes, wife.”Womanizer Toys on Unsplash

Birth control and pregnancy are definitely hot-button topics these days. There’s a lot of debate about how we define life, who is in full control, and bodily autonomy. It’s a detailed discussion, so this article will skirt that issue.

Instead, let's talk about the frustrating fact that there’s no such thing as a male birth control pill. Men have options to prevent pregnancy, but they’re either use-it-every-time (condoms), or a more involved and permanent option (vasectomy).

Conversely, some couples are actively trying to get pregnant and face difficulties. Multiple studies have noted a worldwide decline in male sperm production over the last century, with many of them drawing connections to increased levels of pollution.

Since I’m a microbiome scientist by training, I like to believe that my area of study is incredibly important and all-encompassing. “Male fertility is probably a microbiome problem!” I confidently declare, basing my statement on nothing but the assuredness that, as a scientist, I am probably right.

But am I correct? Is there a link between the gut microbiome and male fertility — and infertility?

Surprisingly, the answer seems to be yes, although it’s still a topic of open research. But at least in mice, the solution to male infertility — and a tantalizing possibility of a male birth control pill — may reside with the bacteria living in the intestinal tract.

The gut microbiome, and how it has its grubby fingers in everything

First, let’s start with a brief overview of what we’re talking about when we refer to the gut microbiome.

The term gut microbiome refers to the collection of many different species of bacteria living inside your lower intestinal tract. This little rainforest of many different bacterial species, all living in a balance of cooperation and competition, lives as a passenger in our bodies — but its composition has effects on our own health.

Our microbiome impacts how we digest food and what nutrients we absorb from it, but its effects don’t stop there. It helps to train our immune system, teaching our immune cells what is dangerous and what is nonthreatening. It can contribute to our weight gain and loss, and the wrong microbes seem to promote obesity. It even produces neurotransmitters and hormones that can impact our mood and mental health. Even if you don’t like cats and dogs, you’ve got to care for your microbes.

One way that we first start to establish if there’s a link between the gut microbiome and a particular condition?

Take the microbiome out of the picture. When we take antibiotics, we are usually aiming to kill a dangerous pathogenic bacterial invader. But antibiotics are pretty broad-spectrum, wiping out all bacteria — friend or foe. Antibiotics annihilate our gut microbiome, and it may take days to weeks to recover.

What happens to male fertility after a round of antibiotics?

Depending on the specific type of antibiotic, the effects may vary, but it does seem to have a negative effect on male fertility. Antibiotics have been shown to reduce both the number of sperm, and their quality; they swim more slowly and erratically if the man is on an antibiotic regimen.

How could killing bacteria lead to lower sperm quality?

The answer is likely that the microbiome plays some contributory role in the production of sperm. When you temporarily destroy this through antibiotic consumption, you reduce the amount of produced proto-materials used to make sperm, and your sperm count and quality decreases.

New research suggests that the microbiome may be involved in certain chemical compounds used in sperm production. This opens up two potential avenues for intervention:

  • Want more sperm, because you’re trying to procreate? Add more of these chemicals, or more microbes that produce the chemicals.
  • Want fewer sperm, to avoid conceiving? Introduce blockers to these chemicals.

Here’s what the study found.

Polyamine metabolism links gut microbiota and testicular dysfunction

This study, published last year by researchers at the Chinese Academy of Sciences, looks at how the microbiome interacts with the testicular health of mice. The researchers used a chemical called triptolide to lower sperm production, and then examined the microbiome to see whether triptolide might be having effects on it that lead to the lowered sperm count.

(By the way, you wouldn’t want to take triptolide in order to act as a method of reducing your sperm count for birth control. It’s an anti-cancer drug, and also blocks the growth of many types of new cells. This leads to suppression of the immune system — not something we want in healthy adults! And because it causes such testicular toxicity, triptolide is very rarely used in humans at all.)

However, that testicular toxicity of triptolide can be negated by the right gut microbiome! It appears that certain types of bacteria in the gut microbiome are able to synthesize a particular compound called spermine.

Spermine is a molecule that our body naturally synthesizes; it helps to defend our DNA against free radicals that would damage it. It got its name because it was first isolated from sperm (in 1678!), but it’s present in all cells. Spermine can also be produced by several types of bacteria, many of which are present in our gut.

Why is spermine important? We don’t fully understand how triptolide causes damage to our testes and sperm production, but it appears to be through oxidative stress. And spermine, as a potent anti-oxidant, might be a great way to shield against this stress-induced damage.

When mice were fed triptolide, it not only caused oxidative stress, but it also altered the composition of the mouse gut microbiome, reducing the levels of bacteria that would produce the spermine anti-oxidant that could counteract that stress.

Furthermore, the researchers didn’t even need the triptolide to cause testicular stress. If they just provided the mice with antibiotics, it wiped out the mouse gut microbiome — and the sperm production suffered.

On the other hand, when researchers supplemented the mouse diet with spermine and other polyamines (related molecules), sperm production was restored back to normal levels! Even adding in spermine-producing probiotic bacteria was able to bring back better sperm production.

What conclusions can we take? How could this improve our lives?

Summing up what we’ve seen so far:

  • Some chemicals, like triptolide, can reduce sperm levels and quality. They do so by inducing oxidative stress.
  • These chemicals also disrupt the gut microbiome, blocking the microbiome’s production of anti-oxidative polyamines, like spermine.
  • Similarly, antibiotics kill off gut bacteria, lowering antioxidant levels and reducing sperm quality and levels.
  • Supplementing with either the right bacteria, or extra polyamines, helps restore normal sperm production and quality.

This could be a path to reversible, easily managed male birth control!

There’s still more research to be done, of course; this isn’t ready for human consumption. We don’t want to be constantly suppressing our immune system or constantly wiping out our gut microbiome, just to lower sperm levels.

But if we can find ways to limit the oxidative stress solely to the testes and block the uptake of antioxidants in that area, we’ve got a way to reduce fertility — that can be turned off at any time!

And for men with fertility problems, it may be due to oxidative stress. For these men, adding in either probiotic bacteria that produce antioxidant spermine, or directly adding antioxidants like spermine and other polyamines to the diet, could help improve fertility.

For right now, the best action for anyone looking to combat infertility is to avoid antibiotics. Some particular strains, such as Parabacteroides distasonis, have been noted as particular polyamine producers, but they are still being evaluated as a potential probiotic.

In the near future, we may be able to use specifically targeted oxidative stress to block male fertility — and probiotics to bring in the right gut bacteria to restore fertility. And when a couple conceives, they’ll need to give a shout-out to their tiny gut microbiome assistants!

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A microbiome scientist working at a tech startup in Silicon Valley, Sam Westreich provides insights into science and technology, exploring the strangest areas of biology, science, and biotechnology.

Mountain View, CA
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