12.
The monoamine serotonin is synthesized mainly by enterochromaffin cells in the
intestine. A mouse was treated with broad range of antibiotics for a week. After a week,
both the diversity of gut microbiota and serum serotonin levels was reduced. In another
independent study, a co-culture of Lactobacillus and enterochromaffin cells induced
serotonin synthesis. Based on these observations, the reason for decreased serum
serotonin in antibiotic treated mouse would most likely be
a. Antibiotics inhibit serotonin synthesis
b. Gut microbiota play an important role in serotonin biosynthesis
c. Antibiotics make the mouse depressed and hence reduce the levels of serotonin
d. Antibiotics degrade serum serotonin

The correct answer is: b. Gut microbiota play an important role in serotonin biosynthesis.

Introduction: Gut Microbiota, Serotonin, and Antibiotics

Most of the body’s serotonin (about 90–95%) is synthesized in the gastrointestinal tract by enterochromaffin (EC) cells, which release serotonin into the gut and circulation to regulate motility and other physiological functions. Experimental studies in mice show that depletion of gut microbiota by broad-spectrum antibiotics leads to reduced colonic and serum serotonin, without loss of EC cell numbers, indicating that microbes regulate serotonin production rather than EC cell survival. Several gut bacteria, including Lactobacillus species, can stimulate EC cells and enhance 5‑HT (serotonin) secretion by upregulating pathways such as tryptophan hydroxylase 1 (TPH1), the rate‑limiting enzyme in serotonin biosynthesis.​

In the question, antibiotics decrease gut microbial diversity and serum serotonin, while co-culture of Lactobacillus with enterochromaffin cells induces serotonin synthesis. This points directly to a microbiota-dependent regulation of serotonin biosynthesis.

Stepwise Logical Analysis of the Question

1. Baseline fact: Serotonin is synthesized mainly in intestinal enterochromaffin cells.​

2. Observation 1: Broad-spectrum antibiotics for a week →

   • Decreased diversity of gut microbiota.

   • Decreased serum serotonin levels.​

3. Observation 2 (independent study): Co-culture of Lactobacillus with enterochromaffin cells → induced serotonin synthesis.​

4. Inference: Presence of certain gut bacteria (e.g., Lactobacillus) promotes serotonin synthesis by EC cells; removal of these bacteria (via antibiotics) reduces serotonin.​

Therefore, the most likely reason for decreased serum serotonin in the antibiotic-treated mouse is that gut microbiota are required to support normal serotonin biosynthesis, and when they are depleted, serotonin production falls.

Option-by-Option Explanation

Option (b): Gut microbiota play an important role in serotonin biosynthesis ✅ (Correct)

• Multiple studies show that germ-free or antibiotic-treated mice, which have depleted microbiota, exhibit significantly reduced colonic and serum serotonin levels, despite having similar numbers of enterochromaffin cells.​

• Gut bacteria produce metabolites such as short-chain fatty acids that stimulate TPH1 expression and 5‑HT synthesis in EC cells; colonization or exposure to bacterial products restores or enhances 5‑HT production.​

• Probiotics like Lactobacillus and Bifidobacterium strains have been shown to promote 5‑HT secretion from EC cells by modulating signaling pathways and tryptophan/TPH-related mechanisms.​

These findings match the question: antibiotics reduce microbiota and serotonin; Lactobacillus co-culture induces serotonin. Thus, option (b) is the only explanation consistent with the given experimental data and with known gut microbiota–serotonin crosstalk.​

Option (a): Antibiotics inhibit serotonin synthesis ❌ (Incorrect)

• The question does not state that antibiotics directly inhibit the enzymes of serotonin biosynthesis (such as TPH1) in host enterochromaffin cells.

• Most antibiotics target bacterial structures and processes—cell wall synthesis, protein synthesis (bacterial ribosomes), DNA replication, or specific bacterial enzymes—not host serotonin biosynthetic enzymes.​

• Experimental work specifically shows that when microbiota are depleted by antibiotics, EC cell numbers remain unchanged but 5‑HT content and TPH1 expression decrease, implicating loss of microbial signals, not direct enzymatic inhibition by the antibiotic on host cells.​

Thus, the primary effect is indirect via microbiota, not a direct biochemical block of serotonin synthesis enzymes, so option (a) is not the best explanation.

Option (c): Antibiotics make the mouse depressed and hence reduce the levels of serotonin ❌ (Incorrect / irrelevant mechanism)

• The question focuses on serum serotonin and gut enterochromaffin cells, not brain serotonin or behavioral state.​

• While the gut–brain axis links microbiota, mood, and central serotonergic signaling, the experimental design here measures peripheral/serum serotonin changes after microbiota depletion, which are readily explained by altered EC cell function.​

• Moreover, the question provides direct mechanistic evidence (Lactobacillus co-culture inducing serotonin in EC cells), making a psychological explanation unnecessary and unsupported by the given data.​

Therefore, invoking “depression” as the cause of reduced serum serotonin is speculative and does not align with the experimental observations, so option (c) is incorrect.

Option (d): Antibiotics degrade serum serotonin ❌ (Incorrect)

• There is no indication that common broad-spectrum antibiotics chemically degrade serotonin in the bloodstream.

• Known serotonin clearance is mainly via uptake into platelets and metabolism by monoamine oxidase, not by antibiotic-driven degradation.​

• The key pattern in the question is: antibiotics ↓ microbiota diversity + independent evidence that bacteria (Lactobacillus) can stimulate serotonin synthesis; this clearly points to regulation of production, not chemical destruction of serotonin already in serum.​

Hence, antibiotics are not acting as “serotonin-degrading agents,” and option (d) does not explain the results.

Mechanistic Insight: How Gut Microbiota Regulate Serotonin

• Site of production: Around 90–95% of body serotonin is produced in the gut by enterochromaffin cells.​

• Microbial metabolites: Short-chain fatty acids and other microbial factors enhance TPH1 expression and 5‑HT production in EC cells.​

• Effect of antibiotics: Broad-spectrum antibiotics reduce microbiota-derived signals, leading to lower colonic 5‑HT and reduced serum serotonin, as observed in antibiotic-treated mice.​

• Role of Lactobacillus: Certain Lactobacillus strains can promote EC cell serotonin secretion by activating specific receptor and signaling cascades, which is consistent with the co-culture experiment in the question.​

Thus, gut microbiota are integral regulators of serotonin biosynthesis, and their depletion by antibiotics is the most logical and experimentally supported reason for decreased serum serotonin in the mouse.

Final Answer: (b) Gut microbiota play an important role in serotonin biosynthesis.